By Ryan Duffy, 4th Year Neuroscience MSci

Inflammation is a biological process that is critical in the defence of an organism and enables repair and recovery from damage to tissues. Inflammation is very common, and it occurs in many different species including humans. Inflammation can occur when we damage part of our body either through impact, or through infection. Our immune system then recognises that there is damage to tissue or invasion of a bacteria and it causes blood and immune cells to rush to the site of injury, causing that painful, swollen, and red site of inflammation that we have all experienced. Once all the dead tissue/bacteria has been cleared up, the inflammation resolves and the immune cells disperse back into the blood, causing the swelling to go away (1). This process is normal, and it’s really helpful to prevent the damage from spreading to other parts of the body, as well as stop us from touching/using the damaged area so the immune cells can work their magic.

Like many biological processes you can have too much of a good thing, and the same is true for inflammation. In many neurological diseases, we see chronic inflammation that can lead to overactivation of the immune system. In these cases an overactive immune system can lead to autoimmune reactions, which means our body is actually attacking itself (2). To get around this issue, researchers have started to understand the components behind inflammation, and deepen our knowledge on the good, the bad, and the ugly of this double-edged sword.

Inflammation can also occur in the brain, in this case it is considered “neuroinflammation”, which molecularly is very similar to peripheral immune inflammation, however, in the brain neuroinflammation is mediated by specialised central nervous system (CNS) immune cells, known as microglia. As the name suggests, microglia are very small cells that survey our CNS, becoming activated when a threat is detected, such as tissue damage. In this context, the microglia release inflammatory mediators to induce neuroinflammation, which starts the process of tissue repair (3).

In many diseases, neuroinflammation can have a neuroprotective role and prevent further damage from occurring. The most common example of this is in stroke. During a brain bleed, microglia can become active to clear hematoma’s and dead tissue, which has a neuroprotective role, in a “cut your losses” type mechanism (4). However, also in stroke the same mechanism can be detrimental to the patient in cases of prolonged inflammation. If microglia sustain neuroinflammation after the damaged tissue has been removed, they can begin to remove healthy tissue, in a process called autoimmune damage, meaning the microglia have mistaken the healthy tissue for damaged tissue, leading to devastating changes to the brain, and therefore, leading to disability in many stroke patients (5).

Knowing this, we can start to see that neuroinflammation isn’t the problem in this disease, but it is the timing and level that determines if this immune interaction is protective or detrimental to brain tissue. So how can we treat a mechanism that is helping one minute and hindering the next? One-way researchers have tried to do this is through the use of stem cells, which have shown promising results for patients suffering from detrimental neuroinflammation post stroke. Stem cells have been effective due to their anti-inflammatory, anti-oxidative, and anti-apoptotic factors, meaning they guard against neuroinflammation and can prevent damage to healthy tissue (6). Stem cells have also been shown to have neurogenitive effects, meaning they also permit the growth of new tissue, improving the recovery and maintaining cognitive function in stroke patients. It is possible that in the future, stems cells could be used in conjunction with other medications to give patients suffering from neuroinflammatory disorders the best chance of recovery.

References

1. Collier M. Understanding wound inflammation. Nurs Times. 2003 Jun;99(25):63–4.
2. Terrando N, Pavlov VA. Editorial: Neuro-Immune Interactions in Inflammation and Autoimmunity. Front Immunol [Internet]. 2018;9. Available from: https://www.frontiersin.org/articles/10.3389/fimmu.2018.00772
3. Muzio L, Viotti A, Martino G. Microglia in Neuroinflammation and Neurodegeneration: From Understanding to Therapy. Front Neurosci [Internet]. 2021;15. Available from: https://www.frontiersin.org/articles/10.3389/fnins.2021.742065
4. Dabrowska S, Andrzejewska A, Lukomska B, Janowski M. Neuroinflammation as a target for treatment of stroke using mesenchymal stem cells and extracellular vesicles. J Neuroinflammation [Internet]. 2019;16(1):178. Available from: https://doi.org/10.1186/s12974-019-1571-8
5. Lian L, Zhang Y, Liu L, Yang L, Cai Y, Zhang J, et al. Neuroinflammation in Ischemic Stroke: Focus on MicroRNA-mediated Polarization of Microglia. Front Mol Neurosci [Internet]. 2021;13. Available from: https://www.frontiersin.org/articles/10.3389/fnmol.2020.612439
6. Tuazon JP, Castelli V, Borlongan C V. Drug-like delivery methods of stem cells as biologics for stroke. Expert Opin Drug Deliv. 2019 Aug;16(8):823–33.

The post Neuroinflammation: the doubled edged sword of the brain appeared first on School of Life Sciences.

By Argyro Philippidou, 3^rd Year Neuroscience BSc

As a professional dancer and a soon to be neuroscientist, it would be inevitable that my passion for dance and movement collide with my drive for how the brain works. Moving to a beat, jiving, locking, and grooving on the dancefloor helps heal a person both physically and mentally. Most  dancers may agree that dancing for them is a soothing escape, a pause that transports you in a room full of blank canvases where you are the artists, and the paint is your emotion let out as dance moves.

