Journal of Experimental Neuroscience最新文献

{"title":"Thanks to reviewers-2018","authors":"Julia, Cardinali","doi":"10.1177/1179069519829632","DOIUrl":"https://doi.org/10.1177/1179069519829632","url":null,"abstract":"Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). Journal of Experimental Neuroscience Volume 13: 1 © The Author(s) 2019 Article reuse guidelines: sagepub.com/journals-permissions DOI: 10.1177/1 79069519829632","PeriodicalId":15817,"journal":{"name":"Journal of Experimental Neuroscience","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179069519829632","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45990036","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":"ZPR1-Dependent Neurodegeneration Is Mediated by the JNK Signaling Pathway","authors":"Xiaoting Jiang, Annapoorna Kannan, L. Gangwani","doi":"10.1177/1179069519867915","DOIUrl":"https://doi.org/10.1177/1179069519867915","url":null,"abstract":"The zinc finger protein ZPR1 deficiency causes neurodegeneration and results in a mild spinal muscular atrophy (SMA)-like disease in mice with reduced Zpr1 gene dosage. Mutation of the survival motor neuron 1 (SMN1) gene causes SMA. Spinal muscular atrophy is characterized by the degeneration of the spinal cord motor neurons caused by chronic low levels of SMN protein. ZPR1 interacts with SMN and is required for nuclear accumulation of SMN. Patients with SMA express reduced levels of ZPR1. Reduced Zpr1 gene dosage increases neurodegeneration and severity of SMA disease in mice. Mechanisms underlying ZPR1-dependent neurodegeneration are largely unknown. We report that neurodegeneration caused by ZPR1 deficiency is mediated by the c-Jun NH2-terminal kinase (JNK) group of mitogen-activated protein kinases (MAPK). ZPR1-dependent neuron degeneration is mediated by central nervous system (CNS)-specific isoform JNK3. ZPR1 deficiency activates the MAPK signaling cascade, MLK3 → MKK7 → JNK3, which phosphorylates c-Jun and activates caspase-mediated neuron degeneration. Neurons from Jnk3-null mice show resistance to ZPR1-dependent neurodegeneration. Pharmacologic inhibition of JNK reduces degeneration of ZPR1-deficient neurons. These data show that ZPR1-dependent neurodegeneration is mediated by the JNK signaling pathway and suggest that ZPR1 downregulation in SMA may contribute to JNK-mediated neurodegeneration associated with SMA pathogenesis.","PeriodicalId":15817,"journal":{"name":"Journal of Experimental Neuroscience","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179069519867915","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44369965","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":"Why Is Mom Stressed: Homeorhesis as the Potential Problem and Nicotinamide Riboside as the Potential Solution","authors":"C. Brenner","doi":"10.1177/1179069519869679","DOIUrl":"https://doi.org/10.1177/1179069519869679","url":null,"abstract":"The remodeling of female mammalian physiology to support the development of a fertilized egg into an externally breathing individual and then to provide all the nutrition to this individual while remodeling back to nearly her pregestational state is without parallel in male mammalian physiological transitions. While it is common parlance to refer to postpartum depression as a not infrequent stress in women, the postpartum physiological changes after every birth constitute profound metabolic stresses that are understudied and have important nutritional, behavioral, and neurodevelopmental implications for the maternal and neonatal health of every mammalian species. We discovered that the postpartum liver of a lactating female mouse has a depressed nicotinamide adenine dinucleotide (NAD) metabolome linked to circulation of higher levels of NAD metabolites in support of a >20-fold increase in NAD coenzymes in the mammary. Furthermore, by supporting a new mother’s apparent higher demand for NAD precursors, we increased circulation of prolactin, superinduced mammary biosynthetic programs, increased her time of arched-back nursing, enhanced mammary production of brain-derived neurotrophic factor, promoted postgestational weight loss, advanced the neurobehavioral development of her offspring, and allowed them to mature as stronger and more resilient adults with advantages in hippocampal neurogenesis and body composition. These results show that a new mother’s capacity for biosynthesis and functionally important nurturing is apparently limited by NAD. Here, we discuss homeorhetic flow of resources from a new mother to her offspring in the context of NAD metabolism and suggest avenues for future investigation.","PeriodicalId":15817,"journal":{"name":"Journal of Experimental Neuroscience","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179069519869679","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41955907","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":"Obesity