Molecular and Cellular Neuroscience最新文献

{"title":"Glycogen phosphorylase isoenzyme GPbb versus GPmm regulation of ventromedial hypothalamic nucleus glucoregulatory neurotransmitter and counter-regulatory hormone profiles during hypoglycemia: Role of L-lactate and octadecaneuropeptide","authors":"Md. Main Uddin ,&nbsp;Md. Haider Ali ,&nbsp;A.S.M.H. Mahmood ,&nbsp;Khaggeswar Bheemanapally ,&nbsp;Jérôme Leprince ,&nbsp;Karen P. Briski","doi":"10.1016/j.mcn.2023.103863","DOIUrl":"10.1016/j.mcn.2023.103863","url":null,"abstract":"<div><p><span><span>Glucose accesses the brain primarily via the astrocyte cell compartment, where it passes through the glycogen shunt before catabolism to the oxidizable fuel L-lactate. Glycogen phosphorylase (GP) </span>isoenzymes<span><span> GPbb and GPmm impose distinctive control of ventromedial hypothalamic nucleus (VMN) glucose-regulatory neurotransmission during hypoglycemia, but lactate and/or </span>gliotransmitter<span><span> involvement in those actions is unknown. Lactate or the octadecaneuropeptide </span>receptor antagonist cyclo(1–8)[DLeu</span></span></span>⁵<span><span>] OP (LV-1075) did not affect gene product down-regulation caused by GPbb or GPmm siRNA<span>, but suppressed non-targeted GP variant expression in a VMN region-specific manner. Hypoglycemic up-regulation of neuronal nitric oxide synthase was enhanced in rostral and caudal VMN by GPbb knockdown, yet attenuated by GPMM siRNA in the middle VMN; lactate or LV-1075 reversed these silencing effects. Hypoglycemic inhibition of </span></span>glutamate decarboxylase65/67 was magnified by GPbb (middle and caudal VMN) or GPmm (middle VMN) knockdown, responses that were negated by lactate or LV-1075. GPbb or GPmm siRNA enlarged hypoglycemic VMN glycogen profiles in rostral and middle VMN. Lactate and LV-1075 elicited progressive rostral VMN glycogen augmentation in GPbb knockdown rats, but stepwise-diminution of rostral and middle VMN glycogen after GPmm silencing. GPbb, not GPmm, knockdown caused lactate or LV-1075 – reversible amplification of hypoglycemic hyperglucagonemia and hypercorticosteronemia. Results show that lactate and octadecaneuropeptide exert opposing control of GPbb protein in distinct VMN regions, while the latter stimulates GPmm. During hypoglycemia, GPbb and GPmm may respectively diminish (rostral, caudal VMN) or enhance (middle VMN) nitrergic transmission and each oppose GABAergic signaling (middle VMN) by lactate- and octadecaneuropeptide-dependent mechanisms.</span></p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"126 ","pages":"Article 103863"},"PeriodicalIF":3.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10527669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10156655","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":"Paternal morphine exposure in rats reduces social play in adolescent male progeny without affecting drug-taking behavior in juvenile males or female offspring","authors":"Dana Zeid ,&nbsp;Andre B. Toussaint ,&nbsp;Carmen C. Dressler ,&nbsp;Samuel P. Schumacher ,&nbsp;Chau Do ,&nbsp;Heather Desalvo ,&nbsp;Danait Selamawi ,&nbsp;Angela R. Bongiovanni ,&nbsp;Hannah L. Mayberry ,&nbsp;Gregory V. Carr ,&nbsp;Mathieu E. Wimmer","doi":"10.1016/j.mcn.2023.103877","DOIUrl":"10.1016/j.mcn.2023.103877","url":null,"abstract":"<div><p><span><span>The ongoing opioid addiction<span> crisis necessitates the identification of novel risk factors to improve prevention and treatment of opioid use disorder. Parental opioid exposure has recently emerged as a potential regulator of offspring vulnerability to opioid misuse, in addition to heritable genetic liability. An understudied aspect of this “missing heritability” is the developmental presentation of these cross-generational phenotypes. This is an especially relevant question in the context of inherited addiction-related phenotypes, given the prominent role of developmental processes in the etiology of psychiatric disorders. Paternal morphine self-administration was previously shown to alter the sensitivity to the reinforcing and antinociceptive properties of opioids in the next generation. Here, phenotyping was expanded to include the adolescent period, with a focus on </span></span>endophenotypes related to opioid use disorders and pain. Paternal morphine exposure did not alter heroin or cocaine self-administration in male and female juvenile progeny. Further, baseline sensory reflexes related to pain were unaltered in morphine-sired adolescent rats of either sex. However, morphine-sired adolescent males exhibited a reduction in social play </span>behavior. Our findings suggest that, in morphine-sired male offspring, paternal opioid exposure does not affect opioid intake during adolescence, suggesting that this phenotype does not emerge until later in life. Altered social behaviors in male morphine-sired adolescents indicate that the changes in drug-taking behavior in adults sired by morphine-exposed sires may be due to more complex factors not yet fully assessed.