Study conducted by the Albert Einstein college of medicine in 2003 suggests that dance is very beneficial for the brain and how it develops but also in how it supports our entire body during disease (Verghese et al., 2003). More specifically it has been found to be very helpful for treating or preventing neurodegenerative disorders such as Parkinson’s disease (PD) (Hackney et al., 2007) as well as dementia (Verghese et al., 2003).  In fact, out of all activities tested in 2003 study, to see how each impacts our brain’s health state, such as cycling, swimming, golf, tennis, only dancing has shown a possible clinical prevention in developing neurodegenerative diseases. More specifically, Tango as seen in Hackney’s study in 2007, has been a pivotal step in managing motor symptom deficits in PD. The synchronised coordination of movements tuned to music offers our brains what might be seen as a ‘healthy glow’.

Parkinson’s Disease is a neurodegenerative disorder which negatively affects motor and emotional stability as well as the quality of life of patients (Sharp and Hewitt, 2014). Research from Westheimer, 2008, reported that PD patients who attended dance classes regularly, have seen a great impact and positive inclination in their quality of life after completing a quality-of-life assessment questionnaire (Westheimer, 2008). Moreover, other study has also shown that dance classes also improved motor function in PD patients (Suchowersky et al., 2006).

How dance affects the brain in this positive manner may be explained by the “Synchronicity hypothesis of dance” (Basso, Satyal and Rugh, 2021):

“Dance enhances neural synchrony in brain regions supporting seven neurobehavioral areas: sensory, motor, cognitive, social, emotional, rhythmic, and creative.” (Basso et al., 2021)

In summary, dance helps PD patients both emotionally and physically. Unfortunately, there is not enough research in this field for dance to be used as a therapeutic agent or even for slowing down the onset symptoms of PD. For scientists and researchers to reach such conclusion, such studies must be ongoing for years, from childhood and adolescence until the age of the onset of the disease. Future studies would also have to consider gene expression and how it might change over time and through dancing. For now, dance is only seen as a rehabilitation technique which allows PD patients a sense of relief from their physical and psychological pain, which, for a neurodegenerative disease with no direct cure is what these patients seek the most.

Bibliography:

• Basso, J.C., Satyal, M.K. and Rugh, R. (2021). Dance on the Brain: Enhancing Intra- and Inter-Brain Synchrony. Frontiers in Human Neuroscience, [online] 14. doi:https://doi.org/10.3389/fnhum.2020.584312.
• ‌Burzynska A. Z., Finc K., Taylor B. K., Knecht A. M., Kramer A. F. (2017). The dancing brain: structural and functional signatures of expert dance training.  Hum. Neurosci.11:566. 10.3389/fnhum.2017.00566
• Hackney, M.E., Kantorovich, S., Levin, R. and Earhart, G.M. (2007). Effects of Tango on Functional Mobility in Parkinson’s Disease: A Preliminary Study. Journal of Neurologic Physical Therapy, [online] 31(4), pp.173–179. doi:https://doi.org/10.1097/npt.0b013e31815ce78b.
• Sharp, K. and Hewitt, J. (2014). Dance as an intervention for people with Parkinson’s disease: A systematic review and meta-analysis. Neuroscience & Biobehavioral Reviews, [online] 47, pp.445–456. doi:https://doi.org/10.1016/j.neubiorev.2014.09.009.
• Suchowersky, O., Gronseth, G., Perlmutter, J., Reich, S., Zesiewicz, T. and Weiner, W.J. (2006). Practice Parameter: Neuroprotective strategies and alternative therapies for Parkinson disease (an evidence-based review): [RETIRED]. Neurology, [online] 66(7), pp.976–982. doi:https://doi.org/10.1212/01.wnl.0000206363.57955.1b.
• ‌ Verghese, J., Lipton, R.B., Katz, M.J., Hall, C.B., Derby, C.A., Kuslansky, G., Ambrose, A.F., Sliwinski, M. and Buschke, H. (2003). Leisure Activities and the Risk of Dementia in the Elderly. New England Journal of Medicine, [online] 348(25), pp.2508–2516. doi:https://doi.org/10.1056/nejmoa022252.
• Westheimer, O. (2008). Why Dance for Parkinson’s Disease. Topics in Geriatric Rehabilitation, [online] 24(2), pp.127–140. doi:https://doi.org/10.1097/01.tgr.0000318900.95313.af.

The post Dancing to defy Parkinson’s Disease appeared first on School of Life Sciences.

By Argyro Philippidou, 3^rd Year Neuroscience BSc

I came across this treatment technique this summer during my internship. It’s called TMS which stands for Transcranial Magnetic Stimulation. What it does it sends magnetic pulses through a handheld controller which is projected on the designated brain region a scientist would want to stimulate. So how could this help in treating Alzheimer’s disease?

Firstly, TMS has been a topic of investigation for decades now. It is a non-invasive neurorehabilitation tool that has been shown to improve cognition in patients with Alzheimer’s (Zhao et al, 2017). Although it sounds like a complex technique, in actuality its basic concept is very simple. Think of it like drinking too much water at once, at first you might feel a bit nauseous but then everything eventually balances out and you feel better. In corelation to science, it stimulates areas of the brain influenced by Alzheimer’s disease, like the hippocampus the entorhinal cortex and the precuneus, even more than they are usually active, thus enhancing the activation of neurons in the brain. However, then it causes the reestablishment of balance of neurotransmitters such as glutamate (Olajide OJ. Et al., 2021), the decrease of reactive oxygen species (Bhat S. et al, 2021) and neuroinflammation (Hur JY et al., 2020) as well as the decrease of the primary constitute of Alzheimer’s the misfolding and aggregation of tau proteins (Udin MS. Et al., 2020). By affecting all these internal brain mechanisms, it also improves the main cognitive deficit of Alzheimer’s, memory decline.