Impairs Mobility and Adult Hippocampal Neurogenesis","authors":"A. Bracke, G. Domańska, K. Bracke, S. Harzsch, J. van den Brandt, B. Bröker, O. von Bohlen und Halbach","doi":"10.1177/1179069519883580","DOIUrl":"https://doi.org/10.1177/1179069519883580","url":null,"abstract":"Currently, it is controversially discussed whether a relationship between obesity and cognition exists. We here analyzed a mouse model of obesity (leptin-deficient mice) to study the effects of obesity on the morphology of the hippocampus (a brain structure involved in mechanisms related to learning and memory) and on behavior. Mice aged 4 to 6 months were analyzed. At this age, the obese mice have nearly double the body weight as controls, but display smaller brains (brain volume is about 10% smaller) as control animals of the same age. Adult hippocampal neurogenesis, a process that is linked to learning and memory, might be disturbed in the obese mice and contribute to the smaller brain volume. Adult hippocampal neurogenesis was examined using specific markers for cell proliferation (phosphohistone H3), neuronal differentiation (doublecortin), and apoptosis (caspase 3). The number of phosphohistone H3 and doublecortin-positive cells was markedly reduced in leptin-deficient mice, but not the number of apoptotic cells, indicating that adult hippocampal neurogenesis on the level of cell proliferation was affected. In addition, dendritic spine densities of pyramidal neurons in the hippocampal area CA1 were analyzed using Golgi impregnation. However, no significant change in dendritic spine densities was noted in the obese mice. Moreover, the performance of the mice was analyzed in the open field as well as in the Morris water maze. In the open field test, obese mice showed reduced locomotor activity, but in the Morris water maze they showed similar performance compared with control animals.","PeriodicalId":15817,"journal":{"name":"Journal of Experimental Neuroscience","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179069519883580","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43962001","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":"Diffusion Tensor Imaging of the Evolving Response to Mild Traumatic Brain Injury in Rats","authors":"W. S. Hoogenboom, Todd G Rubin, Kenny Q. Ye, Min-Hui Cui, Kelsey C Branch, Jinyuan Liu, C. Branch, M. Lipton","doi":"10.1177/1179069519858627","DOIUrl":"https://doi.org/10.1177/1179069519858627","url":null,"abstract":"Mild traumatic brain injury (mTBI), also known as concussion, is a serious public health challenge. Although most patients recover, a substantial minority suffers chronic disability. The mechanisms underlying mTBI-related detrimental effects remain poorly understood. Although animal models contribute valuable preclinical information and improve our understanding of the underlying mechanisms following mTBI, only few studies have used diffusion tensor imaging (DTI) to study the evolution of axonal injury following mTBI in rodents. It is known that DTI shows changes after human concussion and the role of delineating imaging findings in animals is therefore to facilitate understanding of related mechanisms. In this work, we used a rodent model of mTBI to investigate longitudinal indices of axonal injury. We present the results of 45 animals that received magnetic resonance imaging (MRI) at multiple time points over a 2-week period following concussive or sham injury yielding 109 serial observations. Overall, the evolution of DTI metrics following concussive or sham injury differed by group. Diffusion tensor imaging changes within the white matter were most noticeable 1 week following injury and returned to baseline values after 2 weeks. More specifically, we observed increased fractional anisotropy in combination with decreased radial diffusivity and mean diffusivity, in the absence of changes in axial diffusivity, within the white matter of the genu corpus callosum at 1 week post-injury. Our study shows that DTI can detect microstructural white matter changes in the absence of gross abnormalities as indicated by visual screening of anatomical MRI and hematoxylin and eosin (H&E)-stained sections in a clinically relevant animal model of mTBI. Whereas additional histopathologic characterization is required to better understand the neurobiological correlates of DTI measures, our findings highlight the evolving nature of the brain’s response to injury following concussion.","PeriodicalId":15817,"journal":{"name":"Journal of Experimental Neuroscience","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179069519858627","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44467341","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":"Suppression