</p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"126 ","pages":"Article 103877"},"PeriodicalIF":3.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10528482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10165768","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":"The intracellular C-terminal domain of mGluR6 contains ER retention motifs","authors":"Atsushi Shimohata ,&nbsp;Dilip Rai ,&nbsp;Takumi Akagi,&nbsp;Sumiko Usui,&nbsp;Ikuo Ogiwara,&nbsp;Makoto Kaneda","doi":"10.1016/j.mcn.2023.103875","DOIUrl":"10.1016/j.mcn.2023.103875","url":null,"abstract":"<div><p>Metabotropic glutamate<span><span> receptor 6 (mGluR6) predominantly localizes to the postsynaptic sites of retinal ON-bipolar cells, at which it recognizes glutamate released from photoreceptors<span><span><span>. The C-terminal domain (CTD) of mGluR6 contains a cluster of basic amino acids resembling motifs for </span>endoplasmic reticulum<span> (ER) retention. We herein investigated whether these basic residues are involved in regulating the subcellular localization of mGluR6 in 293T cells expressing mGluR6 CTD mutants using </span></span>immunocytochemistry<span>, immunoprecipitation, and flow cytometry. We showed that full-length mGluR6 localized to the ER and cell surface, whereas mGluR6 mutants with 15- and 20-amino acid deletions from the C terminus localized to the ER, but were deficient at the cell surface. We also demonstrated that the cell surface deficiency of mGluR6 mutants was rescued by introducing an </span></span></span>alanine<span> substitution at basic residues within the CTD. The surface-deficient mGluR6 mutant still did not localize to the cell surface and was retained in the ER when co-expressed with surface-expressible constructs, including full-length mGluR6, even though surface-deficient and surface-expressible constructs formed heteromeric complexes. The co-expression of the surface-deficient mGluR6 mutant reduced the surface levels of surface-expressible constructs. These results indicate that basic residues in the mGluR6 CTD served as ER retention signals. We suggest that exposed ER retention motifs in the aberrant assembly containing truncated or misfolded mGluR6 prevent these protein complexes from being transported to the cell surface.</span></span></p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"126 ","pages":"Article 103875"},"PeriodicalIF":3.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10168541","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":"Endogenous epitope tagging of eEF1A2 in mice reveals early embryonic expression of eEF1A2 and subcellular compartmentalisation of neuronal eEF1A1 and eEF1A2","authors":"Faith C.J. Davies ,&nbsp;Grant F. Marshall ,&nbsp;Eleanor Pegram ,&nbsp;Danni Gadd ,&nbsp;Catherine M. Abbott","doi":"10.1016/j.mcn.2023.103879","DOIUrl":"10.1016/j.mcn.2023.103879","url":null,"abstract":"<div><p>All vertebrate species express two independently-encoded forms of translation elongation factor eEF1A. In humans and mice eEF1A1 and eEF1A2 are 92 % identical at the amino acid level, but the well conserved developmental switch between the two variants in specific tissues suggests the existence of important functional differences. Heterozygous mutations in eEF1A2 result in neurodevelopmental disorders in humans; the mechanism of pathogenicity is unclear, but one hypothesis is that there is a dominant negative effect on eEF1A1 during development. The high degree of similarity between the eEF1A proteins has complicated expression analysis in the past; here we describe a gene edited mouse line in which we have introduced a V5 tag in the gene encoding eEF1A2. Expression analysis using anti-V5 and anti-eEF1A1 antibodies demonstrates that, in contrast to the prevailing view that eEF1A2 is only expressed postnatally, it is expressed from as early as E11.5 in the developing neural tube. Two colour immunofluorescence also reveals coordinated switching between eEF1A1 and eEF1A2 in different regions of postnatal brain. Completely reciprocal expression of the two variants is seen in post-weaning mouse brain with eEF1A1 expressed in oligodendrocytes and astrocytes and eEF1A2 in neuronal soma. Although eEF1A1 is absent from neuronal cell bodies after development, it is widely expressed in axons. This expression does not appear to coincide with myelin sheaths originating from oligodendrocytes but rather results from localised translation within the axon, suggesting that both variants are transcribed in neurons but show completely distinct subcellular localisation at the protein level. These findings will form an underlying framework for understanding how missense mutations in eEF1A2 result in neurodevelopmental disorders.</p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"126 ","pages":"Article 103879"},"PeriodicalIF":3.