There are many types of memories including working memory, episodic memory, semantic memory, long term memory and short-term memory. Alzheimer’s disease primarily affects episodic memory. This type of memory consists of information from recent or past events. Therefore, people with Alzheimer’s disease have difficulty in recalling events from the past. Pharmacological treatments have not yet been evidently successful in improving episodic memory alone.

2022 Study conducted at the University of Technology in Cyprus by Artemis Traikapi has shown that TMS treatment improved episodic memory recall of Alzheimer’s patients up to 3 months post treatment (Traikapi A et al., 2022). Patients’ memories were assessed and compared before and after TMS treatment using “word learning and logical memory tests” (Traikapi A., et al., 2022). Both tests and all psychological assessments had improved up to 3 months post TMS treatment. This type of treatment also subsided patients’ anxiety symptoms associated with the disease (Traikapi A. et al, 2022). More research however has to be done as only 4 patients represent these results and although significant, a greater population of Alzheimer patients has to be reached out and tested in order for TMS to establish its reliable reputation.

Although TMS is not always suitable for all people, for example for people with a genetic predisposition to epileptic seizures or people that have had epileptic episodes before. However, for patients that have no epileptic risk and are in need of TMS therapy, side effects are very minimal to none and lately TMS has also been used to treat patients with other neurological and mental diseases such as depression (Mussigmann et al., 2021) and chronic pain (Fitzgerald & Watson, 2018). This non-invasive neurorehabilitation treatment can therefore open new therapeutic doors for patients who decide to take a non-pharmacological route.

References:

• Bhatt S, Puli L and Patil CR: Role of reactive oxygen species in the progression of Alzheimer’s disease. Drug Discov Today. 26:794–803. 2021. View Article: Google Scholar : PubMed/NCBI
• Fitzgerald, P. J., & Watson, B. O. (2018). Gamma oscillations as a biomarker for major depression: An emerging topic. Translational Psychiatry, 8(1), 1–7. https://doi.org/10.1038/s41398-018-0239-y
• Hur JY, Frost GR, Wu X, Crump C, Pan SJ, Wong E, Barros M, Li T, Nie P, Zhai Y, et al: The innate immunity protein IFITM3 modulates γ-secretase in Alzheimer’s disease. Nat Aust. 586:735–740. 2020. View Article: Google Scholar : PubMed/NCBI
• Mussigmann, T., Lefaucheur, J. P., & McGonigal, A. (2021). Gamma-band activities in the context of pain: A signal from brain or muscle? Neurophysiologie Clinique, 51, 287–289. https://doi.org/10.1016/j.neucli.2021.03.007
• Olajide OJ, Gbadamosi IT, Yawson EO, Arogundade T, Lewu FS, Ogunrinola KY, Adigun OO, Bamisi O, Lambe E, Arietarhire LO, et al: Hippocampal degeneration and behavioral impairment during Alzheimer-like pathogenesis involves glutamate excitotoxicity. J Mol Neurosci. 71:1205–1220. 2021. View Article: Google Scholar : PubMed/NCBI
• Traikapi, A., Kalli, I., Kyriakou, A., Stylianou, E., Symeou, R.T., Kardama, A., Christou, Y.P., Phylactou, P. and Konstantinou, N. (2022). Episodic memory effects of gamma frequency precuneus transcranial magnetic stimulation in Alzheimer’s disease: A randomized multiple baseline study. Journal of Neuropsychology. [online] doi:10.1111/jnp.12299.
• Uddin MS, Al Mamun A, Rahman M, Behl T, Perveen A, Hafeez A, Bin-Jumah MN, Abdel-Daim MM and Ashraf GM: Emerging proof of protein misfolding and interactions in multifactorial Alzheimer’s disease. Curr Top Med Chem. 20:2380–2390. 2020. View Article: Google Scholar : PubMed/NCBI

The post A non-pharmacological approach to treating Alzheimer’s Disease appeared first on School of Life Sciences.

By Argyro Philippidou, 3^rd Year Neuroscience BSc

Hyperbaric oxygen treatment (HBOT) is not a treatment you commonly or routinely hear. It actually has the potential to be an alternative therapy to any disease in which cell regeneration and decrease of inflammation are the therapeutic targets. A close person of mine has undergone HBOT for their chronic pain ailment, trigeminal neuralgia, and that is how I stumbled across it. Once I had heard about it and researched HBOT, I felt that this is an alternative therapy that people ought to know more about. It is painless and almost effortless- except if one may consider breathing an effortful action. Patients with chronic pain may therefore prefer this kind of therapy compared to classic chronic pain treatments such as antidepressants, muscle relaxants and anti-epileptic drugs which come with a package of side effects.

Establishing  the basic mechanism of chronic pain is therefore crucial to understand  how such a therapy may be useful and the multidisciplinary approach taken to treat chronic pain syndromes. Chronic pain is defined as a pain response that usually lasts over a period of 3 months either persistently acting or recurrently acting (Treede R et al., 2015). Chronic pain is tightly paired with the word maladaptive amongst scientists. In this case, chronic pain disrupts the physiological pain actions and processes of our body making it incapable of adapting to our normal processing of sensory stimuli and thus adopts a maladaptive nature. Such physiological pain processes consist of the regulation of substances called neurotransmitters and inflammatory mediating substances like interleukin 1β and TNF-alpha (Yildis S et al.,2006), in both the Central nervous system which consists of the brain and spinal cord as well as the peripheral nervous system that consists of the nerves that branch out from our brain and spinal cord and reach the rest of the body.