of MAP4K4 Signaling Ameliorates Motor Neuron Degeneration in Amyotrophic Lateral Sclerosis-Molecular Studies Toward New Therapeutics","authors":"M. Watts, Chen Wu, L. Rubin","doi":"10.1177/1179069519862798","DOIUrl":"https://doi.org/10.1177/1179069519862798","url":null,"abstract":"Amyotrophic lateral sclerosis (ALS), the most common motor neuron (MN) disease of adults, is characterized by the degeneration of upper MNs in the motor cortex and lower MNs in the brain stem and spinal cord. Our recent work suggests that a MAP kinase family member, MAP4K4 (mitogen-activated protein kinase kinase kinase kinase 4), regulates MN degeneration in ALS. Activation of MAP4K4 occurs prior to MN death and inhibition of MAP4K4 improves neurite integrity and neuronal viability in a cell autonomous manner. The mechanism through which MAP4K4 reduction specifically modulates MN viability can be attributed to the attenuation of the c-Jun apoptotic pathway, as well as to the activation of FoxO1-mediated autophagy that reduces the accumulation of protein aggregates. We additionally show the feasibility of MAP4K4 as a drug target using a MAP4K4-specific inhibitor, which improves the survival of both primary and induced pluripotent stem cell (iPSC)-derived MNs. Our studies are thus far the first to highlight a MAP4K4-initiated signaling cascade that contributes to MN degeneration in ALS, providing a new mechanism underlying MN death in disease and a druggable target for new therapeutics. We propose exciting future directions and unexplored avenues based upon this work.","PeriodicalId":15817,"journal":{"name":"Journal of Experimental Neuroscience","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179069519862798","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42763649","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":"Neurological Disease Modelling for Spinocerebellar Ataxia Using Zebrafish","authors":"K. Namikawa, A. Dorigo, R. Köster","doi":"10.1177/1179069519880515","DOIUrl":"https://doi.org/10.1177/1179069519880515","url":null,"abstract":"The cerebellum integrates sensory information and motor actions. Increasing experimental evidence has revealed that these functions as well as the cerebellar cytoarchitecture are highly conserved in zebrafish compared with mammals. However, the potential of zebrafish for modelling human cerebellar diseases remains to be addressed. Spinocerebellar ataxias (SCAs) represent a group of genetically inherited cerebellar diseases leading to motor discoordination that is most often caused by affected cerebellar Purkinje cells (PCs). Towards modelling SCAs in zebrafish we identified a small-sized PC-specific regulatory element that was used to develop coexpression vectors with tunable expression strength. These vectors allow for in vivo imaging of SCA-affected PCs by high-resolution fluorescence imaging. Next, zebrafish with SCA type 13 (SCA13) transgene expression were established, revealing that SCA13-induced cell-autonomous PC degeneration results in eye movement deficits. Thus, SCA13 zebrafish mimic the neuropathology of an SCA-affected brain as well as the involved loss of motor control and hence provide a powerful approach to unravel SCA13-induced cell biological pathogenic and cytotoxic mechanisms.","PeriodicalId":15817,"journal":{"name":"Journal of Experimental Neuroscience","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179069519880515","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47913305","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":"A Further Analysis and Commentary on: Profiling Changes in Cortical Astroglial Cells Following Chronic Stress","authors":"Gianfilippo Coppola, G. Rurak, Stephanie Simard, N. Salmaso","doi":"10.1177/1179069519870182","DOIUrl":"https://doi.org/10.1177/1179069519870182","url":null,"abstract":"The neuroplasticity hypothesis of depression proposes that major depressive disorders are related to decreased hippocampal and cortical neural plasticity, which is reversed by antidepressant treatment. Astroglial cells have emerged as key mediators of neural plasticity and are involved in the cause and treatment of depression and anxiety-like behaviors. One of the ways that astroglia modulate neuroplasticity is through the formation and maintenance of perineuronal nets (PNNs). Perineuronal nets are important extracellular matrix components that respond to stress and are implicated in anxiety-like behaviors. Normally, astroglial cells continuously turnover PNNs by degrading and donating PNN proteins; however, chronic stress slows PNN protein degradation and increases cortical PNN expression overall. In this report, we used weighted gene co-expression network analysis and eigengene analysis to further delineate the pathways and key regulators involved in the astroglial-PNN relationship