Neuroscience Insights最新文献

{"title":"Synaptic Chaperone Dysfunction as a Convergent Mechanism in Neurodegenerative and Psychiatric Disorders.","authors":"Danielle Jean, Yun Li","doi":"10.1177/26331055261424760","DOIUrl":"10.1177/26331055261424760","url":null,"abstract":"<p><p>The heat shock protein (HSP) family comprises six sub-families whose members participate in a wide array of cellular processes. This minireview focuses on three specific heat shock proteins: Hsp90aa and Hsp90ab from the Hsp90 sub-family, Hsc70 (Hspa8) from the Hsp70 sub-family, and the Hsp40 co-chaperone sub-family. In neuronal cells, these HSPs play critical roles in maintaining proper synaptic proteostasis. We have summarized current evidence for how these HSPs act independently and collaboratively to maintain synaptic proteostasis. Importantly, emerging data suggests that synaptic disruptions of Hsp90, Hsc70, or their Hsp40 partners not only contribute to hallmarks of neurodegenerative pathology but also contribute to psychiatric conditions such as depression and post-traumatic stress disorder (PTSD). By integrating findings across these two disease categories, we propose that dysfunctional chaperones at the synapse represent a molecular link between neurodegenerative and neuropsychiatric disorders.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":"21 ","pages":"26331055261424760"},"PeriodicalIF":3.5,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12954018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147356817","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":"Stage-Dependent Function of Astrocytes in Alzheimer's Disease: A Review.","authors":"Helya Bolouki Azari, Parvin Babaei, Mobina Taghva Nakhjiri","doi":"10.1177/26331055261422166","DOIUrl":"10.1177/26331055261422166","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by extracellular amyloid beta (Aβ) plaques, intracellular neurofibrillary tangles (NFTs), astrogliosis, loss of neurons, and cognitive decline. In this narrative review, we explore astrocytes' dual role in the healthy brain and the brain with AD, reflecting on the available human studies and animal models. Astrocytes are multifunctional regulators of brain homeostasis and neuronal activity within the central nervous system (CNS). These highly plastic cells undergo morphological and functional changes in response to the progression of AD, and exhibit dynamic, stage-dependent phenotypes. In the early stage of AD, astrocytes adopt a predominantly neuroprotective A2 phenotype, marked by enhanced glycolysis, Aβ clearance, anti-inflammatory signaling, and synaptic support. At the intermediate stage, they shift toward an inflammatory phenotype, which consequently impairs metabolism and neurotransmitter uptake. In the late stage of AD, the A1 phenotype, characterized by inflammatory cytokine secretion, complement activation, Ca dysregulation, and mitochondrial toxicity, exacerbates AD progression. Thus, the balance between these subtypes can significantly influence the disease's trajectory, with A1 astrocytes contributing to neurotoxicity and A2 astrocytes providing neuroprotection, especially in the early stages.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":"21 ","pages":"26331055261422166"},"PeriodicalIF":3.5,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12932886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147310949","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":"Comprehensive Proteomic Profiling of Human Nav1.7-Interacting Proteins Reveals Conserved Regulatory Networks Involved in Nociceptive Signaling.","authors":"Xuelong Zhou, Jing Zhao","doi":"10.1177/26331055251405071","DOIUrl":"10.1177/26331055251405071","url":null,"abstract":"<p><p>The voltage-gated sodium channel Nav1.7, encoded by the SCN9A gene, is critically involved in the initiation and propagation of nociceptive signals. While prior research has delineated the interactome of mouse Nav1.7 (mNav1.7), the molecular partners associated with its human homolog (hNav1.7) remain largely undefined. In this study, we employed tandem affinity purification (TAP) combined with high-resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS) to systematically characterize the protein-protein interaction (PPI) network of hNav1.7 in stably transfected HEK293 cells. Functional expression of TAP-tagged hNav1.7 was confirmed by immunofluorescence, immunoblotting, and whole-cell patch-clamp electrophysiology. A total of 261 interacting proteins were identified, primarily localized to the plasma membrane and cytoplasm, and predominantly enriched in protein translation, folding, and trafficking pathways. Comparative proteomic analysis revealed conserved interactors shared between human and mouse Nav1.7, including translation elongation factors (Eef1a1, Eef2), chaperonin subunits (CCT2, CCT3, CCT5, CCT6A, CCT7), and members of the kinesin and Rab GTPase families. Knockdown of 2 conserved interactors, CCT5 and TMED10, significantly reduced hNav1.7 current density, confirming their functional relevance. These findings provide new insights into the proteomic architecture and regulatory mechanisms of hNav1.7, offering potential targets for modulating channel function in pain pathophysiology.