HBOT has been a pivotal step for over 40 years now (Leach RM. Et al., 1998) in treating sea divers from the rapid change in pressure and its physiological effects like decompression sickness, it has on their bodies. Nowadays research suggests that HBOT can also treat chronic pain syndromes such as chronic headaches, fibromyalgia as well as trigeminal neuralgia (Sutherland AM. et al, 2015). HBOT allows patients to breathe 100% oxygen at very high pressures than we are used to. This allows oxygen to travel in plentiful amounts in all areas of our body that need it including blood and lungs. This spreading of oxygen allows the body to restore itself (Thom SR., 2011) and eliminate chronic pain scales by reducing inflammation in each patient’s designated painful area. This has been proven in both animal and human studies by researchers in the university of Toronto (Sutherland AM. et al, 2015). In fact, it can decrease pain responses up to 80-95% for up to 90 mins after HBO therapy (Zelinski LM et al., 2009). Inflammatory substances causing pain like interleukin 1β and TNF-alpha are significantly decreased as studies by Yildis S et al. 2006 have shown (Yildis S et al., 2006)

Unfortunately, HBO comes in when conventional treatments fail.  Pharmacological approaches although not always the best option, seem to be the research field where more funding is placed in and thus marketing and promotion of those drugs as well as high sales rates is what pharmaceutical companies prefer and indirectly demand. We must take into consideration how exposure to different pain relief drugs may alter the effect of HBOT on patients with chronic pain. Many fore coming studies should consider these factors when treating patients with HBO treatment. However, it is an ever more promising alternative to the traditional and dated pharmacological approach to treating chronic pain syndromes.

References:

• Leach, R.M., Rees, P.J. and Wilmshurst, P. (1998). ABC of oxygen: Hyperbaric oxygen therapy. BMJ, 317(7166), pp.1140–1143. doi:10.1136/bmj.317.7166.1140.
• Sutherland, A.M., Clarke, H.A., Katz, J. and Katznelson, R. (2015). Hyperbaric Oxygen Therapy: A New Treatment for Chronic Pain? Pain Practice, [online] 16(5), pp.620–628. doi:10.1111/papr.12312.
• Thom SR. (2011) Hyperbaric oxygen: its mechanisms and efficacy. Plast Reconstr Surg. ;127(Suppl 1):131S–141S.
• Treede, R.-D., Rief, W., Barke, A., Aziz, Q., Bennett, M.I., Benoliel, R., Cohen, M., Evers, S., Finnerup, N.B., First, M.B., Giamberardino, M.A., Kaasa, S., Kosek, E., Lavand’homme, P., Nicholas, M., Perrot, S., Scholz, J., Schug, S., Smith, B.H. and Svensson, P. (2015). A classification of chronic pain for ICD-11. Pain, [online] 156(6), pp.1003–1007. doi:10.1097/j.pain.0000000000000160.
• Yildiz, S., Uzun, G. and Kiralp, M.Z. (2006). Hyperbaric oxygen therapy in chronic pain management. Current Pain and Headache Reports, [online] 10(2), pp.95–100. doi:10.1007/s11916-006-0019-x.
• ‌Zelinski LM, Ohgami Y, Chung E, Shirachi DY, Quock RM. (2009) A prolonged nitric oxide-dependent, opioid- mediated antinociceptive effect of hyperbaric oxygen in mice. J Pain.;10:167–172.

The post Breathing oxygen may be the new treatment for chronic pain appeared first on School of Life Sciences.

By Ryan Duffy, 4th Year Neuroscience MSci

Opioids are a class of drugs that interact with the endogenous opioid system, to either activate or deactivate its impact on bodily sensations or psychological states. Endogenous means that our body must make compounds that activate this system, and indeed they do. Endorphins is one of the major opioids released from the body, and many studies believe it is the compounds that leads to “runners high”, as endorphins are release during physical activity (1). Learning about the interconnectivity of the endogenous opioid system, neuroscientists found compounds that we don’t make naturally that can also activate opioid receptors. The major opioid drug used in hospitals around the world, morphine, was first isolated from opium in the early 1800’s and it was quickly introduced into clinical practice.

The main function of opioids is in a pain killer, and it remains the most effective pain killer to date. Morphine works by activating opioid in the central nervous system (brain and spinal cord) and the peripheral nervous system (nerves). When they activate this receptor, they “turn off” neurons, and prevent their activity, making morphine a central nervous system depressant. Turning off the nervous system is an incredibly effective pain-relieving tool as it prevents the nerves from conducting painful signals to the brain, meaning, no “pain” can be perceived.

With all drugs there is normally an equal exchange between value and side effects, and morphine is no different. Because morphine is so good at shutting down neuronal activity, if too much is used, we can start to shut down processes that we want to keep “on”. The most common of these processes is breathing, more specifically contraction the muscles we use to breath. Because morphine relaxes the nerves so much it can prevent the automatic breathing process that is normally taken care of by the brain when we fall asleep. This leads to a condition called respiratory depression, and it the most common cause of death associated with opioid overdose (2).

Not only do opioids have serious side effects, but they are also highly addictive. One of the reasons for this is because they activate the brains “reward pathway”. By activating the reward pathway, we can significantly increase in dopamine, which is a chemical that is thought to regulate emotion, motivation, and reward. When the drug wears off, we also lose the dopamine that it increased, and we also see that dopamine goes below baseline as the body doesn’t produce as much as it normally would in healthy conditions. This lowering in normal dopamine is theorised to be one of the reasons why psychological withdrawal occurs and addiction begins (3).

