Neuroscience Insights最新文献

{"title":"Unraveling the Connection: Cholesterol, Calcium Signaling, and Neurodegeneration.","authors":"Maria Casas, Eamonn J Dickson","doi":"10.1177/26331055241252772","DOIUrl":"10.1177/26331055241252772","url":null,"abstract":"<p><p>Cholesterol and calcium play crucial roles as integral structural components and functional signaling entities within the central nervous system. Disruption in cholesterol homeostasis has been linked to Alzheimer's, Parkinson's, and Huntington's Disease while alterations in calcium signaling is hypothesized to be a key substrate for neurodegeneration across many disorders. Despite the importance of regulated cholesterol and calcium homeostasis for brain health there has been an absence of research investigating the interdependence of these signaling molecules and how they can tune each other's abundance at membranes to influence membrane identity. Here, we discuss the role of cholesterol in shaping calcium dynamics in a neurodegenerative disorder that arises due to mutations in the lysosomal cholesterol transporter, Niemann Pick Type C1 (NPC1). We discuss the molecular mechanisms through which altered lysosomal cholesterol transport influences calcium signaling pathways through remodeling of ion channel distribution at organelle-organelle membrane contacts leading to neurodegeneration. This scientific inquiry not only sheds light on NPC disease but also holds implications for comprehending other cholesterol-associated neurodegenerative disorders.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":"19 ","pages":"26331055241252772"},"PeriodicalIF":3.6,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11088808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140913174","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":"Reporting Psychiatric Disease Characteristics in Post-Mortem- and Biological Research.","authors":"Karel Scheepstra, Mark Mizee, Dennis Wever, Cheng-Chih Hsiao, Lin Zhang, Dick Swaab, Jörg Hamann, Inge Huitinga","doi":"10.1177/26331055241252632","DOIUrl":"10.1177/26331055241252632","url":null,"abstract":"<p><p>Inflammation is a prominent hypothesis in the neurobiology of depression. In our transcriptomic profiling study of microglia in chronic major depressive disorder (MDD), we revealed a distinct disease-associated microglia (DAM) transcriptomic profile exclusively found in cortical gray matter, that we have designated DepDAM. These DepDAM revealed an immune-suppressed state, with a possible upstream mechanism for microglial suppression, by upregulation of CD200 and CD47 (\"don't eat me signals\") located on synapses. We extensively report on disease characteristics, such as cause of death, reason for euthanasia, and psychiatric state when deceased. When excluding MDD donors in a euthymic state, the trend of lower CD45 membrane expression on white matter microglia became significant, and the difference in gray matter microglia became larger. For Western blot analysis of CD47 and CD200, both means of the definitely depressed donor groups (MDD-D) increased. This underscores the utmost importance of reporting on patient and episode characteristics, such as severity, episode traits, (type of) suicidality, mode of decease, and state of illness at death in post-mortem- and biological psychiatric research. For psychiatric post-mortem research, we suggest using well-characterized donors (eg, after \"psychological autopsy\") selected by an experienced clinician.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":"19 ","pages":"26331055241252632"},"PeriodicalIF":3.6,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11088795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140913204","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":"Sex Differences in Severity and Risk Factors for Ischemic Stroke in Patients With Hyperlipidemia.","authors":"Emmanuel Imeh-Nathaniel, Samuel Imeh-Nathaniel, Adebobola Imeh-Nathaniel, Oreoluwa Coker-Ayo, Nikhil Kulkarni, Thomas I Nathaniel","doi":"10.1177/26331055241246745","DOIUrl":"https://doi.org/10.1177/26331055241246745","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to determine sex differences in poststroke hypertriglyceridemia (serum triglyceride levels ⩾ 200 mg/dl) and high stroke severity in ischemic stroke patients.</p><p><strong>Method: </strong>Our study analyzed data from 392 males and 373 females with hypertriglyceridemia. Stroke severity on admission was measured using the National Institute of Health Stroke Scale (NIHSS) with a value ⩽7 indicating a more favorable post-stroke prognosis while a score of >7 indicates poorer post-stroke outcomes. Logistic regression models adjusted for demographic and risk factors. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for each clinical risk factor were used to predict the increasing odds of an association of a specific clinical baseline risk factor with the male or female AIS with hypertriglyceridemia.</p><p><strong>Results: </strong>In the adjusted analysis, male patients with hypertriglyceridemia, diastolic blood pressure (OR = 1.100, 95% CI, 1.034-1.171, <i>P</i> = .002), and Ischemic stroke mortality (OR = 6.474, 95% CI, 3.262-12.847, <i>P</i> < .001) were significantly associated with increased stroke severity. In female patients with hypertriglyceridemia, age (OR = 0.920, 95% CI, 0.866-0.978, <i>P</i> = .008) was associated with reduced stroke severity, while ischemic stroke mortality score (OR = 37.477, 95% CI, 9.636-145.756, <i>P</i> < .001) was associated with increased stroke severity.</p><p><strong>Conclusion: </strong>Increased ischemic stroke mortality risk score was associated with increased severity in both male and female AIS patients with hypertriglyceridemia. Our findings provide information about sex differences in specific risk factors that can be managed to improve the care of male and female ischemic stroke patients with hypertriglyceridemia.