Neuroscience Insights最新文献

{"title":"A Commentary on Mitochondrial Dysfunction and Compromised DNA Repair in Neurodegeneration: The Emerging Role of FUS in ALS.","authors":"Manohar Kodavati, Muralidhar L Hegde","doi":"10.1177/26331055241305151","DOIUrl":"10.1177/26331055241305151","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":"19 ","pages":"26331055241305151"},"PeriodicalIF":2.9,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11645713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142830124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Neuronal Hypofunction of Subdivisions of the Prefrontal Cortex Shows Differential Effects on Contingency Judgment Learning to Gauge Fear Responses.","authors":"Tyler W Bailey, John H Speigel, Johannes Mayer, Edward Korzus","doi":"10.1177/26331055241305378","DOIUrl":"10.1177/26331055241305378","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":"19 ","pages":"26331055241305378"},"PeriodicalIF":2.9,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Visual Evoked Potential Effects on Magnocellular and Parvocellular Pathways from Athletes After Mild Traumatic Brain Injuries.","authors":"Mark H Myers, Nidhish Kalyanakumar, Paul Harris","doi":"10.1177/26331055241303165","DOIUrl":"10.1177/26331055241303165","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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).</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":"19 ","pages":"26331055241303165"},"PeriodicalIF":2.9,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11603483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The 3D Genome in Brain Development: An Exploration of Molecular Mechanisms and Experimental Methods.","authors":"Samir Rahman, Panos Roussos","doi":"10.1177/26331055241293455","DOIUrl":"10.1177/26331055241293455","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":"19 ","pages":"26331055241293455"},"PeriodicalIF":2.9,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ischemic Stroke: Pathophysiology and Evolving Treatment Approaches.","authors":"Dhriti Majumder","doi":"10.1177/26331055241292600","DOIUrl":"https://doi.org/10.1177/26331055241292600","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":"19 ","pages":"26331055241292600"},"PeriodicalIF":2.9,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11497522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142509718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased Resting-State BOLD Turnover (TBOLD) is Associated With Decreased Cognitive Performance During Aging.","authors":"Lisa M James, Peka Christova, Apostolos P Georgopoulos","doi":"10.1177/26331055241292592","DOIUrl":"https://doi.org/10.1177/26331055241292592","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":"19 ","pages":"26331055241292592"},"PeriodicalIF":2.9,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11494529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142509717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebral Proteomic Changes in the rTg-D Rat Model of Cerebral Amyloid Angiopathy Type-2 With Cortical Microhemorrhages and Cognitive Impairments.","authors":"Joseph M Schrader, Mark Majchrzak, Feng Xu, Hedok Lee, Kevin Agostinucci, Judianne Davis, Helene Benveniste, William E Van Nostrand","doi":"10.1177/26331055241288172","DOIUrl":"10.1177/26331055241288172","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":"19 ","pages":"26331055241288172"},"PeriodicalIF":2.9,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11462563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Updates on COVID-19 Associated Strokes.","authors":"Colton Betts, Zane Ahlfinger, Mercy C Udeh, Batool F Kirmani","doi":"10.1177/26331055241287730","DOIUrl":"10.1177/26331055241287730","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":"19 ","pages":"26331055241287730"},"PeriodicalIF":2.9,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroimaging and the Investigation of Drug-Drug Interactions Involving Psychedelics.","authors":"Matthew B Wall, Rebecca Harding, Natalie Ertl, Tommaso Barba, Rayyan Zafar, Mark Sweeney, David J Nutt, Eugenii A Rabiner, David Erritzoe","doi":"10.1177/26331055241286518","DOIUrl":"10.1177/26331055241286518","url":null,"abstract":"<p><p>Psychedelic therapies are an emerging class of treatments in psychiatry with great potential, however relatively little is known about their interactions with other commonly used psychiatric medications. As psychedelic therapies become more widespread and move closer to the clinic, they likely will need to be integrated into existing treatment models which may include one or more traditional pharmacological therapies, meaning an awareness of potential drug-drug interactions will become vital. This commentary outlines some of the issues surrounding the study of drug-drug interactions of this type, provides a summary of some of the relevant key results to date, and charts a way forward which relies crucially on multimodal neuroimaging investigations. Studies in humans which combine Positron Emission Tomography (PET) and functional Magnetic Resonance Imaging (fMRI), plus ancillary measures, are likely to provide the most comprehensive assessment of drug-drug interactions involving psychedelics and the relevant effects at multiple levels of the drug response (molecular, functional, and clinical).</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":"19 ","pages":"26331055241286518"},"PeriodicalIF":2.9,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11462571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GABA, Aging and Exercise: Functional and Intervention Considerations.","authors":"Tom S Novak, Keith M McGregor, Lisa C Krishnamurthy, Alexandra Evancho, Kevin Mammino, Courtney E Walters, Ashton Weber, Joe R Nocera","doi":"10.1177/26331055241285880","DOIUrl":"10.1177/26331055241285880","url":null,"abstract":"<p><p>The global growth of an aging population is expected to coincide with an increase in aging-related pathologies, including those related to brain health. Thus, the potential for accelerated cognitive health declines due to adverse aging is expected to have profound social and economic implications. However, the progression to pathological conditions is not an inevitable part of aging. In fact, engaging in activities that improve cardiovascular fitness appears to be a means that offers the benefits of maintaining and/or improving cognitive health in older age. However, to date, the underlying mechanisms responsible for improved central nervous system health and function with exercise are not yet fully elucidated. Consequently, there is considerable interest in studies aimed at understanding the neurophysiological benefits of exercise on aging. One such area of study suggests that the improvements in brain health via exercise are, in part, driven by the recovery of inhibitory processes related to the neurotransmitter gamma-aminobutyric acid (GABA). In the present review, we highlight the opposing effects of aging and exercise on cortical inhibition and the GABAergic system's functional integrity. We highlight these changes in GABA function by reviewing work with in vivo measurements: transcranial magnetic stimulation (TMS) and magnetic resonance spectroscopy (MRS). We also highlight recent and significant technological and methodological advances in assessing the GABAergic system's integrity with TMS and MRS. We then discuss potential future research directions to inform mechanistic GABA study targeted to improve health and function in aging. We conclude by highlighting the significance of understanding the effects of exercise and aging, its influence on GABA levels, and why a better understanding is crucial to allow for more targeted and effective interventions aimed to ultimately improve age-related decline in aging.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":"19 ","pages":"26331055241285880"},"PeriodicalIF":2.9,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11457286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}