Because of these addictive qualities opioid based medications have become drugs of abuse, particularly in north America, where many experts are terming mass opioid abuse as a epidemic. In the US 3,000,000 citizens suffer from opioid use disorder, with 500,000 of these being addicted to heroin. With these statistics being so profound, should be thinking about altering opioid use to treat pain?

One problem that has been identified by experts is the over reliance on opioids to treat mild to moderate pain, in combination with a lack of transparency from drug companies regarding the addictive qualities of opioids. The first drug to light the fuse on the epidemic was called Oxycodone (OxyContin), a semi-synthetic opioid that was initially intended to be used a pain killer for moderate pain like a migraine. The problem with this drug was that it was described and sold to doctors as non-addictive, and advertising campaigns signalled that the drug had a less the 1% addiction rate. Because of this, doctors were more willing to give OxyContin to patients as a first line pain killer, as it was effective and “non-addictive”. It soon came out that OxyContin was much more additive and dangerous than first imagined, in fact, it was found that OxyContin was just as addictive as other opioid medication like morphine. Because of this, patients that took OxyContin regularly became addicted to opioids. With continued use their tolerance grew too, meaning they needed a higher dose to achieve the same pain-relieving effect, which is another common side effect of opioids. Because of the price of OxyContin many users couldn’t afford to increase their dose and they swapped to other opioids that were cheaper like heroin or fentanyl, to reach the same concentration and therefore the same pain relief (4).

Suggestions to rectify this situation have included education to aware healthcare professionals and patients of the dark side of opioids, in an attempt to prevent over prescription and abuse. The enhancement of non-opioids drugs as first as painkillers and the use of opioids is reserved for severe pain.

Although a lot of damage has been done with these drugs, it is important to be hopeful and use these tragedies as lessons for the rest of the world. Implementing these as standard procedures before it becomes a worldwide opioid pandemic.

1. Hicks SD, Jacob P, Perez O, Baffuto M, Gagnon Z, Middleton FA. The Transcriptional Signature of a Runner’s High. Med Sci Sports Exerc. 2019 May;51(5):970–8.
2. Baldo BA, Rose MA. Mechanisms of opioid-induced respiratory depression. Arch Toxicol. 2022 Aug;96(8):2247–60.
3. Kosten TR, George TP. The neurobiology of opioid dependence: implications for treatment. Sci Pract Perspect. 2002 Jul;1(1):13–20.
4. Kibaly C, Alderete JA, Liu SH, Nasef HS, Law P-Y, Evans CJ, et al. Oxycodone in the Opioid Epidemic: High “Liking”, “Wanting”, and Abuse Liability. Cell Mol Neurobiol. 2021 Jul;41(5):899–926.

The post The highs and lows of opioid use: learning from the north American opioid epidemic appeared first on School of Life Sciences.

By Ryan Duffy, 4th Year Neuroscience MSci

Psychedelics are type of illicit drug that known to trigger alter states of consciousness, and the user may experience “trips”. In 1973, psychedelic substances were placed as a schedule 1 substance, meaning that the intriguing nature of psychedelics could not be explored by scientists as they were deemed to have no medical application or health benefits. This legislation prevented scientists from exploring how psychedelics worked and then to assess the extent of their utility in a clinical setting.

This has been the case until recently as certain neuroscience research groups have obtained special licenses to study how psychedelics work in humans and explore the idea that these mind-bending chemicals may have a place in medicine after all. The majority of these licenses have been provided to study psylocibin, which is the active ingredient that can be found in magic mushrooms. It is thought that psylocibins main mechanism is through activation of serotonin (5-HT2a) receptors, which are found all throughout the brain. Because of this, many scientists believe that psylocibin may be able to treat depression as a lot of current medications like fluoxetine also change the way the brain activates serotonin receptors.

Serotonin receptors in a healthy brain become active when serotonin is present. When active these receptors are thought to help maintain a person’s mood and mental well-being. One theory of depression speculates that depression may be caused by low concentrations of serotonin in the brain and therefore the serotonin receptors can’ be activated in the same healthy way (1). Without activation the brain has no way to correctly regulate mood and people can quickly fall into states of poor mental health with depressive symptoms being the most common. Pharmacological studies have shown that psylocibin has the ability to activate serotonin receptors (2) and can act as artificial serotonin to boost brain activate causing a reduction in depressive symptoms.

A recent investigation into this pharmacological phenomenon, involved a drug trial 233 patients across 10 countries, who all suffered from treatment-resistant depression, meaning that at least standard 2 medications hadn’t helped relief depressive symptoms. At the end of the trial 1 in 3 patients reported a significant reduction in depression and 1 in 5 said that the improvement lasted at least 12 weeks. In this trial, participants took a synthetic form of psylocibin whilst being guided through the psychedelic with a psychotherapist as many of the short-term hallucinogenic effects can be unnerving. The psychedelic trip can last anywhere up to 8 hours, and at the end of session many participants noted a mental clarity and that their depressive symptoms subsided (3).

In the UK, around 1 million adults don’t respond to first line treatment, so there is a real need for a fresh approach to depression and psychedelic assisted therapy may be the answer. To get further clarity on the utility of psylocibin another larger study has been planned following these positive results that will attempt to investigate how often the drug needs to be taken to provide anti-depressant benefits. If it is proven at this stage to be effective and safe, the drug could be taken to wide scale clinical trials, and we could see psylocibin assisted therapy become a treatment provided in the clinic within 5 years.

