Best and Worst of Neuroscience and Neurology – March 2016by Viatcheslav Wlassoff, PhD | April 16, 2016
In this article I present a selection of publications that came out in March. There were many interesting developments, both in fundamental neuroscience and neurology, and in the practical aspects of dealing with brain-related diseases and disorders.
On March 20th, the scientific community marked the birthday of Erwin Neher, who received the 1991 Nobel Price in Physiology and Medicine for discovering the functions of single ion channels in cells. Together with Bert Sakmann, Neher developed the patch clamp technique that enabled the recording of the current of single ion channel molecule for the first time. The work contributed substantially to the fundamental understanding of nerve activity.
This idea has a potential to revolutionize the treatment of Alzheimer’s disease. And the proof of concept was just published this month.
In the animal experiments, researchers implanted a capsule containing specifically modified cells under the skin of mice. The cells produce antibodies against amyloid-beta, a protein that is known to over-accummulate in the brain of patients with Alzheimer’s disease and eventually causes neurodegeneration. The capsule gradually releases antibodies and thus successfully prevents the formation of amyloid-beta plagues. Implementation of a similar device suitable for human treatment may pave the way to significantly reducing the burden of Alzheimer’s disease and similar neurodegenerative conditions.
Pain relief due to meditation is opioid-free
Pain is a natural reaction to the body harm that warn us of potential or present damage. What eventually stops us feeling the pain is the internal production of natural opioids. Cognitive approaches to reducing pain, such as distraction, acupuncture, hypnosis and even placebo, all work through this opioid-based mechanism.
When researchers attempted to find out if the same is true for meditation, the result came as a surprise. In experiments where scientists blocked the opioid receptors in the body using a drug targeting them, meditation was still capable of providing the pain relief. The findings point to the existence of yet another molecular mechanism of pain relief, which needs to be further investigated. Such studies might help in developing new painkillers that are especially needed for people with chronic pain who developed resistance to opiate-based drugs.
Exercise significantly slows down brain aging
The benefits of exercise are well known and widely publicized. New research data have convincingly demonstrated yet another advantage of being physically active: exercise slows down the aging of brain. The long-term North Manhattan study data show that physically active elderly individuals perform much better in the cognitive tests compared to their sedentary counterpart. In fact, the difference in tests results equals to about 10 years difference in the brain age!
Structure of Parkinson’s protein finally characterized
One of the reasons Parkinson’s disease is still poorly manageable is the lack of well-studied suitable molecular targets. The protein alpha-synuclein is the major culprit in the development and progression of this condition: it forms insoluble fibrils disrupting the brain cells activity. Unfortunately, due to the complexity of alpha-synuclein fibrils, their molecular structure has been poorly investigated.
This gap in knowledge was filled with the report published this month that outlines high-resolution molecular details of alpha-synuclein deposits. The findings will help in identification of suitable pharmaceutical targets and, eventually, in developing the drugs directed at them.
Bacteria from GI tract can reduce severity of stroke
We know that the brain and the gastrointestinal (GI) tract “talk” – this is particularly obvious when it comes to the regulation of appetite and body weight. But it appears that the relationship might be much more complex than previously thought. Certain bacteria residing in the GI tract may modify our immune system in such a way that it can decrease the severity of stroke.
In the recently published study, researchers demonstrated that the severity of induced ischemic stroke in mice treated with antibiotics is reduced by 60%. Antibiotics can change the balance of different bacterial species in GI tract. The bacteria, in turn, can modify the cells of the immune system that assemble on the meninges, the outer covering of brain. These cells modify and direct the response to stroke. The discovery open the way of reducing the severity of potential stroke in vulnerable patients through pharmaceutical or dietary interventions.
Western diet might facilitate development of Alzheimer’s disease
The classical Western diet–rich on fat, sugars and animal products–is known to be unhealthy and linked to obesity and associated chronic conditions, such as cardiovascular problems, strokes and some cancers.
New findings suggest that this diet can also increase the chances of developing Alzheimer’s disease at older age. At least this is what was demonstrated in the experiments on laboratory animals. Mice that were kept on a “Western diet” chow for ten months demonstrated dramatic increase in the activity of microglia and monocytes in the brain. Both types of cells function as components of immune system in the brain, and their increased activity is known to elevate susceptibility to Alzheimer’s disease.
Higher BMI leads to poorer memory
The findings above correlate well with the recent report from the University of Cambridge showing that excess body weight correlates with poorer memory. Higher BMI values were shown to correlate with poor performance in the tests on forming and retrieving episodic memories. It appears that this effect is linked to the previously found structural and functional changes in the brain of obese people. These changes were identified in the hippocampus, a key area of the brain responsible for memory and learning, and the frontal lobe, which is involved in problem solving and decision making.
