Journal of experimental neurology最新文献

{"title":"Impact of Cellular Senescence on Neurodegenerative Diseases during the COVID-19 Pandemic: Sui table Targets Required to Eliminate Cellular Senescence","authors":"M. Mohiuddin, K. Kasahara","doi":"10.33696/neurol.2.046","DOIUrl":"https://doi.org/10.33696/neurol.2.046","url":null,"abstract":"We recently reviewed the scientific literature that elucidates the impact of cellular senescence on COVID-19 complications [1]. Recent studies have discussed the association of cellular senescence in COVID-19 patients with neurodegenerative diseases [2-5]. Therefore, in the present study, we extend this scientific synopsis to comment on how cellular senescence can promote neurodegenerative diseases and to describe suitable targets for eliminating cellular senescence.","PeriodicalId":73744,"journal":{"name":"Journal of experimental neurology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43169043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Spread of Spectrin in Ataxia and Neurodegenerative Disease","authors":"J. Morrow, Michael C. Stankewich","doi":"10.33696/neurol.2.045","DOIUrl":"https://doi.org/10.33696/neurol.2.045","url":null,"abstract":"Experimental and hereditary defects in the ubiquitous scaffolding proteins of the spectrin gene family cause an array of neuropathologies. Most recognized are ataxias caused by missense, deletions, or truncations in the SPTBN2 gene that encodes beta III spectrin. Such mutations disrupt the organization of post-synaptic receptors, their active transport through the secretory pathway, and the organization and dynamics of the actin-based neuronal skeleton. Similar mutations in SPTAN1 that encodes alpha II spectrin cause severe and usually lethal neurodevelopmental defects including one form of early infantile epileptic encephalopathy type 5 (West syndrome). Defects in these and other spectrins are implicated in degenerative and psychiatric conditions. In recent published work, we describe in mice a novel variant of alpha II spectrin that results in a progressive ataxia with widespread neurodegenerative change. The action of this variant is distinct, in that rather than disrupting a constitutive ligand-binding function of spectrin, the mutation alters its response to calcium and calmodulin-regulated signaling pathways including its response to calpain activation. As such, it represents a novel spectrinopathy that targets a key regulatory pathway where calcium and tyrosine kinase signals converge. Here we briefly discuss the various roles of spectrin in neuronal processes and calcium activated regulatory inputs that control its participation in neuronal growth, organization, and remodeling. We hypothesize that damage to the neuronal spectrin scaffold may be a common final pathway in many neurodegenerative disorders. Targeting the pathways that regulate spectrin function may thus offer novel avenues for therapeutic intervention.","PeriodicalId":73744,"journal":{"name":"Journal of experimental neurology","volume":"2 1","pages":"131 - 139"},"PeriodicalIF":0.0,"publicationDate":"2021-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48739559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neural Population Computing: Parallel Distributed Processing, the Basal Ganglia, and Evolution","authors":"S. Nadeau","doi":"10.33696/neurol.2.038","DOIUrl":"https://doi.org/10.33696/neurol.2.038","url":null,"abstract":"It has been known for some time that representations in the central nervous system (CNS) are population encoded, that is, encoded as patterns of activity involving very large numbers of highly interconnected neurons in one or more neural networks extending over large expanses of the brain [1-11]. Nonetheless, understanding the computational processes occurring in pools of cortical neurons and the subcortical nuclei with which they interact continues to be one of the major challenges facing systems neuroscience.","PeriodicalId":73744,"journal":{"name":"Journal of experimental neurology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45821520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of B2-AR, TLR2, PICALM, and BDNF Gene Variants in Iranian Alzheimer’s Patients and Their Response to Rivastigmine","authors":"Parvin Mohabattalab, F. R. Rad, H. Zamani, Fariba Shirvani, M. Zamani","doi":"10.33696/neurol.2.041","DOIUrl":"https://doi.org/10.33696/neurol.2.041","url":null,"abstract":"Alzheimer’s disease (AD) is a devastating neurodegenerative disorder with polygenic and multifactorial inheritance, determined by progressive