References

1. Delgado PL. Depression: the case for a monoamine deficiency. J Clin Psychiatry. 2000;61 Suppl 6:7–11.
2. López-Giménez JF, González-Maeso J. Hallucinogens and Serotonin 5-HT(2A) Receptor-Mediated Signaling Pathways. Curr Top Behav Neurosci. 2018;36:45–73.
3. Goodwin GM, Aaronson ST, Alvarez O, Arden PC, Baker A, Bennett JC, et al. Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. N Engl J Med. 2022;387(18):1637–48.

The post Psychedelic Therapy: Unlocking an Alternative Path to Treating Depression appeared first on School of Life Sciences.

Neuroscience is a complex and ever-growing field of science, requiring constant research to understand how the brain functions. We will never completely understand every aspect of the brain, but there is a great effort from the scientific community to expand our knowledge of such a complex but fascinating subject.

A large portion of the research within the School of Life Sciences is dedicated to enhancing the knowledge around the brain and its functions, including developing new techniques to observe the molecular systems within the brain. The brain is so densely packed with a large variety of different cells and chemical compounds, from various forms of neuronal cells to a vast array of different neurotransmitters, which makes it very important to have a definitive method of identifying each one. As more discoveries emerge, this becomes increasingly necessary to improve the accuracy of new studies.

One recent subject of interest is the compound 5-hydroxymethylcytosine (5hmC).  As well as being an intermediate in the DNA demethylation process [1], 5hmC is thought to also work as a stable epigenetic marker to regulate gene expression [2]. DNA demethylation leads to the activation of associated genes, so the presence of this intermediate cytosine form could be considered a marker for gene activation. 5hmC has been found to be abundant in neuronal cells in the brain, and thus could play an important part in gene expression within the central nervous system [3]. Due to its potentially crucial role in the nervous system, 5hmC has undergone much research to determine its exact functions, but also to find an effective way to analyse it within the brain.

In the School of Life Sciences, studies by Marcus Willis and Rebecca Trueman have outlined a definitive method to visualise 5hmC in the neuronal cells of rodents by using immunohistochemistry [3]. Immunohistochemistry is an important methodology that is utilised in many biological sciences as a way to image specific molecules or cells within the body using antibodies. In the protocol, Willis and Trueman used primary antibodies that bind to 5hmC on prepared brain segments, then secondary antibodies with a fluorescent marker attached. These secondary antibodies are bred against the animal the primary antibodies were developed in, causing them to bind to the primary antibodies attached to any 5hmC present. The brain segments are then able to be imaged using a specialised fluorescence microscope, allowing the concentrations of 5hmC to be visualised due to the fluorescent marker on the secondary antibodies.

Despite immunohistochemistry being relatively less quantitative than other methods of imaging, it is very specific and can be adapted to measure fluorescence levels to determine a quantitative concentration of the substance [3]. This methodology is utilised in a large variety of studies, including animal models of central nervous system disorders. For example, 5hmC is currently being investigated for its potential importance in the development of Alzheimer’s Disease [4]. High levels of 5hmC have been found to aid in the survival and continued function of neurons [4], so 5hmC could be implemented as a drug target to help relieve some symptoms for those with Alzheimer’s Disease. Protocols such as those outlined by researchers in the School of Life Sciences are critical to investigating and developing these types of novel treatments.

Image by Simon Litherland from University of Nottingham Image Bank

References

The post Immunohistochemistry in Neuroscience appeared first on School of Life Sciences.

Cognition is the combination of many mental processes that lead to the acquisition of knowledge or understanding. This can include the functions of conceptual understanding, reasoning, written and verbal communication, problem solving, memory, attention, and participation in the community [1]. Cognitive functions are obviously very important in everyday activities, however there are many conditions in which there are notable cognitive impairments that can severely disrupt day-to-day life for the sufferers. In recent times there has been many developments in this field, including important breakthroughs from the School of Life Sciences, that have brought us one step closer to a potential treatment for those dealing with cognitive impairment.

One condition that causes this cognitive decline is Alzheimer’s disease, a neurodegenerative disease that causes lesions and degradation within the brain [2]. Alzheimer’s disease is the most prevalent form of dementia, with up to 50 million people suffering worldwide with the condition [3]. Patients show significant cognitive deficits that worsen with age, particularly loss of memory [2], which can cause great distress for both the sufferer and their loved ones.

Autism spectrum disorder (ASD) is a neurodevelopmental condition that is characterised by social difficulties, including problems with communication and interactions [4]. A significant proportion of people with ASD also show regression of cognitive skills at a young age, such as language and communication, that continue into adulthood [4]. As the name suggests, there is a spectrum of different presentations of symptoms across all people with ASD, however some autistic people do suffer more than others and those with severe forms of ASD can show profound cognitive disabilities [5].

Although less recognised by the general public, schizophrenia also has a large cognitive component that can cause a significant impact to the patient’s life. Schizophrenia is a psychiatric condition that causes delusions, hallucinations, and psychosis. Despite most people only think of these so called ‘positive’ symptoms, a large aspect of schizophrenia is the ‘negative’ symptoms, which includes social cognitive deficits [6]. Schizophrenia can cause dementia like symptoms such as verbal memory and attention loss, so much so that it was originally called ‘dementia praecox’ [7]. These social cognitive impairments can lead to poor functioning within communities due to lack of emotional recognition, and the dementia-like symptoms can cause general disability and lack of independence [6].

