Neuroscience Insights最新文献

Repetitive head trauma in sports, particularly concussions, has been strongly associated with neurocognitive impairments, including depression, chronic traumatic encephalopathy (CTE), and altered brain function. These injuries can have significant consequences on major cognitive processes, such as learning and memory. This review synthesizes research that examines the effects of sports-related head trauma, particularly in football, on cognitive functioning. Post-mortem analyses of players across all positions have revealed neuropathological evidence of CTE, including a distinct reduction in hippocampal volume. Notably, episodic memory, a component of declarative memory, is frequently compromised in individuals with CTE. Furthermore, deficits in working memory may contribute to decreased performance during play. Early detection of head trauma and implementation of preventive strategies are crucial for mitigating long-term consequences. While impact-reducing techniques have shown some efficacy in decreasing brain injury incidence, proper tackling techniques, such as "heads-up play," also play a vital role in minimizing risk. Further research and increased awareness are needed to ensure athletes are fully informed of the potential cognitive risks associated with participation in high-impact sports.

The postpartum period is marked by radical changes in the maternal brain. Seeking to explore the mechanisms that underlie these changes, this article focuses on the relevant hormonal, inflammatory, and behavioral factors. Longitudinal imaging studies have shed valuable light on both short- and long-term alterations in postpartum brain structure and connectivity, particularly in the regions that play key roles in emotion regulation and stress response. It is plausible that these peripartum changes contribute to the mental health challenges new mothers face, including postpartum depression. Adding to our understanding of postpartum neurobiology, this insight highlights the importance of personalized intervention in the promotion of maternal well-being.

Mitochondrial dysfunction plays a pivotal role in the progression of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Alzheimer's, and Parkinson's disease. Recent discoveries have highlighted the involvement of DNA damage and repair processes, particularly mitochondrial DNA (mtDNA) damage, in these conditions. This commentary reflects on our recent findings, demonstrating the RNA/DNA binding protein fused in sarcoma (FUS)'s crucial role in maintaining mtDNA integrity through interactions with mitochondrial DNA ligase IIIα (mtLig3). Our studies provide direct evidence of increased mtDNA damage in ALS-linked FUS mutant cells, emphasizing the potential of targeting DNA repair pathways to mitigate neurodegeneration. Furthermore, the restoration of mitochondrial function through targeted expression of human DNA ligase 1 (Lig1) in FUS mutant models showcases the therapeutic promise of DNA repair mechanisms in neurodegenerative diseases. These insights offer new molecular understanding and open up future avenues for therapeutic interventions, particularly in FUS-associated ALS and related disorders.

Previous studies have indicated that the infralimbic (IL) and prelimbic (PL) subdivisions of the medial prefrontal cortex (mPFC) serve as critical modulators of fear suppression and expression. Although significant research has been conducted on the extinction of conditioned fear, the mechanisms underlying contextual fear discrimination learning, a form of contingency judgment learning, remain inadequately understood. Our investigation aimed to explore the influence of epigenetic regulation associated with cyclic AMP-response element binding protein (CREB)-dependent long-term memory encoding within the IL and PL on contextual fear discrimination. Our prior and current findings illustrate that epigenetic hypofunction induced by a CREB-Binding Protein (CBP) mutant, which is deficient in histone acetyltransferase activity (CBPΔHAT), within the mPFC leads to compromised contextual fear discrimination while not affecting contextual fear conditioning in these mutants. Unexpectedly, the effect was not noticeable when the hypofunction was constrained to the infralimbic (IL) area; however, the hypofunction of the prelimbic (PL) network led to considerable impairment in fear discrimination. The findings indicate that learning fear discrimination involves differential encoding across the specialized networks of the mPFC. These data suggest that the IL network is not essential for encoding during the acquisition and discrimination of fear or that the PL network may compensate for the IL's inability to encode new information. Furthermore, these results emphasize the importance of histone acetylation in the mPFC as a crucial physiological mechanism for learning contingency judgment.

Background: The objective of this study is to examine magnocellular and parvocellular pathways differentiation based on checkerboard spatial frequency stimulation between normal and visually impaired individuals from athletes with mild traumatic brain injury.

Purpose: Athletes who exhibited photophobia, and blurriness were subjected to 5 spatial frequency stimuli presented to the left and right eye, and both eyes simultaneously to determine the type of receptive field loss deprecation based on sports-related brain trauma.

Methods: Checkerboard stimulation enables the measurement between 2 visual processing pathways and enables the determination of the integrity of visual processing through visual evoked potentials (VEPs).

Conclusion: The principal results reflect P1 responses demonstrated distinct changes in amplitude from mTBI (>5 µV) from normal cohorts concluding higher P1 amplitude of the VEP in mTBI cohorts had increased after injury. Latency in P1 was not as distinct as amplitude changes. Our major conclusion is that most of the mTBI cohort exhibited receptive field loss across all the patients appears to be magnocellular process deprecation due to frequent instances of 8 × 8 and 16 × 16 spatial frequencies input as it relates to amplitude and latency output.