loss of memory and other cognitive functions. AD is characterized by hallmark pathological changes such as extracellular aggregation of amyloid β (Aβ), intraneuronal neurofibrillary tangles that lead to brain atrophy and loss of neural tissue [1,2]. Alzheimer’s disease is categorized according to the age of onset as early-onset (EOAD) or lateonset AD (LOAD) [3]. And, based on family history, it is classified as sporadic (SAD) or familial Alzheimer’s disease (FAD) [4]. There are various genetic and environmental factors involved in the pathogenesis of AD which makes the etiology of the disease complicated however, testing for Abstract","PeriodicalId":73744,"journal":{"name":"Journal of experimental neurology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42297986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Commentary on Vulnerability and Resilience to Activity-Based Anorexia and the Role of Dopamine.","authors":"Jeff A Beeler,&nbsp;Nesha S Burghardt","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Activity-based anorexia (ABA) is a commonly used rodent model of anorexia nervosa that is based on observations made in rats decades ago. In recently published work, we describe using this paradigm to model vulnerability and resilience to anorexia nervosa in mice, where vulnerability is characterized by hyperactivity and life-threatening weight loss and resilience is characterized by adaptation and weight stabilization. Using genetically modified hyperdopaminergic mice, we also demonstrate that increased dopamine augments vulnerability to ABA. Here, we briefly review our findings and discuss how obtaining vulnerable and resilient phenotypes enhances utility of the ABA model for understanding the neurobiological basis of anorexia nervosa. We comment on our dopamine findings and close by discussing implications for clinical treatment.</p>","PeriodicalId":73744,"journal":{"name":"Journal of experimental neurology","volume":" ","pages":"21-28"},"PeriodicalIF":0.0,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25517672","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":"Commentary: Use of BACTRAC Proteomic Database-Uromodulin Protein Expression During Ischemic Stroke.","authors":"Gabriella-Salome K Armstrong,&nbsp;Jacqueline A Frank,&nbsp;Christopher J McLouth,&nbsp;Ann Stowe,&nbsp;Jill M Roberts,&nbsp;Amanda L Trout,&nbsp;Justin F Fraser,&nbsp;Keith Pennypacker","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Introduction: </strong>Uromodulin (UMOD) is a glycoprotein expressed by the epithelial cells of the thick ascending limb of Henle's loop in the kidney. Research has shown that increased uromodulin expression may be associated with lower risk of cardiovascular disease in adults. Utilizing the Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC) (clinicaltrials.gov NCT03153683), a continuously enrolling tissue bank, we aimed to examine the associations between serum uromodulin, age, and high BMI (BMI>25) and its relationship to stroke in patients.</p><p><strong>Methods: </strong>Arterial blood distal and proximal to the thrombus was collected during a thrombectomy procedure using the BACTRAC protocol and sent to Olink (Boston, MA) to determine proteomic expression via proximity extension assay. Uromodulin expression was recorded and analyzed using two tailed T-tests and linear regressions.</p><p><strong>Results: </strong>The relationship between systemic and intracranial uromodulin, age, high BMI and hypertension were assessed. Systemic and intracranial uromodulin decreased with age (p<0.0001 and r²=0.343, p=0.0416 and r²=0.102) respectively. Systemic uromodulin expression increased with BMI>25 (p=0.014). Presence of hypertension decreased uromodulin's expression systemically (p=0.018) and intracranially (p=0.007).</p><p><strong>Conclusions: </strong>Uromodulin was increased significantly in overweight patients, decreased significantly in older patients, and decreased in patients with hypertension. The increase in uromodulin in people with high BMI could be a protective reaction of the kidney to worsening conditions that make ischemic stroke more likely, with a goal of delaying dangerous outcomes. The decreased expression of uromodulin in older adults could be associated with the decline of general kidney function that accompanies aging. Hypertension can contribute to an AKI by decreasing perfusion to the kidney, therefore decreasing kidney function and uromodulin production. Further analyses are needed to understand the role of uromodulin following ischemic stroke.