Amelie Marie Back, Bronwen Connor, Amy McCaughey-Chapman
{"title":"Oligodendrocytes in Huntington's Disease: A Review of Oligodendrocyte Pathology and Current Cell Reprogramming Approaches for Oligodendrocyte Modelling of Huntington's Disease","authors":"Amelie Marie Back, Bronwen Connor, Amy McCaughey-Chapman","doi":"10.1002/jnr.70010","DOIUrl":"10.1002/jnr.70010","url":null,"abstract":"<div>\u0000 \u0000 <p>Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder traditionally characterized by the selective loss of medium spiny neurons in the basal ganglia. However, it has become apparent that white matter injury and oligodendrocyte dysfunction precede the degeneration of medium spiny neurons, garnering interest as a key pathogenic mechanism of HD. Oligodendrocytes are glial cells found within the central nervous system involved in the production of myelin and the myelination of axons. Myelin is a lipid-rich sheath that wraps around axons, facilitating signal conduction and neuronal viability. The degeneration of myelin hinders effective communication and leaves neurons vulnerable to external damage and subsequent degeneration. Abnormalities in oligodendrocyte maturation have been established in the HD human brain, however, investigations into the underlying dysfunction of human oligodendrocytes in HD are limited. This review will detail the involvement of oligodendrocytes and white matter damage in HD. Recent developments in modeling human-specific oligodendrocyte pathology in HD will be discussed, with a particular focus on emerging somatic cell reprogramming approaches.</p>\u0000 </div>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"102 12","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lucia Gaddini, Valentina Chiodi, Andrea Matteucci, Zaira Boussadia, Luc Buée, Sabiha Eddarkaoui, David Blum, Nazzareno Di Carlo, Carla Raggi, Rita Di Benedetto, Patrizia Popoli, Antonella Ferrante
{"title":"Dipyridamole Ameliorates Memory Impairment and Increases Hippocampal Calbindin Expression in Niemann Pick C1 Mice","authors":"Lucia Gaddini, Valentina Chiodi, Andrea Matteucci, Zaira Boussadia, Luc Buée, Sabiha Eddarkaoui, David Blum, Nazzareno Di Carlo, Carla Raggi, Rita Di Benedetto, Patrizia Popoli, Antonella Ferrante","doi":"10.1002/jnr.70011","DOIUrl":"10.1002/jnr.70011","url":null,"abstract":"<p>Niemann Pick type C1 (NPC1) is a rare, fatal disorder characterized by endosomal lipid accumulation that leads to damage of both peripheral organs and central nervous system (cerebellum and hippocampus are especially affected). Currently, miglustat is the only approved drug for NPC1, thus the identification of new treatments is mandatory. We have previously demonstrated that the drug dipyridamole (DIP), an enhancer of adenosine signaling, can reduce the pathological phenotype in patient-derived fibroblasts. In this paper, we evaluated the <i>in vivo</i> effects of DIP in NPC1 mice. Male and female NPC1<sup>nih</sup> mice were treated with DIP 30 mg/kg i.p. from 28 to 64 days of age. Motor function was assessed by Erasmus Ladder test, hippocampal cognitive decline by Novel Object Recognition test and brain pathology by immunofluorescence and biochemical assays. Peripheral pathology was evaluated by analyzing lipid accumulation in spleen and liver (HP-TLC). In NPC1, mice DIP rescued recognition memory and increased hippocampal expression of calbindin. On the contrary, the drug was unable to improve motor function, cerebellar pathology and lipid accumulation in spleen and liver. Our results demonstrated that DIP selectively ameliorates the cognitive impairment in NPC1 mice. This drug could thus represent a valuable therapeutic tool to be used in combination with other treatments in NPC1.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"102 12","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jnr.70011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Engrailed1 in Parvalbumin-Positive Neurons Regulates Eye-Specific Retinogeniculate Segregation and Visual Function","authors":"Yuqing Chen, Chengyong Jiang, Biao Yan, Jiayi Zhang","doi":"10.1002/jnr.70007","DOIUrl":"10.1002/jnr.70007","url":null,"abstract":"<div>\u0000 \u0000 <p>Homeobox transcription factor Engrailed1 (En1) is expressed in the ectoderm and mediates the establishment of retinotectal topography, but its role in eye-specific retinogeniculate segregation and visual function remains unclear. Parvalbumin (PV) neurons, which are widely distributed in the visual pathway, play a crucial role in visual development and function. In this study, we conditionally knocked out En1 gene in PV neurons and found an expansion of the ipsilateral eye projection, while no significant effects were observed in the contralateral eye projection. Additionally, we observed a decrease in the number of PV neurons in PV-Cre:En1<sup>fl/fl</sup> mice, accompanied by an increased level of cleaved caspase-3 in PV neurons. Furthermore, the genetic ablation of PV neurons in the retina through intraocular AAV-DIO-Caspase3 injection in PV-Cre mice was sufficient to disrupt retinogeniculate segregation. Finally, we observed that PV-Cre:En1<sup>fl/fl</sup> mice exhibited enhanced visual depth perception in the visual cliff test. These results demonstrate that En1 in PV neurons participates in eye-specific retinogeniculate segregation through cell survival and regulates binocular vision.