The human brain contains multiple cell types that are spatially organized into functionally distinct regions. The proper development of the brain requires complex gene regulation mechanisms in both neurons and the non-neuronal cell types that support neuronal function. Studies across the last decade have discovered that the 3D nuclear organization of the genome is instrumental in the regulation of gene expression in the diverse cell types of the brain. In this review, we describe the fundamental biochemical mechanisms that regulate the 3D genome, and comprehensively describe in vitro and ex vivo studies on mouse and human brain development that have characterized the roles of the 3D genome in gene regulation. We highlight the significance of the 3D genome in linking distal enhancers to their target promoters, which provides insights on the etiology of psychiatric and neurological disorders, as the genetic variants associated with these disorders are primarily located in noncoding regulatory regions. We also describe the molecular mechanisms that regulate chromatin folding and gene expression in neurons. Furthermore, we describe studies with an evolutionary perspective, which have investigated features that are conserved from mice to human, as well as human gained 3D chromatin features. Although most of the insights on disease and molecular mechanisms have been obtained from bulk 3C based experiments, we also highlight other approaches that have been developed recently, such as single cell 3C approaches, as well as non-3C based approaches. In our future perspectives, we highlight the gaps in our current knowledge and emphasize the need for 3D genome engineering and live cell imaging approaches to elucidate mechanisms and temporal dynamics of chromatin interactions, respectively.

Stroke remains a leading cause of mortality and disability, with ischemic stroke being the most common type. It occurs due to reduced cerebral blood flow, leading to a cascade of events initiated by oxygen and nutrient deprivation, triggering excitotoxicity, oxidative stress, and inflammation and finally culminating in neuronal injury and death. Key molecular players in ischemic stroke include glutamate receptors, acid-sensing ion channels, and purinergic receptors, exacerbating cellular damage through calcium influx, oxidative stress, and mitochondrial dysfunction. Understanding these mechanisms has shaped therapeutic strategies, such as neuroprotective agents and stem cell therapies. Current treatments such as tissue plasminogen activator (tPA) emphasize timely intervention, yet challenges persist in patient-specific variability and accessibility. This review provides an overview of ischemic stroke pathophysiology, emphasizing cellular responses to ischemia and current and future therapeutic approaches including stem cell therapies aimed at mitigating stroke-induced disabilities and improving long-term outcomes.

Increasing evidence documents turnover of the resting-state blood-oxygen-level dependent signal (TBOLD) as a key measure of local cortical brain status. Here we evaluated contemporaneous and lagged associations between TBOLD and cognitive function in 711 participants in the Human Connectome Project on Aging (HCP-A; 316 males and 395 females, age range 36-90 years). We found that TBOLD was negatively associated with Montreal Cognitive Assessment (MoCA) Total scores and with performance on 2 subscales, Delayed Recall and Visuospatial/Executive Function, controlling for sex, age, and handedness. This negative association was largely documented across brain areas and was significantly stronger in the left hemisphere compared to the right. In addition, analyses evaluating forward lagged crosscorrelations between TBOLD and cognitive performance demonstrated that TBOLD predicted decrements in future performance on MoCA Total score, Delayed Recall, and Visuospatial/Executive Function subscales, controlling for sex and handedness. Taken together, we found that increased TBOLD is associated with decreased cognitive performance contemporaneously and in the future. On the hypothesis that increased TBOLD is the outcome of neuroinflammatory processes, these findings provide a mechanism linking neuroinflammation with decreased cognitive performance.

Cerebral amyloid angiopathy (CAA) is a common disorder of the elderly, a prominent comorbidity of Alzheimer's disease, and causes vascular cognitive impairment and dementia. Previously, we generated a novel transgenic rat model (rTg-D) that produces human familial CAA Dutch E22Q mutant amyloid β-protein (Aβ) in brain and develops arteriolar CAA type-2. Here, we show that deposition of fibrillar Aβ promotes arteriolar smooth muscle cell loss and cerebral microhemorrhages that can be detected by magnetic resonance imaging and confirmed by histopathology. Aged rTg-D rats also present with cognitive deficits. Cerebral proteomic analyses revealed 241 proteins that were significantly elevated with an increase of >50% in rTg-D rats presenting with CAA compared to wild-type rats. Fewer proteins were significantly decreased in rTg-D rats. Of note, high temperature requirement peptidase A (HTRA1), a proteinase linked to transforming growth factor beta 1 (TGF-β1) signaling, was elevated and found to accumulate in cerebral vessels harboring amyloid deposits. Pathway analysis indicated elevation of the TGF-β1 pathway and increased TGF-β1 levels were detected in rTg-D rats. In conclusion, the present findings provide new molecular insights into the pathogenesis of CAA and suggest a role for interactions between HTRA1 and TGF-β1 in the disease process.

The SARS-CoV-2 virus is primarily a respiratory virus, but, as it spread worldwide, it became apparent that there are multiple extrapulmonary manifestations. Reports arose of young and otherwise healthy patients presenting to emergency departments with large-vessel occlusions. Because of a rapidly evolving pandemic, conflicting data sometimes arose regarding the impact of the pandemic on strokes. COVID-19 can induce a hypercoagulable and a proinflammatory state through the interactions with the ACE-2 receptor. These mechanisms may lead to the strokes, both ischemic and hemorrhagic, that are seen in this infection. Strokes, in conjunction with COVID-19 infection, tended to be more disabling and portended a higher mortality. Treatment of these strokes was challenging, as emergency departments were strained with the high burden of COVID-19 admissions. Finally, vaccines against COVID-19 were widely administered, and their potential to cause stroke as an adverse event are discussed. This article will provide an in depth review of the recent updates about the incidence, epidemiology, pathophysiology, clinical presentation and treatment of strokes that are associated with COVID-19.