following chronic stress. Our analyses indicate that chronic variable stress induces the expression of PNNs through inhibition of trophic pathways and key transcription factors in astroglial cells. These data further support the integral role of astroglial cells in the neuroplasticity hypothesis of depression through their modulation of anxiety-like behaviors and PNNs.","PeriodicalId":15817,"journal":{"name":"Journal of Experimental Neuroscience","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179069519870182","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46149925","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":"Assessment of Improvement in Oxidative Stress Indices with Resocialization in Memory Retrieval in Y-Maze in Male Rats.","authors":"Hamidreza Famitafreshi,&nbsp;Morteza Karimian","doi":"10.1177/1179069518820323","DOIUrl":"https://doi.org/10.1177/1179069518820323","url":null,"abstract":"<p><strong>Introduction: </strong>Memory deficit is an important issue in some psychiatric diseases either as a primary symptom or as a comorbid symptom. Factors that determine the decline or improvement of memory are an important subject to reduce the severity of these diseases.</p><p><strong>Methods and materials: </strong>In this study, 32 male Sprague-Dawley rats were randomly divided into 4 experimental groups: social (control), isolation, resocialization for 3 days, and resocialization for 7 days. Isolation occurred for 14 days. Resocialization groups were resocialized for 3 or 7 days after isolation. In the social group, there was no intervention with normal socializing among the rats. In the isolation group, rats were isolated with no resocialization. In all 4 groups, after performing the Y-maze, the rats' brains were removed to assess oxidative stress status in the hippocampus and prefrontal cortex.</p><p><strong>Results: </strong>Y-maze performance improved after 3 and 7 days of resocialization. However, oxidative stress status for malondialdehyde, glutathione and nitrite/nitrate returned to normal levels except in 2 experiments after 7 days of resocialization. In addition, in 2 experiments, just glutathione in the prefrontal cortex and nitrite/nitrate in the hippocampus after 3 days of resocialization improved.</p><p><strong>Conclusions: </strong>A return to normal levels in all types of antioxidant markers in the resocialization groups is not the only factor for improving memory deficits resulting from isolation. Resocialization may also be activating other regulatory mechanisms besides an antioxidant defense.</p>","PeriodicalId":15817,"journal":{"name":"Journal of Experimental Neuroscience","volume":"12 ","pages":"1179069518820323"},"PeriodicalIF":0.0,"publicationDate":"2018-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179069518820323","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36838857","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":"An Overlooked Brain Region in the Aetiology of Anorexia Nervosa: The Importance of Behaviourally Driven Neuroimaging Analysis.","authors":"Andrea Phillipou,&nbsp;David Jonathan Castle,&nbsp;Larry Allen Abel,&nbsp;Caroline Gurvich,&nbsp;Susan Lee Rossell","doi":"10.1177/1179069518820068","DOIUrl":"https://doi.org/10.1177/1179069518820068","url":null,"abstract":"<p><p>The neurobiological contributions to anorexia nervosa (AN) remain poorly understood, hindering the development of effective neurobiological treatments such as medications and brain stimulation. A large number of studies have been undertaken utilising neuroimaging techniques, such as magnetic resonance imaging (MRI), to gain a better understanding of the brain mechanisms involved in the illness. However, the analyses undertaken by many studies have utilised a whole-brain analytical approach as much of this research has been exploratory in nature. This is, however, problematic as small brain regions that differ between groups may not have the statistical power to produce statistically significant results. This is highlighted in a recent study undertaken by our group utilising diffusion-weighted imaging. In this research, we identified widespread white matter microstructural differences in individuals with AN, but only showed differences in a small brain region (the superior colliculus) when a region-of-interest approach that was driven by behavioural findings was utilised. The importance of hypothesis-driven neuroimaging analyses is discussed in this article.</p>","PeriodicalId":15817,"journal":{"name":"Journal of Experimental Neuroscience","volume":"12 ","pages":"1179069518820068"},"PeriodicalIF":0.0,"publicationDate":"2018-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179069518820068","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36838855","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}