</p>","PeriodicalId":73744,"journal":{"name":"Journal of experimental neurology","volume":"2 1","pages":"29-33"},"PeriodicalIF":0.0,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9246699","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":"Commentary: Use of BACTRAC Proteomic Database-Uromodulin Protein Expression During Ischemic Stroke","authors":"Gabriella-Salome K. Armstrong, J. Frank, C. McLouth, A. Stowe, Jill M Roberts, A. Trout, J. Fraser, K. Pennypacker","doi":"10.33696/NEUROL.2.032","DOIUrl":"https://doi.org/10.33696/NEUROL.2.032","url":null,"abstract":"Introduction: Uromodulin (UMOD) is a glycoprotein expressed by the epithelial cells of the thick ascending limb of Henle’s loop in the kidney. Research has shown that increased uromodulin expression may be associated with lower risk of cardiovascular disease in adults. Utilizing the Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC) (clinicaltrials.gov NCT03153683), a continuously enrolling tissue bank, we aimed to examine the associations between serum uromodulin, age, and high BMI (BMI>25) and its relationship to stroke in patients. Methods: Arterial blood distal and proximal to the thrombus was collected during a thrombectomy procedure using the BACTRAC protocol and sent to Olink (Boston, MA) to determine proteomic expression via proximity extension assay. Uromodulin expression was recorded and analyzed using two tailed T-tests and linear regressions. Results: The relationship between systemic and intracranial uromodulin, age, high BMI and hypertension were assessed. Systemic and intracranial uromodulin decreased with age (p<0.0001 and r2=0.343, p=0.0416 and r2=0.102) respectively. Systemic uromodulin expression increased with BMI>25 (p=0.014). Presence of hypertension decreased uromodulin’s expression systemically (p=0.018) and intracranially (p=0.007). Conclusions: Uromodulin was increased significantly in overweight patients, decreased significantly in older patients, and decreased in patients with hypertension. The increase in uromodulin in people with high BMI could be a protective reaction of the kidney to worsening conditions that make ischemic stroke more likely, with a goal of delaying dangerous outcomes. The decreased expression of uromodulin in older adults could be associated with the decline of general kidney function that accompanies aging. Hypertension can contribute to an AKI by decreasing perfusion to the kidney, therefore decreasing kidney function and uromodulin production. Further analyses are needed to understand the role of uromodulin following ischemic stroke.","PeriodicalId":73744,"journal":{"name":"Journal of experimental neurology","volume":"2 1","pages":"29 - 33"},"PeriodicalIF":0.0,"publicationDate":"2021-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43263330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Commentary on Vulnerability and Resilience to Activity-Based Anorexia and the Role of Dopamine","authors":"J. Beeler, N. Burghardt","doi":"10.33696/NEUROL.2.031","DOIUrl":"https://doi.org/10.33696/NEUROL.2.031","url":null,"abstract":"Activity-based anorexia (ABA) is a commonly used rodent model of anorexia nervosa that is based on observations made in rats decades ago. In recently published work, we describe using this paradigm to model vulnerability and resilience to anorexia nervosa in mice, where vulnerability is characterized by hyperactivity and life-threatening weight loss and resilience is characterized by adaptation and weight stabilization. Using genetically modified hyperdopaminergic mice, we also demonstrate that increased dopamine augments vulnerability to ABA. Here, we briefly review our findings and discuss how obtaining vulnerable and resilient phenotypes enhances utility of the ABA model for understanding the neurobiological basis of anorexia nervosa. We comment on our dopamine findings and close by discussing implications for clinical treatment.","PeriodicalId":73744,"journal":{"name":"Journal of experimental neurology","volume":"2 1","pages":"21 - 28"},"PeriodicalIF":0.0,"publicationDate":"2021-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47848015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retroviral Elements in Human Evolution and Neural Development","authors":"Tongguang Wang, Tara T. Doucet-O’Hare, L. Henderson, Rachel P. M. Abrams, A. Nath","doi":"10.33696/NEUROL.2.028","DOIUrl":"https://doi.org/10.33696/NEUROL.2.028","url":null,"abstract":"Human embryogenesis and the development of its most unique product, the human brain, are believed to be precisely