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":"19 ","pages":"26331055241246745"},"PeriodicalIF":3.6,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11069268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140872641","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":"Corticospinal Modulation of Precision Movements.","authors":"Francesca Marino, Yunuen Moreno-López, Edmund Hollis","doi":"10.1177/26331055241249497","DOIUrl":"10.1177/26331055241249497","url":null,"abstract":"<p><p>Recently we demonstrated a critical role for temporal coding of corticospinal activity in a prehension movement requiring precise forelimb control. Learning of precision isometric pull drives large-scale remodeling of corticospinal motor networks. Optogenetic modulation of corticospinal activity and full transection of the corticospinal tract disrupted critical functions of the network in expert animals resulting in impaired modulation of precise movements. In contrast, we observed more widespread corticospinal co-activation and limited temporal coding on a similar, yet more simplistic prehension task, adaptive isometric pull. Disrupting corticospinal neuron activity had much more limited effects on adaptive isometric pull, which was found to be corticospinal independent by transection of the corticospinal tract. Here we discuss these results in context of known roles for corticospinal and corticostriatal neurons in motor control, as well as some of the questions our study raised.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":"19 ","pages":"26331055241249497"},"PeriodicalIF":3.6,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11056087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140853941","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":"Collateral Damage: Neurological Correlates of Non-Fatal Overdose in the Era of Fentanyl-Xylazine.","authors":"Dustin R Todaro, Nora D Volkow, Daniel D Langleben, Zhenhao Shi, Corinde E Wiers","doi":"10.1177/26331055241247156","DOIUrl":"10.1177/26331055241247156","url":null,"abstract":"<p><p>Non-fatal opioid overdoses are associated with significant morbidity. Hypoxic brain injury caused by opioid-induced respiratory depression is a key mechanism of such morbidity. For example, reports describe an amnestic syndrome in opioid users associated with acute injury to the hippocampus, a brain region that is highly susceptible to hypoxic injury. In our recent study we investigated the effects of non-fatal opioid overdose on the hippocampal volume in a well-characterized sample of opioid use disorder (OUD) patients with a history of overdose (OD) compared to those with no prior overdose (NOD). Using structural magnetic resonance imaging (MRI) and voxel-based morphometry, we observed lower hippocampal volume in patients with a history OD than in the NOD group. These findings support an association between non-fatal opioid overdose and hippocampal injury, which we hypothesize contributes to recently reported cases of OUD related amnestic syndrome. Here we review our study findings and the potential pathophysiological mechanisms underlying the acute and delayed hippocampal injury in nonfatal opioid overdose. We also discuss the implications for the risk of overdose and brain injury with the increased prevalence of fentanyl and xylazine contamination of the illicit opioid supply. Lastly, we highlight considerations for clinical management of the underappreciated neurological injury and cognitive dysfunction in OUD patients.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":"19 ","pages":"26331055241247156"},"PeriodicalIF":2.9,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11409300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142297448","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":"Expression of Concern: \"Specific Profile of Tau Isoforms in Argyrophylic Grain Disease\".","authors":"","doi":"10.1177/26331055241241673","DOIUrl":"10.1177/26331055241241673","url":null,"abstract":"","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":"19 ","pages":"26331055241241673"},"PeriodicalIF":3.6,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10953075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140176885","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":"A Vascular-Centric Approach to Autism Spectrum Disorders.","authors":"Julie Ouellette, Elizabeth E Crouch, Jean-Luc Morel, Vanessa Coelho-Santos, Baptiste Lacoste","doi":"10.1177/26331055241235921","DOIUrl":"10.1177/26331055241235921","url":null,"abstract":"<p><p>Brain development and function are highly reliant on adequate establishment and maintenance of vascular networks. Early impairments in vascular health can impact brain maturation and energy metabolism, which may lead to neurodevelopmental anomalies. Our recent work not only provides novel insights into the development of cerebrovascular networks but also emphasizes the importance of their well-being for proper brain maturation. In particular, we have demonstrated that endothelial dysfunction in autism spectrum disorders (ASD) mouse models is causally related to altered behavior and brain metabolism. In the prenatal human brain, vascular cells change metabolic states in the second trimester. Such findings highlight the need to identify new cellular and molecular players in neurodevelopmental disorders, raising awareness about the importance of a healthy vasculature for brain development. It is thus essential to shift the mostly neuronal point of view in research on ASD and other neurodevelopmental disorders to also include vascular and metabolic features.