Neuroscience Insights最新文献

During nervous system development, axons must navigate to specific target areas. In Caenorhabditis elegans, the cadherin CDH-4 is required for ventral nerve cord axonal navigation, and dorsal nerve cord fasciculation. How CDH-4 mediates axon navigation and fasciculation is currently unknown. To identify genes acting together with cdh-4, we isolated mutants suppressing the axon guidance defects of cdh-4 mutants. These suppressors showed partial suppression of axonal defects in the dorsal and ventral nerve cords seen in cdh-4 mutants. We identified one suppressor gene, prp-6, which encodes a component of the spliceosome. Complete loss-of-function alleles of prp-6 are lethal, suggesting that the mutation isolated in our suppressor screen is a partial loss-of-function allele. A previous study found that RNAi-induced suppression of prp-6 leads to changes in the expression of several 100 genes including the cadherin cdh-5. We found that overexpression of cdh-5 mimics the suppression seen in prp-6 mutants, suggesting that CDH-5 can partially compensate for the loss of CDH-4.

In the wild, animals face different challenges including multiple events of food scarcity. How they overcome these conditions is essential for survival. Thus, adaptation mechanisms evolved to allow the development and survival of an organism during nutrient restriction periods. Given the high energy demand of the nervous system, the molecular mechanisms of adaptation to malnutrition are of great relevance to fuel the brain. The blood-brain barrier (BBB) is the interface between the central nervous system (CNS) and the circulatory system. The BBB mediates the transport of macromolecules in and out of the CNS, and therefore, it can buffer changes in nutrient availability. In this review, we collect the current evidence using the fruit fly, Drosophila melanogaster, as a model of the role of the BBB in the adaptation to starvation. We discuss the role of the Drosophila BBB during nutrient deprivation as a potential sensor for circulating nutrients, and transient nutrient storage as a regulator of the CNS neurogenic niche.

Separated face- and body-responsive brain networks have been identified that show strong responses when observers view faces and bodies. It has been proposed that face and body processing may be initially separated in the lateral occipitotemporal cortex and then combined into a whole person representation in the anterior temporal cortex, or elsewhere in the brain. However, in contrast to this proposal, our recent study identified a common coding of face and body orientation (ie, facing direction) in the lateral occipitotemporal cortex, demonstrating an integration of face and body information at an early stage of face and body processing. These results, in combination with findings that show integration of face and body identity in the lateral occipitotemporal, parahippocampal and superior parietal cortex, and face and body emotional expression in the posterior superior temporal sulcus and medial prefrontal cortex, suggest that face and body integration may be more distributed than previously considered. I propose a new model of face and body integration, where areas at the intersection of face- and body-responsive regions play a role in integrating specific properties of faces and bodies, and distributed regions across the brain contribute to high-level, abstract integration of shared face and body properties.

Human functional brain imaging research over the last 2 decades has shown that data from resting-state brain activity can help predict various psychological and pathological variables and brain function during tasks. However, most variables have been attributed to the individual brain. Recently, several studies have aimed to understand interpersonal relationships based on inter-individual similarity or dissimilarity of functional connectome. In this commentary, we introduce the studies that have opened up a new era of interpersonal research using human brain imaging.

Dementia, Parkinson's disease, multiple sclerosis, and motor neuron diseases cause significant disability and mortality worldwide. Although the etiology of these diseases is unknown, highly correlated disease prevalences would indicate the involvement of common etiologic factors. Here we used published epidemiological data in 195 countries worldwide to investigate the possible intercorrelations among the prevalences of these diseases. All analyses were carried out using nonparametric statistics on rank-transformed data to assure the robustness of the results. We found that all 6 pairwise correlations among the prevalences of the 4 diseases were very high (>.9, P < .001). A factor analysis (FA) yielded only a single component which comprised all 4 disease prevalences and explained 96.3% of the variance. These findings indicate common etiologic factor(s). Next, we quantified the contribution of 3 country-specific factors (population size, life expectancy, latitude) to the common grouping of prevalences by estimating the reduction in total FA variance explained when the effect of these factors was eliminated by using the prevalence residuals from a linear regression where theses factor were covariates. FA of these residuals yielded again only a single component comprising all 4 diseases which explained 71.5% of the variance, indicating that the combined contribution of population size, life expectancy and latitude accounted for 96.3% - 71.5% = 24.8% of the FA variance explained. The fact that the 3 country-specific factors above accounted for only 24.8% of the FA variance explained by the original (ranked) disease prevalences, in the presence still of a single grouping factor, strongly indicates the operation of other unknown factors jointly contributing to the pathogenesis of the 4 diseases. We discuss various possible factors involved, with an emphasis on biologic pathogens (viruses, bacteria) which have been implicated in the pathogenesis of these diseases in previous studies.