Cognitive impairment can lead to a significantly reduced quality of life for the sufferer. It can massively affect the patients ability to live independently; for example, the severe loss of memory and recognition in Alzheimer’s patients can be dangerous for those living alone, especially in the later stages of the disease. So, with our ever-growing population, it is important that a treatment is identified for patients with cognitive decline. Potential drug therapies to improve the symptoms of cognitive impairment in patients with many of the conditions mentioned could help a significant proportion of the population live a more fulfilling life.

A recent study from the School of Life Sciences, led by Professor Kevin Fone, has highlighted a potential drug mechanism and target that could help in the treatment of patients with cognitive impairment [8]. The study focused on NMDA receptors as a drug target and compared the efficacy of drugs targeting the binding of the neurotransmitter glycine on these receptors. NMDA has an extremely important role in cognition and mood regulation, with levels notably lowered in schizophrenia patients, so acting on this receptor could show promising results in helping patients with cognitive decline. They found that glycine reuptake inhibitors and partial agonists of glycine were the most effective drugs for increasing cognitive abilities in rats with induced cognitive impairment. The rats given these experimental compounds showed an improved performance in novel object recognition and social recognition tasks. In additional studies, drugs such as the ones in this experiment have been found to be potentially useful in many conditions that cause cognitive impairment, such as Alzheimer’s disease, ASD, schizophrenia and even Parkinson’s disease.

Although this is not an exact cure to any of the conditions, it is a step in the right direction. This gives the potential for people with cognitive impairment to have an improved quality of life and could allow for greater independence despite their condition.

People with cognitive impairment show dysfunction in many aspects of life through no fault of their own, but new discoveries may be able to aid them in this struggle.

Image by ElisaRiva from Pixabay 

References

The post New research from the School of Life Sciences shows promise in the fight against cognitive decline appeared first on School of Life Sciences.

Written by Emma Gow, 3rd Year Neuroscience BSc

Anxiety is a relatively common disorder that normally affects around 5% of people in the UK [1], which appears to have increased due to the introduction of a national lockdown during the current COVID-19 pandemic [2]. These circumstances present us with the challenge of ensuring that we take our mental health seriously and work towards improving our mental wellbeing, as long-term anxiety can have a great toll on our overall heath. High levels of anxiety have been found to cause acute high blood pressure [3], consequently leading to an increased risk of stroke or heart disease [4]. Along with the obvious personal risk, there are also newly discovered long-term effects of prolonged anxiety that could affect the population in the near future.

A recent study from the School of Life Sciences has uncovered that high anxiety levels can affect the way we experience chronic pain [5]. In the study they focus on osteoarthritis, a condition affecting over 9 million elderly people in the UK [6] which causes severe chronic pain of the joints and ultimately a level of disability due to this pain [5].

The study looked at the effect of anxiety in the perception of this chronic pain and whether pre-existing anxieties have any effect on the severity of osteoarthritis that develops later in life. Using a cohort of people over the age of 40 gathered from the community, they established the level of anxiety the participants were suffering from using a self-assessed questionnaire. They were then separated into groups of those suffering from osteoarthritic knee pain and those who were pain free. Selected participants from each group underwent quantitative sensory testing to establish the level of pain they were feeling at various points on their leg by measuring their pain thresholds using a mechanical stimulus.

After analysing the data, they found that the pain thresholds were lower in the osteoarthritis group compared to the pain free group, meaning that they felt pain at a lower pressure. They also found that the overall anxiety scores were higher in the osteoarthritis group compared to the pain free group. The two factors of anxiety and lowered pain threshold were significantly correlated in the osteoarthritis group but not in the pain free group, which suggests that anxiety levels do affect the level at which we feel pain, especially with chronic conditions such as osteoarthritis.

The participants also took part in a follow up study a year later to assess their level of knee pain. The results of this follow up indicated that high anxiety scores in the initial assessment led to increased levels of knee pain, and were able to predict the onset of osteoarthritis after a year. Therefore, this study suggests that persistent anxiety could lead to future health problems having a greater impact when they develop and could accelerate the onset of these chronic conditions. Despite this being novel research, it highlights some very important secondary effects of anxiety which will become more apparent with further research.

Chronic pain is a major public health problem, causing significant economic and social impacts [7]. It is estimated that chronic pain costs the UK economy up to £11 billion [8], with that mostly being due to costs of treatment and work absences. This shows that we need to put great importance on the nation’s mental health struggles at this time as ignoring the problem at hand may lead to increased complications in the years to come, and potentially worsen an already struggling economy.

References

[1] NHS, “Overview: Generalised anxiety disorder in adults,” NHS, December 2018. [Online]. Available: https://www.nhs.uk/conditions/generalised-anxiety-disorder/. [Accessed January 2021].
[2] K.-Y. Pan, A. A. Kok, M. Eikelenboom, M. Horsfall, F. Jörg and R. A. Luteijn, “The mental health impact of the COVID-19 pandemic on people with and without depressive, anxiety, or obsessive-compulsive disorders: a longitudinal study of three Dutch case-control cohorts,” The Lancet Psychiatry, pp. 1-9, 2020.
[3] J. B. Byrd and R. D. Brook, “Anxiety in the “Age of Hypertension”,” Current Hypertension Reports , vol. 16, p. 486, 2014.
[4] NHS, “Overview: High blood pressure (hypertension),” NHS, October 2019. [Online]. Available: https://www.nhs.uk/conditions/high-blood-pressure-hypertension/. [Accessed January 2021].
[5] J. J. Burston, A. M. Valdes, S. G. Woodhams, P. I. Mapp, J. Stocks, D. J. Watson, P. R. Gowler, L. Xu, D. R. Sagar, G. Fernandes, N. Frowd, L. Marshall, W. Zhang, M. Doherty, D. A. Walsh and Ch, “The impact of anxiety on chronic musculoskeletal pain and the role of astrocyte activation,” Pain, vol. 160, no. 3, pp. 658-669, 2019.
[6] NHS, “Overview: Arthritis,” NHS, December 2018. [Online]. Available: https://www.nhs.uk/conditions/arthritis/. [Accessed January 2021].
[7] M. Dueñas, B. Ojeda, A. Salazar, J. A. Mico and I. Failde, “A review of chronic pain impact on patients, their social environment and the health care system,” Journal of Pain Research, vol. 9, pp. 457-467, 2016.
[8] C. J. Philips, “Economic burden of chronic pain,” Expert Review of Pharmacoeconomics & Outcomes Research, vol. 6, no. 5, pp. 591-601, 2006