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":"19 ","pages":"26331055241235921"},"PeriodicalIF":3.6,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10929024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140111707","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 Pigeon as a Model of Complex Visual Processing and Category Learning.","authors":"Edward A Wasserman, Brandon M Turner, Onur Güntürkün","doi":"10.1177/26331055241235918","DOIUrl":"10.1177/26331055241235918","url":null,"abstract":"<p><p>Over the past 30 years, behavioral, computational, and neuroscientific investigations have yielded fresh insights into how pigeons adapt to the diverse complexities of their visual world. A prime area of interest has been how pigeons categorize the innumerable individual stimuli they encounter. Most studies involve either photorealistic representations of actual objects thus affording the virtue of being naturalistic, or highly artificial stimuli thus affording the virtue of being experimentally manipulable. Together those studies have revealed the pigeon to be a prodigious classifier of both naturalistic and artificial visual stimuli. In each case, new computational models suggest that elementary associative learning lies at the root of the pigeon's category learning and generalization. In addition, ongoing computational and neuroscientific investigations suggest how naturalistic and artificial stimuli may be processed along the pigeon's visual pathway. Given the pigeon's availability and affordability, there are compelling reasons for this animal model to gain increasing prominence in contemporary neuroscientific research.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":"19 ","pages":"26331055241235918"},"PeriodicalIF":3.6,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10903219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139997668","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":"Synergistic Effect of an Antisense Oligonucleotide and Small Molecule on Splicing Correction of the Spinal Muscular Atrophy Gene.","authors":"Eric W Ottesen, Ravindra N Singh","doi":"10.1177/26331055241233596","DOIUrl":"10.1177/26331055241233596","url":null,"abstract":"<p><p>Spinal muscular atrophy (SMA) is treated by increasing the level of Survival Motor Neuron (SMN) protein through correction of <i>SMN2</i> exon 7 skipping or exogenous expression of SMN through gene therapy. Currently available therapies have multiple shortcomings, including poor body-wide distribution, invasive delivery, and potential negative consequences due to high doses needed for clinical efficacy. Here we test the effects of a combination treatment of a splice-correcting antisense oligonucleotide (ASO) Anti-N1 with the small compounds risdiplam and branaplam. We show that a low-dose treatment of Anti-N1 with either compound produces a synergistic effect on the inclusion of <i>SMN2</i> exon 7 in SMA patient fibroblasts. Using RNA-Seq, we characterize the transcriptomes of cells treated with each compound as well as in combination. Although high doses of each individual treatment trigger widespread perturbations of the transcriptome, combination treatment of Anti-N1 with risdiplam and branaplam results in minimal disruption of gene expression. For individual genes targeted by the 3 compounds, we observe little to no additive effects of combination treatment. Overall, we conclude that the combination treatment of a splice-correcting ASO with small compounds represents a promising strategy for achieving a high level of SMN expression while minimizing the risk of off-target effects.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":"19 ","pages":"26331055241233596"},"PeriodicalIF":3.6,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10878212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139913665","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":"What Do Cancer Surgery and orthopedic Surgery Elderly Patients Have in Common? A Long-term Postoperative Cognitive Dysfunction in Orthopedic and Cancer Patients Original Research.","authors":"Kalliopi Megari, Evanthia Thomaidou, Georgios A Kougioumtzis, Maria Theodoratou, Dimitra Katsarou, Eleni Karlafti, Matthaios Didaggelos, Daniel Paramythiotis, Eleni Argyriadou","doi":"10.1177/26331055231220906","DOIUrl":"10.1177/26331055231220906","url":null,"abstract":"<p><strong>Objectives-background: </strong>Postoperative cognitive dysfunction (POCD) involves decline in several cognitive domains after surgery and is particularly common after cardiac surgery, while also common among other types of surgery. Given the potential effects of such cognitive dysfunction on the quality of life, it is important to study it in multiple populations in order to limit its occurrence.</p><p><strong>Study design: </strong>We present the long-term neuropsychological outcome of 200 patients, 100 of whom had orthopedic surgery and 100 oncological surgery.</p><p><strong>Methods: </strong>We administered a series of neuropsychological tests assessing attention, complex scanning, verbal working memory, executive functioning, short-term and long-term memory, and visuospatial perception before surgery, prior to discharge, at 3-month follow-up and 6 years after surgery. We compared the performance of these patients to normative datasets.</p><p><strong>Results: </strong>Despite equivalent levels of pre-surgery performance between patients, oncology patients exceeded their preoperative neurocognitive levels, suggesting less postoperative cognitive dysfunction in orthopedic patients overall, in all neuropsychological domains at a 6-year follow-up, except short-term retention. In contrast, orthopedic patients showed no improvement, and, instead, showed some cognitive decline, which remained consistent over time.</p><p><strong>Conclusions: </strong>Our findings highlight the critical role of the type of surgery utilized in the development of POCD and have implications for clinical management and patients' quality of life in the very long term. Health policy professionals should be aware that patients' low POCD may persist in the long term, and this is useful from a clinician's point of view.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":"19 ","pages":"26331055231220906"},"PeriodicalIF":3.6,"publicationDate":"2024-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10860461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139724392","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}