</p>\u0000 </div>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"102 12","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Justin Bellavance, Laurence S. David, Michael E. Hildebrand
{"title":"An Open-Source Tool for Investigation of Differential RNA Expression Between Spinal Cord Cells of Male and Female Mice","authors":"Justin Bellavance, Laurence S. David, Michael E. Hildebrand","doi":"10.1002/jnr.70008","DOIUrl":"10.1002/jnr.70008","url":null,"abstract":"<p>Chronic pain is a highly debilitating condition that differs by type, prevalence, and severity between men and women. To uncover the molecular underpinnings of these differences, it is critical to analyze the transcriptomes of spinal cord pain-processing networks for both sexes. Despite several recently published single-nucleus RNA-sequencing (snRNA-seq) studies on the function and composition of the mouse spinal cord, a gene expression analysis investigating the differences between males and females has yet to be performed. Here, we combined data from three different large-scale snRNA-seq studies, which used sex-identified adult mice. Using SeqSeek, we classified more than 37,000 unique viable cells within predicted cell types with the use of machine learning. We then utilized DESeq2 to identify significant differentially expressed genes (DEGs) between males and females in a variety of cell populations, including superficial dorsal horn (SDH) neurons. We found a large number of DEGs between males and females in all cells, in neurons, and in SDH neurons of the mouse spinal cord, with a greater level of differential expression in inhibitory SDH neurons compared to excitatory SDH neurons. The results of these analyses are available on an open-source web-app: https://justinbellavance.shinyapps.io/snRNA_Visualization/. Lastly, we used gene set enrichment analysis to identify sex-enriched pathways from our previously identified DEGs. Through this, we have identified specific genetic players within the rodent spinal cord that diverge between males and females, which may underlie reported sex differences in spinal nociceptive mechanisms and pain processing.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"102 12","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11645520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sydney E. Lee, Sung-Hoon Park, John C. Aldrich, Laura K. Fonken, Andrew D. Gaudet
{"title":"Anxiety-Like Behaviors in Mice Unmasked: Revealing Sex Differences in Anxiety Using a Novel Light-Heat Conflict Test","authors":"Sydney E. Lee, Sung-Hoon Park, John C. Aldrich, Laura K. Fonken, Andrew D. Gaudet","doi":"10.1002/jnr.70002","DOIUrl":"10.1002/jnr.70002","url":null,"abstract":"<div>\u0000 \u0000 <p>Anxiety and chronic pain afflict hundreds of millions worldwide. Anxiety and pain are more prevalent in females compared to males. Unfortunately, robust sex differences in human anxiety are not recapitulated in rodent tests, and results from rodent pain studies frequently fail to translate clinically. Therefore, there is a need to develop tests that reflect the differential salience of anxiety or pain-related stimuli between the sexes. Accordingly, here we introduce the Thermal Increments Dark–Light (TIDAL) conflict test. The TIDAL test places an anxiety-relevant stimulus (dark vs. illuminated chamber) in conflict with a heat-related stimulus (incrementally heated vs. isothermic chamber); mice freely explore both apparatus chambers. Here, we aim to determine whether the TIDAL conflict test reveals in mice underappreciated sex differences in anxiety and/or heat sensitivity. We establish in four distinct experiments that females on the TIDAL conflict test persist substantially longer on the dark-heated plate, suggesting that female mice exhibit elevated anxiety-like behavior. Mice more strongly prefer the heated-dark plate on the TIDAL conflict test compared to control thermal place preference with both chambers illuminated. We also reveal that an anxiety-relieving drug, paroxetine, reduces mouse preference for the heating dark plate, supporting the validity of the TIDAL test. Therefore, our new TIDAL conflict test reliably unmasks the relative salience of anxiety (vs. heat sensitivity): mice that are female exhibit robust anxiety-like behaviors not consistently observed in classical tests. Future studies should incorporate TIDAL and other conflict tests to better understand rodent behavior and to identify mechanisms underlying anxiety and pain.