Photo by Anna Shvets from https://www.pexels.com/ 

The post How anxiety may impact our future health appeared first on School of Life Sciences.

During my final year of my degree in neuroscience, I have delved into the function of myelin in a lot of detail¹. Myelin is an important membrane structure of the brain which is made from fats and acts as an insulating and protective layer for neurones². It also increases the speed of transmission of electrical impulses (called action potentials) which are formed by the movement of sodium and potassium ions³. In the brain and spinal cord, cells called oligodendrocytes produce and wrap myelin around axons of the neuron⁴. The membranes provide a thick layer which is impermeable the ions mentioned above¹. This helps action potentials to be carried in one direction and increases the conduction of the action potential as they can undergo saltatory conduction¹. Unmyelinated neurones also exist but these are for slower responses such as digestion². The breakdown of this lipid membrane can cause consequences to neuronal function. This is called demyelination and has been observed in many disorders². When the myelin is lost, the action potentials are slower which could lead to the damage of nerve fibres².

The causes of demyelination are²:

• Inflammation- usually when your body is co-ordinated to attack its own cells (autoimmunity)
• Loss of oxygen to the brain – hypoxic-ischemic demyelination
• Focal compression
• Virus’ (JC virus)

Multiple sclerosis (MS) in particular is a common disorder that causes demyelination. It is a debilitating disorder that affects around 2 1/2 million worldwide⁵. This disorder is termed an autoimmune disorder, when the body’s immune system begins to attack the body⁶. However, it is organ specific; the disorder only affects the brain and spinal cord⁷. One of the consequences of this is that the myelin sheaths can disintegrate. Not only this, but the cells producing myelin (oligodendrocytes and Schwann cells) can also be damaged⁷. In turn this can cause the reduction in the speed of firing of neurons, which can be critical for certain neurones which are required to transmit information at a higher speed⁷. This effect is widespread throughout the nervous system and can impact numerous daily tasks. One of the main effects of this is that this can lower the ability to coordinate movement and therefore reduce the function of the muscles⁷. This can also result in the loss of myelin for axons that are part of vast neural networks necessary in regulating functions such as cognition⁸. Patients with MS can have difficulties with their working memory (short term memory and memory related decision making)⁸.

Indeed, the brain can undergo a process called remyelination⁹. This is a process which is triggered by demyelination. Cells called neural progenitor cells can newly form and move to the area of demyelination and turn into cells that produce oligodendrocytes. However, these cells⁹. However, in patients with MS, these new cells only produce thinner myelin sheaths and are shorter in length⁹. These do not fully cover the neuron’s axon and can still reduction the speed of transmission⁹.

Currently, scientists are attempting to increase the efficiency of remyelination in MS patients are current treatment (immunomodulators) do not aid the improvement of remyelination⁹. Current therapies that have been theorised is cell induced therapy which is to inject stems into areas of the brain with less myelin⁹. This has been conducted in mouse models, but it is easier said than done⁹. Much research is current ongoing to test this theory and if this method is successful, this can definitely change the lives of many MS patients⁹.

References

1. Fields, R. D. Myelin – More than insulation. Science (80-. ). 344, 264–266 (2014).
2. Nave, K.-A. & Werner, H. B. Myelination of the Nervous System: Mechanisms and Functions. Annu. Rev. Cell Dev. Biol. 30, 503–533 (2014).
3. Morell, P. & Quarles, R. H. Characteristic composition of myelin. Basic Neurochem. Princ. Mol. Cell. Med. Neurobiol. 1096 (2012).
4. Bradl, M. & Lassmann, H. Oligodendrocytes: Biology and pathology. Acta Neuropathol. 119, 37–53 (2010).
5. Multiple sclerosis society. MS in the UK. 3 (2016).
6. Martin, R., Lutterotti, A. & Martin, R. and Lutterotti, A. Molecular Basis of Multiple Sclerosis: The Immune System. (2010).
7. Chen, M., Gran, B., Costello, K., Johnson, K. & Martin, R. Multiple Sclerosis. 168–171 (2001). doi:10.1177/135245850100700401
8. Karavasilis, E. et al. Hippocampal structural and functional integrity in multiple sclerosis patients with or without memory impairment: a multimodal neuroimaging study. Brain Imaging Behav. 13, 1049–1059 (2019).
9. Olsen, J. A. & Akirav, E. M. Remyelination in multiple sclerosis: Cellular mechanisms and novel therapeutic approaches. Journal of Neuroscience Research 93, 687–696 (2015).

Photo by Colin Behrens from Pixabay

The post Myelin: An unknown saviour for the brain appeared first on School of Life Sciences.