Neuroscience Insights最新文献

Repetitive Transcranial Magnetic Stimulation (rTMS) has been applied as an investigational therapy for Alzheimer's Disease (AD). The recent largest (N = 135) double-blind study with 6 months post-treatment follow-up investigating rTMS efficacy as a treatment for AD found about 72% of participants in each group of active and sham were positively responsive to rTMS (using Magstim AirFilm active and sham coils). Since the used sham coil produced about 25.3% of the peak active stimulus, it was hypothesized it could evoke a measurable response in AD patients. This study looks at the details of the above study's sham responses to determine why and how such a response might occur and how cerebrovascular symptomatology may have impacted that response. In the above-mentioned study, 90 and 45 patients were randomly assigned to active and sham groups, respectively. Those with modified Hachinski Ischemic Scores (HIS) below and above 2 were labeled AD₂ and ADcvd₂, respectively. Analysis of the primary outcome measure ADAS-Cog score change from baseline to post-treatment and follow-ups showed the ADcvd₂ in the sham group had a significantly (p = .034) greater improvement or less decline at post-treatment and follow-up sessions compared to the ADcvd₂ in the active group. Additionally, the improvement of the ADcvd₂ sham compared to those in the active group persisted longer. Also, there was a significant (p = .036) improvement for AD₂ individuals in the active compared to AD₂ sham stimulation group at 2-months post-treatment. Overall, the sham rTMS stimulus did evoke a measurable response which was more effective for ADcvd₂ in sham than ADcvd₂ in active support of a vascular mechanism likely linked to the shallower sham stimulus penetration.

Background: A previous randomized pre-post cross-over study with 26 participants found positive changes in motor and non-motor symptoms in people with Parkinson's disease (PwPD) after six weeks of group classical guitar sessions but not customary and usual treatment.

Objective: To determine if a six-week group classical guitar instruction program improved motor function, mood, and quality of life for PwPD in comparison to a six-week group exercise program in a non-randomized cross-over pilot study.

Methods: Eighteen PwPD were enrolled and 15 completed the study. Group 1 (N = 10) received a six-week group guitar instruction program, and then a six-week group exercise program. Group 2 (N = 8) received a six-week group exercise program, and then a six-week guitar instruction program. Assessments were at baseline, six weeks, and 12 weeks. The groups were combined for analysis by two-tailed paired t-tests due to the low sample size. Assessments included the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor sub-section, Hoehn and Yahr scale, Parkinson's Disease Questionnaire-39 (PDQ-39), Apathy Evaluation Scale-Self (AES-S), and Beck Depression Inventory II (BDI-II).

Results: MDS-UPDRS mean motor scores decreased compared to pre-test scores with group guitar instruction (-5.3 points, P < .001), but not group exercise (-0.47 points, P = .85). BDI-II mean scores decreased by 2.13 (P = .08) and 1.87 points (P = .02) with group guitar instruction and group exercise, respectively. PDQ-39 mean scores decreased by 1.93 (P = .02) and 2.52 (P = .02) points with group guitar instruction and group exercise, respectively. AES-S mean scores decreased with group exercise (-2.40 points, P = .03) but not group guitar instruction (-2.4 points, P = .26).

Conclusions: Group guitar instruction could potentially help with both motor and non-motor symptoms in PwPD. There appears to be a specific effect of group guitar instruction on MDS-UPDRS motor scores that is not due to regular meetings and general exercises. This unfunded study was registered at ClinicalTrials.gov (NCT05917704).

Traumatic brain injury (TBI) is a modifiable risk factor for Alzheimer's disease (AD). TBI and AD share several histopathological hallmarks: namely, beta-amyloid aggregation, tau hyperphosphorylation, and plasma protein infiltration. The relative contributions of these proteinopathies and their interplay in the pathogenesis of both conditions remains unclear although important differences are emerging. This review synthesises emerging evidence for the critical role of the neurovascular unit in mediating protein accumulation and neurotoxicity in both TBI and AD. We propose a shared pathogenic cascade centred on a neurovascular unit, in which increased blood-brain barrier permeability induces a series of noxious mechanisms leading to neuronal loss, synaptic dysfunction and ultimately cognitive dysfunction in both conditions. We explore the application of this hypothesis to outstanding research questions and potential treatments for TBI and AD, as well as other neurodegenerative and neuroinflammatory conditions. Limitations of this hypothesis, including the challenges of establishing a causal relationship between neurovascular damage and proteinopathies, are also discussed.

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.