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":"20 ","pages":"26331055251405071"},"PeriodicalIF":2.6,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12698995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145757935","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":"Investigating Prospective Memory Processes: ERP Evidence from Novel Semantic Judgment Tasks.","authors":"Eliza Baby, Shraddha A Shende, Sally Grace Rogers, Natalia Rzepa, Raksha A Mudar","doi":"10.1177/26331055251393541","DOIUrl":"10.1177/26331055251393541","url":null,"abstract":"<p><p>Prospective memory (PM), the ability to plan and execute intentions in the future, plays a critical role in managing everyday tasks. A gap exists in our understanding of the neural mechanisms underlying PM retrieval based on semantic judgment, particularly when using picture-based stimuli. The current study tested 2 novel picture-based semantic-judgment PM tasks: Animal-cued Prospective Retrieval Task (Ac-PRT) and Object-cued Prospective Retrieval Task (Oc-PRT), designed to investigate PM processes involved in intention formation (Cue trials), intention retention (Ongoing trials), and intention retrieval (PM Retrieval trials). Twenty-three young adults, aged 18 to 30 years, completed the tasks while EEG data were recorded. Behavioral results showed that participants responded more slowly during Ongoing trials compared to Cue and PM Retrieval trials and were less accurate during PM Retrieval trials. Additionally, between the tasks, responses were faster and more accurate in Ac-PRT than in Oc-PRT during both Ongoing and PM Retrieval trials. ERP analyses revealed distinct neural signatures across trial types, particularly in P2, N2, N4, and Parietal Positivity (PP) components in both tasks. Additionally, task-specific differences were observed during the PM Retrieval trials in P2, N4, and PP amplitudes and in PP amplitude during the Ongoing trials. These findings demonstrate that the 2 tasks effectively dissociated core PM processes and showed category-specific differences in behavioral and neural mechanisms, offering a robust framework for future investigations of PM in aging and clinical populations.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":"20 ","pages":"26331055251393541"},"PeriodicalIF":2.6,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12639234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145589081","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":"Sciatic Nerve Electrical Stimulation Enhances Locomotor Recovery in Rats Following Spinal Cord Contusion.","authors":"Shih-Yen Tsai, Jennifer A Schreiber, Jordan Iordanou, Son T Ton, Akram Imam, Brian E Powers, James S Walter, Martin Oudega, Gwendolyn L Kartje, Russ P Nockels","doi":"10.1177/26331055251385592","DOIUrl":"10.1177/26331055251385592","url":null,"abstract":"<p><p>Spinal cord injury affects over 300 000 individuals in the United States with limited treatment options for significant locomotor functional recovery. While functional electrical stimulation devices to assist reciprocal muscle contraction during movement are used in rehabilitation, their efficacy as a standalone treatment for direct nerve stimulation remains unclear.</p><p><strong>Objective: </strong>This study investigated the effects of direct bilateral sciatic nerve stimulation on functional recovery in an adult rat model of thoracic spinal cord contusion.</p><p><strong>Method: </strong>Twenty adult male Long Evans rats underwent T10 spinal cord contusion. Custom stimulator electrode cuffs were placed around bilateral sciatic nerves in the hindlimbs. Rats received electrical stimulation or sham stimulation for 30 minutes per day (Monday-Friday) over 6 weeks. Functional outcome was assessed weekly using the BBB locomotor scale.</p><p><strong>Results: </strong>Both groups showed normal hindlimb function pre-surgery (BBB score 21) and significant decline post-SCI and prior to stimulation. Rats in the stimulation group demonstrated significantly better BBB scores than the sham group over time (repeated measures 2-way ANOVA, <i>P</i> < .001).</p><p><strong>Conclusion: </strong>Daily bilateral sciatic nerve stimulation resulted in accelerated and significant improvement in hindlimb function after SCI compared to sham stimulation, as evaluated by BBB scores. Further research is needed to elucidate the underlying mechanisms of this effect.