</p>\u0000 </div>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"102 12","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to “What Do Brain Oscillations Tell About the Human Sense of Smell?”","authors":"","doi":"10.1002/jnr.70009","DOIUrl":"10.1002/jnr.70009","url":null,"abstract":"<p>Mignot, C., Weise, S., Podlesek, D., Leonhardt, G., Bensafi, M., & Hummel, T. (2024). What do brain oscillations tell about the human sense of smell? <i>Journal of Neuroscience Research</i>, <i>102</i>, e25335. https://doi.org/10.1002/jnr.25335</p><p>In Figure 1, some of the labels in the panel summarizing the different brain structures involved in smell processing were incorrectly placed.</p><p>The corrected figure and caption appear below.</p><p>We apologize for the error.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"102 12","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jnr.70009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Neurologic Music Therapy's Impact on Neurological Disorders","authors":"Yaming Wei, Zhen Qiao","doi":"10.1002/jnr.70000","DOIUrl":"https://doi.org/10.1002/jnr.70000","url":null,"abstract":"<div>\u0000 \u0000 <p>Neurologic music therapy (NMT) represents a groundbreaking, interdisciplinary approach that combines the therapeutic properties of music with neuroscientific principles to treat a range of neurological and psychiatric conditions. This interdisciplinary approach, increasingly recognized in clinical and research settings, leverages advances in neuroimaging to explore how music affects the structure and activity of the brain. This review provides an in-depth exploration of the multifaceted effects of NMT on brain function, highlighting its role in promoting neuroplastic changes and enhancing cognitive, emotional and motor functions in diverse patient groups. This review consolidates current knowledge on NMT and provides insights into how music affects brain structure and function and the mechanisms of action. The article then discusses the application and research results of NMT in various diseases such as stroke, Alzheimer's disease and Parkinson's disease. Its potential in personalizing therapeutic interventions and its ability to improve treatment access and effectiveness in various settings are highlighted.</p>\u0000 </div>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"102 12","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maggie E. Baird, Richard Beare, Marc L. Seal, Joseph Yuan-Mou Yang, Jacqueline F. I. Anderson
{"title":"Mild Traumatic Brain Injury Is Associated With Increased Thalamic Subregion Volume in the Subacute Period Following Injury","authors":"Maggie E. Baird, Richard Beare, Marc L. Seal, Joseph Yuan-Mou Yang, Jacqueline F. I. Anderson","doi":"10.1002/jnr.70004","DOIUrl":"https://doi.org/10.1002/jnr.70004","url":null,"abstract":"<div>\u0000 \u0000 <p>Structural vulnerability of the thalamus remains underinvestigated in mild traumatic brain injury (mTBI), and few studies have addressed its constituent nuclei using robust segmentation methods. This study aimed to investigate thalamic subnuclei volume in the subacute period following mTBI. Trauma control (TC) and mTBI patients aged 18–60 years old completed a magnetic resonance imaging (MRI) protocol including both high resolution structural (T1w) and diffusion-weighted sequences at 6–12 weeks following injury (mean: 57 days; SD 11). Each thalamus was segmented into its constituent subnuclei, which were grouped into eight lateralized subregions. Volumes of the subregions were calculated. Neurite Orientation Dispersion and Density (NODDI) maps with parameters optimized for gray matter were computed for the same subregions. Group differences in subregion volumes and NODDI parameters were investigated using Bayesian linear modeling, with age, sex, and estimated intracranial volume included as covariates. Comparisons of mTBI (<i>n</i> = 39) and TC (<i>n</i> = 28) groups revealed evidence of relatively increased gray matter volume in the mTBI group for the bilateral medial and right intralaminar subregions (BF<sub>10</sub> > 3). Of the subregions which showed volume differences, there was no evidence for differences in NODDI metrics between groups. This study demonstrates that in the subacute period following mTBI, there is evidence of increased volume in specific thalamic subregions. Putative mechanisms underpinning the increased volume observed here are disordered remyelination or myelin debris yet to be cleared.</p>\u0000 </div>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"102 12","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhu-Qing Zhang, Dan Liao, Zhi-Peng Guo, Shuang-Shuang Song, Xue-Jun Liu
