Neuroscience Insights最新文献

Initially, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease-2019 (COVID-19), was predominantly considered to primarily affect the respiratory system. However, later studies revealed that it also affects brain function through its ability to bind to the angiotensin-converting enzyme type 2 (ACE2) receptors expressed on neural cells. Our study involved a comprehensive review of literature aiming to investigate the relationship between COVID-19 and the development of depression. Our analysis shows a connection between these 2 conditions, as a consequence of the inflammatory response in the nervous system to the COVID-19 virus and the psychophysiological effects of the pandemic. In COVID-19 patients, depression can arise either due to the direct viral infection of the brain or as a result of an indirect immune response triggering neuroinflammation after a cytokine storm. The resulting depression can be treated with non-pharmacological therapies such as psychotherapy, antidepressant medications, or a combination of these treatments depending on the severity of the symptoms.

The SARS-CoV-2 virus caused an unprecedented pandemic around the globe, infecting 36.5 million people and causing the death of over 1 million in the United States of America alone. COVID-19 patients demonstrated respiratory symptoms, cardiovascular complications, and neurologic symptoms, which in most severe cases included encephalopathy and encephalitis. Hypoxia and the uncontrolled proliferation of cytokines are commonly recognized to cause encephalopathy, while the retrograde trans-synaptic spread of the virus is thought to cause encephalitis in SARS-CoV-2-induced pathogenesis. Although recent research revealed some mechanisms explaining the development of neurologic symptoms, it still remains unclear whether interactions between these mechanisms exist. This review focuses on the discussion and analysis of previously reported hypotheses of SARS-CoV-2-induced encephalopathy and encephalitis and looks into possible overlaps between the pathogenesis of both neurological outcomes of the disease. Promising therapeutic approaches to prevent and treat SARS-CoV-2-induced neurological complications are also covered. More studies are needed to further investigate the dominant mechanism of pathogenesis for developing more effective preventative measures in COVID-19 cases with the neurologic presentation.

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.

Several studies have shown that amyloid-β (Aβ) deposition below the clinically relevant cut-off levels is associated with subtle changes in cognitive function and increases the risk of developing future Alzheimer's disease (AD). Although functional MRI is sensitive to early alterations occurring during AD, sub-threshold changes in Aβ levels have not been linked to functional connectivity measures. This study aimed to apply directed functional connectivity to identify early changes in network function in cognitively unimpaired participants who, at baseline, exhibit Aβ accumulation below the clinically relevant threshold. To this end, we analyzed baseline functional MRI data from 113 cognitively unimpaired participants of the Alzheimer's Disease Neuroimaging Initiative cohort who underwent at least one ¹⁸F-florbetapir-PET after the baseline scan. Using the longitudinal PET data, we classified these participants as Aβ negative (Aβ-) non-accumulators (n = 46) and Aβ- accumulators (n = 31). We also included 36 individuals who were amyloid-positive (Aβ+) at baseline and continued to accumulate Aβ (Aβ+ accumulators). For each participant, we calculated whole-brain directed functional connectivity networks using our own anti-symmetric correlation method and evaluated their global and nodal properties using measures of network segregation (clustering coefficient) and integration (global efficiency). When compared to Aβ- non-accumulators, the Aβ- accumulators showed lower global clustering coefficient. Moreover, the Aβ+ accumulator group exhibited reduced global efficiency and clustering coefficient, which at the nodal level mainly affected the superior frontal gyrus, anterior cingulate cortex, and caudate nucleus. In Aβ- accumulators, global measures were associated with lower baseline regional PET uptake values, as well as higher scores on the Modified Preclinical Alzheimer Cognitive Composite. Our findings indicate that directed connectivity network properties are sensitive to subtle changes occurring in individuals who have not yet reached the threshold for Aβ positivity, which makes them a potentially viable marker to detect negative downstream effects of very early Aβ pathology.

The term mild cognitive impairment (MCI) defines an intermediate state between normal aging and dementia. Vascular cognitive impairment refers to a decline in cognitive function that is caused by or associated with vascular disease and comprises all the spectrum of cognitive impairments, from MCI of vascular origin to vascular dementia. One of the available treatments for cognitive impairment is cytidine diphosphate-choline (CDP-Choline), or citicoline. The objective of the present manuscript is to provide complete evidence about the efficacy of citicoline for MCI, especially of vascular origin, but also due to other neurodegenerative disorders. Citicoline is a pharmaceutical product constituted by the combination of 2 natural molecules (cytidine and choline) and is marketed as a food supplement. It has been proposed to provide neuroprotective effects through diverse mechanisms of action. Taking into account the available literature, citicoline has shown a consistent improvement in cognitive function in patients with MCI, especially of vascular origin. Moreover, it provides beneficial effects on vascular, Alzheimer, and mixed dementias, stroke sequelae, intracerebral hemorrhages, traumatic brain injuries, and neurodegenerative diseases. Long-term treatment with citicoline has also been demonstrated to be well-tolerated and has not been associated with severe adverse events. Citicoline is a safe, well-tolerated, and promising agent with evidenced neuroprotective properties.

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.