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":"20 ","pages":"26331055251385592"},"PeriodicalIF":2.6,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12554933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145393570","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 CHD Protein, Kismet, Restricts Synaptic BMP Signaling at Glutamatergic Synapses.","authors":"Rachel A Klaustermeier, Emily L Hendricks, Joshua A Preston, Faith L W Liebl","doi":"10.1177/26331055251379496","DOIUrl":"10.1177/26331055251379496","url":null,"abstract":"<p><p>CHD7 and CHD8 are chromatin remodeling proteins that regulate several neurodevelopmental events. Mutations in these chromatin remodeling genes occur in neurodevelopmental disorders including CHARGE Syndrome and Autism Spectrum Disorders. Kismet (Kis) is the sole <i>Drosophila</i> homolog of CHD7 and CHD8. We investigated the possibility that Kis influences retrograde synaptic signaling given that Kis restricts the synaptic levels of several cell adhesion molecules and facilitates endocytosis. Our data indicate that Kis restricts synaptic pMad while facilitating the localization of pMad to presynaptic motor neuron nuclei. While the increase in pMad at <i>kis</i> mutant synapses may contribute to the loss of Endophilin B, it may not influence the mislocalization of glutamate receptors relative to active zones or the locomotor phenotypes observed in <i>kis</i> mutants. Kis may antagonize Polycomb Repressive Complex 2 (PRC2) signaling to restrict synaptic pMad. Kis, including its chromatin remodeling/ATPase activity, is required in presynaptic motor neurons for proper synaptic pMad levels. In contrast, an ATPase-deficient Kis can rescue synaptic pMad when expressed in all tissues. Similarly, expression of human CHD7 in all tissues of <i>kis</i> mutants rescues synaptic pMad. Our data suggest a model where Kis restricts synaptic pMad both by transcription-dependent and transcription-independent mechanisms. These data may aid in a better understanding of the importance of chromatin remodeling for synaptic structure and function and the molecular changes correlated with neurodevelopmental disorders.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":"20 ","pages":"26331055251379496"},"PeriodicalIF":3.5,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12457766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145151145","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":"Open Field Two-Texture Preference Testing Is Not Associated With the Neuropathic Pain-Like Phenotype That Occurs Following Mouse Cervical Contusion Spinal Cord Injury.","authors":"David A Jaffe, Megan A Lyttle, Angelo C Lepore","doi":"10.1177/26331055251361442","DOIUrl":"10.1177/26331055251361442","url":null,"abstract":"<p><p>Development of neuropathic pain (NP) is one of the major complications associated with spinal cord injury (SCI). While well-established methods such as von Frey mechanical and facial grimace testing are often used to assess SCI-induced NP-like behaviors in animal models, these assays have significant limitations, including experimenter bias and long periods of active testing and analysis. To address these challenges, we aimed to develop a novel open field 2-texture preference test (TTPT) to assess NP-like behaviors following unilateral C5 hemicontusion SCI in mice. To do so, we modified the open field apparatus by introducing both a rough and a smooth texture to different portions of the chamber floor based on the hypothesis that the abrasive rough surface would differentially elicit NP-like avoidance behavior. However, at both pre-injury baseline and following SCI, mice spent more time and traveled a greater distance on the rough compared to smooth surface. Additionally, the TTPT did not show any correlation with von Frey or grimace data obtained from the same animals. While this novel test may be able to provide information pertaining to other components of functional outcome, the assay is not associated with the persistent NP-like phenotype that occurs following SCI.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":"20 ","pages":"26331055251361442"},"PeriodicalIF":2.6,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12317162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144776391","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":"Widespread neuronal activity related to bimanual coordination in non-human primates: evidence from Fos-like activation during bimanual versus unimanual motor task.","authors":"Yu Liu, Eric M Rouiller","doi":"10.1177/26331055251352807","DOIUrl":"10.1177/26331055251352807","url":null,"abstract":"<p><p>Electrophysiological data support the notion that spatial and temporal coordination between the forelimbs in primates takes place in a wide network of cortical and subcortical brain structures. However, single neuron electrophysiology is biased towards large, long distance projecting neurons. The aim of the present study was to assess whether the same neural network is involved when small and medium size neurons are considered. To address this issue, neuronal activity with cellular resolution was investigated and quantified using the c-fos mapping technique, targeting small and medium size diameter neurons, in adult non-human primates. Two male macaque monkeysⁱ were trained to perform a reach and grasp drawer task, executed either bimanually (BIM) or unimanually (UNI). Extensive single unit electrophysiological recordings were conducted in these two monkeys over a two-year period, preceding a final terminal c-fos session during which one monkey (Mk-1) performed exclusively the BIM task, while the second monkey (Mk-2) performed the UNI task only (250 trials each). One additional monkey (control Mk-3) did not perform any task. Fos-like immunoreactivity (FLI) was significantly higher in both Mk-1 and Mk-2 in motor brain areas than in the control monkey, demonstrating that motor activity triggered c-fos. Although the overall muscle activity was roughly comparable in both tasks, Mk-1 (BIM) exhibited a clearly stronger FLI than Mk-2 all along the rostrocaudal axis of the primary, supplementary and cingulate motor cortices, as well as the striatum. In contrast, Mk-1 and Mk-2 displayed a comparable FLI in non-motor regions, such as the visual and auditory thalamus. The present study, a very rare c-fos mapping investigation conducted in macaques performing a complex behavioral task, suggests that small and medium size (local) neurons may also contribute to the specific neural activity responsible for precise interlimb coordination, within a network associating motor cortical areas and the basal ganglia.