regulated by factors adopted during human evolution that differentiate us from other species. Nevertheless, increasing evidence shows an unthinkable “alien” factor may have contributed to the process. Pervasive horizontal gene transfer between species mediated by retroviruses is such a defining factor of evolution [1]. Retroviral infections occurred in germline cells and were able to transfer the genomic codes vertically from parent to offspring. These genes once integrated into the host chromosome, can get dispersed and exist in multiple mutated copies throughout the host genome. As a result, retroviral genes and other retro elements contribute to about 50% of the human genome. Of these, 20% belong to the group of LINEs and over 8% consists of HERVs which are relatively intact since they were acquired more recently [2]. From an evolutionary point of view, these retroviral elements have at least a few known functions that could benefit the human host. Generally, the vast amount of such “relic” genes in the genome can provide a specific buffer zone to preserve functional genes against further viral infections and other gene mutation causing events. The similarities of gene sequences and functions provide a more specific competition to limit further similar viral infections [3]. These functions are evidenced by the abnormal shares of mutations and translocations within the retroviral elements compared with other functional genes. Other functions of the HERV proteins lent to the host include the immune regulatory functions, such as an immunosuppressive function mediated by a domain located in the transmembrane subunit of the HERV-W [4,5]. In the present review, we focus on the effects of retroviral elements on human embryogenesis and neural development.","PeriodicalId":73744,"journal":{"name":"Journal of experimental neurology","volume":"2 1","pages":"1 - 9"},"PeriodicalIF":0.0,"publicationDate":"2021-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44820069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cathepsin D: A Candidate Link between Amyloid β-protein and Tauopathy in Alzheimer Disease","authors":"Caitlin N Suire, M. Leissring","doi":"10.33696/NEUROL.2.029","DOIUrl":"https://doi.org/10.33696/NEUROL.2.029","url":null,"abstract":"Alzheimer disease (AD) is a debilitating neurodegenerative disorder characterized by extracellular deposition of the amyloid β-protein (Aβ) and intraneuronal accumulation of the microtubule-associated protein, tau. Despite a wealth of experimental and genetic evidence implicating both Aβ and tau in the pathogenesis of AD, the precise molecular links between these two pathological hallmarks have remained surprisingly elusive. Here, we review emerging evidence for a critical nexus among Aβ, tau, and the lysosomal protease cathepsin D (CatD) that we hypothesize may play a pivotal role in the etiology of AD. CatD degrades both Aβ and tau in vitro, but the in vivo relevance of this lysosomal protease to these principally extracellular and cytosolic proteins, respectively, had remained undefined for many decades. Recently, however, our group found that genetic deletion of CatD in mice results in dramatic accumulation of Aβ in lysosomes, revealing that Aβ is normally trafficked to lysosomes in substantial quantities. Moreover, emerging evidence suggests that tau is also trafficked to the lysosome via chaperone-mediated autophagy and other trafficking pathways. Thus, Aβ, tau and CatD are colocalized in the lysosome, an organelle that shows dysfunction early in AD pathogenesis, where they can potentially interact. Notably, we discovered that Aβ42—the Aβ species most strongly linked to AD pathogenesis—is a highly potent, low-nanomolar, competitive inhibitor of CatD. Taking these observations together, we hypothesize that Aβ42 may trigger tauopathy by competitive inhibition of CatD-mediated degradation of tau—pathogenic forms of tau, in particular. Herein, we review the evidence supporting this hypothesis and explore the implications for the molecular pathogenesis of AD. Future research into these novel mechanistic links among Aβ, tau and CatD promises to expand our understanding of the etiology of AD and could potentially lead to novel therapeutic approaches for combatting this devastating disease of brain and mind.","PeriodicalId":73744,"journal":{"name":"Journal of experimental neurology","volume":"2 1","pages":"10 - 15"},"PeriodicalIF":0.0,"publicationDate":"2021-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42641129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}