{"title":"Aberrant Dynamic Network Connectivity Changes in Comorbid Depression and Overweight/Obesity: Insights From the Triple Network Model","authors":"Zhu-Qing Zhang, Dan Liao, Zhi-Peng Guo, Shuang-Shuang Song, Xue-Jun Liu","doi":"10.1002/jnr.70001","DOIUrl":"https://doi.org/10.1002/jnr.70001","url":null,"abstract":"<div>\u0000 \u0000 <p>The interaction between major depressive disorder (MDD) and overweight/obesity has received considerable attention owing to its widespread occurrence and the intricate biopsychological implications involved. Despite extensive research, the neural mechanisms underlying these comorbid conditions, particularly in terms of functional network connectivity (FNC), are still not well understood. This study aimed to clarify these mechanisms by utilizing resting-state functional magnetic resonance imaging (rs-fMRI) to examine both static and dynamic FNC. We analyzed data from 57 patients with both MDD and overweight/obesity (MDD-OW), 57 MDD patients of normal weight (MDD-NW), and 44 healthy controls, using techniques such as independent component analysis, sliding window analysis, K-means clustering, and graph theory. In contrast to static FNC, which showed no significant differences, dynamic FNC analysis identified four consistent states across all participants. Both MDD groups demonstrated reduced flexibility in functional coordination among these states and decreased nodal characteristics within the salience network. Notably, the MDD-OW group displayed enhanced dynamic FNC between the default mode network (DMN) and the executive control network (ECN) during certain states, which was inversely associated with the severity of depressive symptoms. These results highlight the importance of altered dynamic connectivity patterns in individuals with MDD and concurrent overweight/obesity, especially between the DMN and ECN, suggesting their potential utility as biomarkers for depressive states. This research contributes to our understanding of how comorbid overweight/obesity affects brain network dynamics in depressive disorders and provides a basis for targeted therapeutic strategies.</p>\u0000 </div>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"102 12","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Decreased Water Diffusivity Along the Perivascular Space in Older Adults With Poor Sleep Quality","authors":"Junko Kikuta, Koji Kamagata, Kaito Takabayashi, Yayoi Hayakawa, Toshiaki Taoka, Yuya Saito, Wataru Uchida, Sen Guo, Seina Yoshida, Keigo Yamazaki, Akihiko Wada, Hideyoshi Kaga, Yoshifumi Tamura, Ryuzo Kawamori, Hirotaka Watada, Shigeki Aoki","doi":"10.1002/jnr.70005","DOIUrl":"https://doi.org/10.1002/jnr.70005","url":null,"abstract":"<div>\u0000 \u0000 <p>This study included 52 Japanese older adults with Pittsburgh Sleep Quality Index (PSQI) scores > 5 and 52 healthy controls (HCs) with PSQI score ≤ 5. Diffusion-weighted imaging (DWI) and 3D T1-weighted imaging were acquired using 3T magnetic resonance imaging. The diffusion tensor image analysis along the perivascular space (DTI-ALPS) index was calculated using preprocessed DWI. The choroid plexus volume (CPV) was calculated using FreeSurfer 6.0. The mean ALPS index and CPV were compared between the older adults with poor sleep quality (PSQ) and HCs using a general linear model, adjusted for covariates including age, sex, years of education, total intracranial volume, systolic blood pressure, hemoglobin A1c, and white matter lesion volume. We also conducted a partial correlation analysis between the mean ALPS index and CPV, Montreal Cognitive Assessment (MoCA), and PSQI scores, adjusting for all the mentioned covariates. The PSQ group had a significantly lower mean ALPS index than HCs. The mean ALPS index in the PSQ group was negatively correlated with CPV and positively correlated with the MoCA score. Therefore, older adults with PSQ may experience dysfunction in the excretory pathway of the perivascular space around the medullary veins. This impairment may be associated with an increase in CPV and cognitive dysfunction.</p>\u0000 </div>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"102 12","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}