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":"20 ","pages":"26331055251352807"},"PeriodicalIF":3.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12209580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144545180","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 Flipons, Infections, and Amyloids that Foreshadow the Fading Memories of Alzheimer's Disease.","authors":"Alan Herbert","doi":"10.1177/26331055251338815","DOIUrl":"10.1177/26331055251338815","url":null,"abstract":"<p><p>Our memories are almost magical. We can experience an event for a short moment in time and quickly recall it decades later. This review explores the impact of some relatively new discoveries in the field of flipon biology that provide insight into diseases associated with impaired memory function. I examine how an ancient immune system based on Z-DNA and Z-RNA (collectively called ZNAs) regulates pathways that impact the memories modeled by synapses. The outcomes depend on intracellular defenses activated by endogenous retroelements (ERE) and virus, and on extracellular responses to ZNAs in bacterial biofilms. The bacterial amyloids and complement activation pathways further exacerbate the decline of cognitive and affective functions by inducing remodeling of synapses. In addition to immune EREs, a class of memory EREs potentially acts as ribotransmitters. These RNAs are transported across the synapse to program the connections between neurons that underlie the formation and remodeling of memories. Examples exist of ribotransmitters derived from ERE transcripts and assembled into capsids capable of transsynaptic transmission. In contrast, the immune EREs protect the nervous system by dismantling synapses to prevent viruses and retrotransposons from crossing them. The complexity of the interactions between memory and immune EREs likely give rise to the inverted U-shaped dose-response curves for the therapeutics currently available to treat cognitive decline. Other approaches for disease prevention are suggested, along with those that promote the regeneration and reprogramming of neuronal circuits.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":"20 ","pages":"26331055251338815"},"PeriodicalIF":2.9,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12144360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250075","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":"Rare Copy Number Variants Intersecting Parkinson's-associated Genes in a Cohort of children With Autism Spectrum Disorders.","authors":"Alina Erbescu, Sorina Mihaela Papuc, Magdalena Budișteanu, Maria Dobre, Catrinel Iliescu, Mihail Eugen Hinescu, Aurora Arghir, Monica Neagu","doi":"10.1177/26331055251334595","DOIUrl":"10.1177/26331055251334595","url":null,"abstract":"<p><p>Autism spectrum disorders (ASDs) are neurodevelopmental conditions characterized by important clinical and genetic heterogeneity. Recent studies suggested an overlap between ASD and Parkinson's disease (PD) in terms of clinical manifestation and underlying genetic defects. Our aim was to assess using a chromosomal microarray assay the frequency of rare exonic deletions that overlap with PD associated genes in a pediatric ASD group. Three hundred and five children diagnosed with ASD were enrolled in a study focused on deep phenotyping and genomic profiling by chromosomal microarrays. In the investigated group, four children with ASD harbored deletions encompassing genes involved in Mendelian forms of PD or contributing to PD risk. Deletions of Parkin RBR E3 ubiquitin protein ligase (<i>PRKN)</i> and synuclein alpha interacting protein (<i>SNCAIP</i>) were found in one patient, each; two other patients showed intragenic deletions of Rab9 effector protein with kelch motifs (<i>RABEPK</i>). Our study found that deletions involving genes associated with PD are rare events, as we identified approximately 1% in the ASD cohort of children. Our data adds to the previous reports of rare genomic imbalances of PD associated genes in ASD, further supporting the hypothesis that these conditions might share molecular mechanisms of pathogenesis.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":"20 ","pages":"26331055251334595"},"PeriodicalIF":2.9,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12138218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144235454","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}