The history of cerebral aneurysm treatment has a rich and storied past with multiple notable luminaries contributing insights. The modern era has transitioned from primarily clip ligation to increasing use of endovascular therapy. Even more recently, the use of intrasaccular flow diverters has been introduced for the treatment of wide necked aneurysms. The field is continuing to transform, and bioactive coils and stents have resurfaced as promising adjuvants to promote aneurysm healing. Advanced imaging modalities are being developed that could further advance the endovascular arsenal and allow for porous memory polymer devices to enter the field. This focused review highlights notable historic contributions and advances to the point of futuristic technology that is actively being developed.

Obsessive-compulsive disorder (OCD) is a chronic and debilitating mental disorder that affects patients throughout their lives, leading to a diminished quality of life for patients and families, reduced productivity, and higher health care costs. It is of clinical and theoretical importance to investigate a more efficacious therapeutic approach for OCD and the neurophysiological mechanism underlying the efficacy of treatment, potentially associated with the etiology of OCD. Recently, a novel psychotherapy designated cognitive-coping therapy (CCT) has been reported to have a large effect size in OCD treatment. CCT hypothesizes that fear of negative events plays a crucial role in OCD. The study entitled "Decreased left amygdala functional connectivity by cognitive-coping therapy in obsessive-compulsive disorder" attempted to investigate the potential neurophysiological mechanism underlying the efficacy of CCT for OCD. The study provides crystal evidence showing that 4-week pharmacotherapy plus CCT decreases the left amygdala seed-based functional connectivity (LA-FC) with the right anterior cingulate gyrus and the left paracentral lobule/the left superior parietal/left inferior parietal, and 4-week CCT decreases the LA-FC with the left middle occipital gyrus/the left superior parietal. The alteration of the LA-FC with the right anterior cingulate gyrus positively correlates to the reduction of the Yale-Brown obsessive-compulsive scale (Y-BOCS) score. Therefore, it provides new insights into understanding the neurophysiology and neuropsychology behind the onset and treatment of OCD.

Purpose: To investigate the effectiveness of perturbation-based training (PBT) on balance and balance confidence in patients with stroke.

Methods: Systematic searching was performed from inception to November 2021. The inclusion criteria were RCTs assessed the effectiveness of PBT in patients with stroke. Data regarding participants, intervention parameters, outcome measures, follow-up, and main results were extracted. The outcomes were balance and balance confidence. Methodological quality and quality of evidence were assessed using the Physiotherapy Evidence Database (PEDro) scale and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system; respectively.

Data analysis: A total of 7 articles )271 patients) were included. A meta-analysis using a random-effect model was performed on 6 studies. Standardized mean difference (SMD) with a 95% confidence interval was calculated for balance and balance confidence.

Results: PEDro scale revealed 5 good-quality and 2 fair-quality studies. The currently available evidence showed significant effect of PBT in improving balance (SMD 0.60 [95% CI 0.15-1.06]; P = .01; very low-quality evidence) and non-significant in improving balance confidence (SMD 0.11 [95% CI -0.24 to 0.45]; P = .55; low-quality evidence).

Conclusion: PBT may improve balance in patients with stroke, however its effect on balance confidence was limited. The quality of the evidence was low or very low with little confidence in the effect estimate, which suggests further high-quality trials are required.

Registration: PROSPERO registration number (CRD42021291474).

Several foreign antigens such as those derived from viruses and bacteria have been linked to long-term deleterious effects on the brain and other organs; yet, health outcomes subsequent to foreign antigen exposure vary depending in large part on the host's immune system, in general, and on human leukocyte antigen (HLA) composition, in particular. Here we first provide a brief description of 3 conditions characterized by persistent long-term symptoms, namely long-COVID-19, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and Gulf War Illness (GWI), followed by a brief overview of the role of HLA in the immune response to foreign antigens. We then discuss our Persistent Antigen (PA) hypothesis and highlight associations between antigen persistence due to HLA-antigen incongruence and chronic health conditions in general and the 3 "long" diseases above in particular. This review is not intended to cover the breadth and depth of symptomatology of those diseases but is specifically focused on the hypothesis that the presence of persistent antigens underlies their pathogenesis.

Vascular dysfunction plays a critical role in the development of Alzheimer's disease. Cerebral blood flow reductions of 10% to 25% present early in disease pathogenesis. Vascular Endothelial Growth Factor-A (VEGF-A) drives angiogenesis, which typically addresses blood flow reductions and global hypoxia. However, recent evidence suggests aberrant VEGF-A signaling in Alzheimer's disease may undermine its physiological angiogenic function. Instead of improving cerebral blood flow, VEGF-A contributes to brain capillary stalls and blood flow reductions, likely accelerating cognitive decline. In this commentary, we explore the evidence for pathological VEGF signaling in Alzheimer's disease, and discuss its implications for disease therapy.