Neuroscience Insights最新文献

Neural progenitor cell (NPC) transplantation is a promising potential therapy for replacing spinal cord neurons and glial cells following spinal cord injury (SCI). Despite the rapid advancement of NPC transplantation to SCI clinical trials, we still lack understanding of fundamental biology underlying how NPC grafts interact with the injured host nervous system. Our recent study demonstrated a potent effect of biological sex mismatch between donor and host on graft immune rejection. Here we discuss the implications of this study in the context of clinical trials for SCI, and important topics for future research in SCI cell transplantation.

Hypertension is considered one of the most critical risk factors for COVID-19. Evidence suggests that SARS-CoV-2 infection produces intense effects on the cardiovascular system by weakening the wall of large vessels via vasa-vasorum. In this commentary, we propose that SARS-CoV-2 invades carotid and aortic baroreceptors, leading to infection of the nucleus tractus solitari (NTS) and paraventricular hypothalamic nucleus (PVN), and such dysregulation of NTS and PVN following infection causes blood pressure alteration at the central level. We additionally explored the hypothesis that SARS-CoV-2 favors the internalization of membrane ACE2 receptors generating an imbalance of the renin-angiotensin-aldosterone system (RAAS), increasing the activity of angiotensin II (ANG-II), disintegrin, and metalloproteinase 17 domain (ADAM17/TACE), eventually modulating the integration of afferents reaching the NTS from baroreceptors and promoting increased blood pressure. These mechanisms are related to the increased sympathetic activity, which leads to transient or permanent hypertension associated with SARS-CoV-2 invasion, contributing to the high number of deaths by cardiovascular implications.

Several factors have been implicated in schizophrenia (SZ), including human herpes viruses (HHV) and the adaptive immunity Human Leukocyte Antigen (HLA) genes. Here we investigated these issues in 2 complementary ways. In one analysis, we evaluated SZ-HLA and HHV-HLA associations at the level of a single allele by computing (a) a SZ-HLA protection/susceptibility (P/S) score based on the covariance between SZ and 127 HLA allele prevalences in 14 European countries, (b) estimating in silico HHV-HLA best binding affinities for the 9 HHV strains, and (c) evaluating the dependence of P/S score on HHV-HLA binding affinities. These analyses yielded (a) a set of 127 SZ-HLA P/S scores, varying by >200× (maximum/minimum), which could not be accounted for by chance, (b) a set of 127 alleles × 9 HHV best-estimated affinities, varying by >600×, and (c) a set of correlations between SZ-HLA P/S scores and HHV-HLA binding which indicated a prominent role of HHV1. In a subsequent analysis, we extended these findings to the individual person by taking into account the fact that every individual carries 12 HLA alleles and computed (a) the average SZ-HLA P/S scores of 12 randomly chosen alleles (2 per gene), an indicator of HLA-based SZ P/S for an individual, and (b) the average of the corresponding HHV estimated affinities for those alleles, an indicator of overall effectiveness of HHV-HLA binding. We found (a) that HLA protection for SZ was significantly more prominent than susceptibility, and (b) that protective SZ-HLA scores were associated with higher HHV-HLA binding affinities, indicating that HLA binding and subsequent elimination of several HHV strains may confer protection against schizophrenia.

Neuropsychological symptoms associated with post-COVID-19 conditions may prevent patients from resuming normal activities at home or work. We report a retrospective, cross-sectional evaluation of neuropsychological and cardiopulmonary outcomes in 2 groups of patients: outpatients with mild enough infection to be spared from hospitalization and those who required inpatient admission. We hypothesized a dose-response model of post-COVID symptom severity in which persistent consequences would be more severe in those who experienced worse acute infections. In a dedicated COVID clinic, 321 patients were seen (33% outpatient, 67% inpatient). Outpatients skewed female, White, non-Hispanic, and younger. Outpatients had worse insomnia (measured with insomnia severity index) and were less able to resume their usual activities (EQ-5D-5L usual activities scale), despite inpatients experiencing worse cognition (Montreal Cognitive Assessment), having greater obesity (body mass index), decreased exercise tolerance (6-minute-walk distance), and more exertional oxygen desaturation. In both groups, insomnia worsened while cognition improved significantly with time from infection to testing while controlling for patient age; other variables did not. In logistic regression, female sex, higher MoCA score, EQ-5D-5L "usual activities" subscore, less oxygen desaturation with exertion, and longer time from infection remained as significant associations with outpatient status. Our study demonstrated that the functional sequelae of post-COVID-19 conditions in patients with mild acute disease have the potential to be as severe as that in patients who have recovered from severe illness.