Common contraceptive increases the risk of seizures
A commonly used contraceptive drug, ethinyl estradiol, was shown to increase the frequency of seizures in women suffering from epilepsy. Women with epilepsy taking this drug experience seizures 4.5 times more often. In addition, the seizures last longer, exposing the brain to potential permanent damage.
Dopamine receptor agonists do not help in schizophrenia
At present time, we have no efficient treatments for the negative and cognitive effects associated with schizophrenia. Previous findings provided hope that treatment with low-dose dopamine-1 receptor (D1R) agonists may address this problem. In the study published this month, researchers used functional MRI to evaluate the effects of D1R agonist on the activity of brain performing a working memory task. Disappointingly, no treatment effect was observed.
Prolonged stress is damaging for memory
Extended periods of stress were shown to damage memory. In the study published this month, researchers induced sustained stress in mice by repeatedly exposing them to an intruding aggressive alpha-male. This is a kind of satiation that can be often encountered in human society when people are exposed to bullying by peers or an abusive boss at work. Chronically stressed mice demonstrated worsened performance in cognitive tests: for example, they weren’t able to navigate a maze previously known to them fast enough. Importantly, the erosion of memory was linked to the increased level of inflammation in brain that was caused primarily by increased level of macrophages.
The findings can potentially redirect the research on treating the chronic stress towards its immune components.
Benakis, C., Brea, D., Caballero, S., Faraco, G., Moore, J., Murphy, M., Sita, G., Racchumi, G., Ling, L., Pamer, E., Iadecola, C., & Anrather, J. (2016). Commensal microbiota affects ischemic stroke outcome by regulating intestinal ?? T cells Nature Medicine DOI: 10.1038/nm.4068
Cheke, L., Simons, J., & Clayton, N. (2016). Higher body mass index is associated with episodic memory deficits in young adults The Quarterly Journal of Experimental Psychology, 1-12 DOI: 10.1080/17470218.2015.1099163
Girgis, R., Van Snellenberg, J., Glass, A., Kegeles, L., Thompson, J., Wall, M., Cho, R., Carter, C., Slifstein, M., Abi-Dargham, A., & Lieberman, J. (2016). A proof-of-concept, randomized controlled trial of DAR-0100A, a dopamine-1 receptor agonist, for cognitive enhancement in schizophrenia Journal of Psychopharmacology DOI: 10.1177/0269881116636120
Graham, L., Harder, J., Soto, I., de Vries, W., John, S., & Howell, G. (2016). Chronic consumption of a western diet induces robust glial activation in aging mice and in a mouse model of Alzheimer’s disease Scientific Reports, 6 DOI: 10.1038/srep21568
Lathuilière, A., Laversenne, V., Astolfo, A., Kopetzki, E., Jacobsen, H., Stampanoni, M., Bohrmann, B., Schneider, B., & Aebischer, P. (2016). A subcutaneous cellular implant for passive immunization against amyloid-? reduces brain amyloid and tau pathologies Brain DOI: 10.1093/brain/aww036
McKim, D., Niraula, A., Tarr, A., Wohleb, E., Sheridan, J., & Godbout, J. (2016). Neuroinflammatory Dynamics Underlie Memory Impairments after Repeated Social Defeat Journal of Neuroscience, 36 (9), 2590-2604 DOI: 10.1523/JNEUROSCI.2394-15.2016
Tuttle, M., Comellas, G., Nieuwkoop, A., Covell, D., Berthold, D., Kloepper, K., Courtney, J., Kim, J., Barclay, A., Kendall, A., Wan, W., Stubbs, G., Schwieters, C., Lee, V., George, J., & Rienstra, C. (2016). Solid-state NMR structure of a pathogenic fibril of full-length human ?-synuclein Nature Structural & Molecular Biology DOI: 10.1038/nsmb.3194
Willey, J., Gardener, H., Caunca, M., Moon, Y., Dong, C., Cheung, Y., Sacco, R., Elkind, M., & Wright, C. (2016). Leisure-time physical activity associates with cognitive decline: The Northern Manhattan Study Neurology DOI: 10.1212/WNL.0000000000002582
Younus, I., & Reddy, D. (2016). Seizure facilitating activity of the oral contraceptive ethinyl estradiol Epilepsy Research, 121, 29-32 DOI: 10.1016/j.eplepsyres.2016.01.007
Zeidan, F., Emerson, N., Farris, S., Ray, J., Jung, Y., McHaffie, J., & Coghill, R. (2015). Mindfulness Meditation-Based Pain Relief Employs Different Neural Mechanisms Than Placebo and Sham Mindfulness Meditation-Induced Analgesia Journal of Neuroscience, 35 (46), 15307-15325 DOI: 10.1523/JNEUROSCI.2542-15.2015
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