The urgent need for medical treatments of alcohol use disorders has motivated the search for novel molecular targets of alcohol response. Most studies exploit the strengths of lab animals without considering how these and other species may have adapted to respond to alcohol in an ecological context. Here, we provide an evolutionary perspective on the molecular and genetic underpinnings of alcohol consumption by reviewing evidence that alcohol metabolic enzymes have undergone adaptive evolution at 2 evolutionary junctures: first, to enable alcohol consumption accompanying the advent of a frugivorous diet in a primate ancestor, and second, to decrease the likelihood of excessive alcohol consumption concurrent with the spread of agriculture and fermentation in East Asia. By similarly considering how diverse vertebrate and invertebrate species have undergone natural selection for alcohol responses, novel conserved molecular targets of alcohol are likely be discovered that may represent promising therapeutic targets.

Recent evidence documented a protective effect of Class II human leukocyte antigen (HLA) DRB1*13 on brain health across the lifespan including evidence of reduced neural network variability relative to non-carriers. Here, in an extension of those findings, we evaluated the influence of a large number of Class I and Class II HLA alleles on aging-related changes in neural network variability. Cognitively healthy women (N = 178) ranging in age from 28 to 99 years old underwent a magnetoencephalography scan from which neural network variability was calculated and provided a blood sample from which HLA and apolipoprotein E (ApoE) genotype were determined. The primary analyses assessed the dependence of network variability on age in carriers of a specific HLA allele compared to non-carriers. Effects were considered protective if there was a significant increase of network variability with age in the absence of a given HLA allele but not in its presence, and were considered to confer susceptibility if the converse was documented; HLA alleles that did not influence the dependence of network variability on age in their presence or absence were considered neutral. Of 50 alleles investigated, 22 were found to be protective, 7 were found to confer susceptibility, and 21 were neutral. The frequencies of those 50 alleles were not associated significantly with ApoE genotype. The findings, which document the influence of HLA on age-related brain changes and highlight the role of HLA in healthy brain function, are discussed in terms of the role of HLA in the human immune response to foreign antigens.

There is currently an epidemic of sedentary behavior throughout the world, leading to negative impacts on physical health and contributing to both mortality and burden of disease. The consequences of this also impact the brain, where increased levels of cognitive decline are observed in individuals who are more sedentary. This review explores the physiological and molecular responses to our sedentary propensity, its contribution to several medical conditions and cognitive deficits, and the benefits of moderate levels of physical activity and exercise. Also presented is the recommended level of activity for overall physical health improvement.

In December 2019, a new severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) was first reported in China. It would quickly spread and emerge as a COVID-19 pandemic. The illness caused by SARS CoV-2 would fall on a clinical spectrum ranging from asymptomatic, mild to severe respiratory symptoms, ARDS, and death. This led to significant morbidity and mortality further impacting at-risk populations with severe complications. Thus, a concerted worldwide effort to meet the challenges of diagnosing, treating, and preventing COVID-19 led to rapid advances in medicine. Some mitigating methods of masking, social distancing, and frequent handwashing, helped to slow the spread of SARS-CoV-2. Effective therapeutics consisting of antivirals and monoclonal antibodies, plus their use for prophylaxis, contributed to the management of COVID-19. The vaccines from various platforms (mRNA, viral vectors, protein base, and inactivated) contributed to decreased incidence, severity, and overall decreased hospitalizations and mortality. This article aims to review the novel mRNA vaccines (Moderna + Pfizer/BioNTech), viral vector (Janssen& Johnson), and protein base (Novavax), their side effects, and their use as boosters.

The coronavirus disease 2019 (COVID-19) pandemic has had an enormous impact on practically every aspect of daily life, and those with neuromuscular disorders have certainly not been spared. The effects of COVID-19 infection are far-reaching, going well beyond respiratory symptoms alone. From simple myalgias to debilitating critical illness neuromyopathies, we continue to learn and catalog the diverse pathologies presented by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as it relates to the neuromuscular system. Complications have been documented both as a direct result of primary infection but also in those with pre-existing neuromuscular disorders from myasthenia gravis to devastating critical illness neuromyopathies. In this review, we will discuss the relationship between COVID-19 infection and critical illness neuromyopathy, peripheral nerve palsies, myalgias, positional compressive neuropathy, myasthenia gravis, and Guillain-Barré syndrome.