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10168577","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":"Expanded polyQ aggregates interact with sarco-endoplasmic reticulum calcium ATPase and Drosophila inhibitor of apoptosis protein1 to regulate polyQ mediated neurodegeneration in Drosophila","authors":"Chandan Kumar Maurya,&nbsp;Madhu G. Tapadia","doi":"10.1016/j.mcn.2023.103886","DOIUrl":"10.1016/j.mcn.2023.103886","url":null,"abstract":"<div><p><span>Polyglutamine (polyQ) induced neurodegeneration<span> is one of the leading causes of progressive neurodegenerative disorders characterized clinically by deteriorating movement defects, psychiatric disability, and dementia. Calcium [Ca</span></span>²⁺<span><span>] homeostasis, which is essential for the functioning of neuronal cells, is disrupted under these pathological conditions. In this paper, we simulated </span>Huntington's disease phenotype in the neuronal cells of the </span><em>Drosophila</em> eye and identified [Ca²⁺<span><span>] pump, sarco-endoplasmic reticulum calcium ATPase (SERCA), as one of the </span>genetic<span> modifiers of the neurodegenerative phenotype. This paper shows genetic and molecular interaction between polyglutamine (polyQ) aggregates, SERCA and DIAP1. We present evidence that polyQ aggregates interact with SERCA and alter its dynamics, resulting in a decrease in cytosolic [Ca</span></span>²⁺] and an increase in ER [Ca²⁺<span>], and thus toxicity. Downregulating SERCA lowers the enhanced calcium levels in the ER and rescues, morphological and functional defects caused due to expanded polyQ repeats. Cell proliferation markers such as Yorkie (Yki), Scalloped (Sd), and phosphatidylinositol 3 kinases/protein kinase B (PI3K/Akt), also respond to varying levels of calcium due to genetic manipulations, adding to the amelioration of degeneration. These results imply that neurodegeneration due to expanded polyQ repeats is sensitive to SERCA activity, and its manipulation can be an important step toward its therapeutic measures.</span></p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"126 ","pages":"Article 103886"},"PeriodicalIF":3.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10223627","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":"A novel anti-apoptotic role for Cdc42/ACK-1 signaling in neurons","authors":"Noelle C. Punessen ,&nbsp;Claudia Pena ,&nbsp;Alexandra Sandberg ,&nbsp;Lilia A. Koza ,&nbsp;Daniel A. Linseman","doi":"10.1016/j.mcn.2023.103865","DOIUrl":"10.1016/j.mcn.2023.103865","url":null,"abstract":"<div><p>Neurodegenerative diseases such as amyotrophic lateral sclerosis, Alzheimer's and Parkinson's disease are caused by a progressive and aberrant destruction of neurons in the brain and spinal cord. These disorders lack effective long-term treatments that impact the underlying mechanisms of pathogenesis and as a result, existing options focus primarily on alleviating symptomology. Dysregulated programmed cell death (i.e., apoptosis) is a significant contributor to neurodegeneration, and is controlled by a number of different factors. Rho family GTPases are molecular switches with recognized importance in proper neuronal development and migration that have more recently emerged as central regulators of apoptosis and neuronal survival. Here, we investigated a role for the Rho GTPase family member, Cdc42, and its downstream effectors, in neuronal survival and apoptosis. We initially induced apoptosis in primary cultures of rat cerebellar granule neurons (CGNs) by removing both growth factor-containing serum and depolarizing potassium from the cell medium. We then utilized both chemical inhibitors and adenoviral shRNA targeted to Cdc42 to block the function of Cdc42 or its downstream effectors under either control or apoptotic conditions. Our in vitro studies demonstrate that functional inhibition of Cdc42 or its downstream effector, activated Cdc42-associated tyrosine kinase-1 (ACK-1), had no adverse effects on CGN survival under control conditions, but significantly sensitized neurons to cell death under apoptotic conditions. In conclusion, our results suggest a key pro-survival role for Cdc42/ACK-1 signaling in neurons, particularly in regulating neuronal susceptibility to pro-apoptotic stress such as that observed in neurodegenerative disorders.</p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"126 ","pages":"Article 103865"},"PeriodicalIF":3.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10156650","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":"Glutamine metabolism in diseases associated with mitochondrial dysfunction","authors":"Rebecca Bornstein ,&nbsp;Michael T. Mulholland ,&nbsp;Margaret Sedensky ,&nbsp;Phil Morgan ,&nbsp;Simon C. Johnson","doi":"10.1016/j.mcn.2023.103887","DOIUrl":"10.1016/j.mcn.2023.103887","url":null,"abstract":"<div><p>Mitochondrial dysfunction can arise from genetic defects or environmental exposures and impact a wide range of biological processes. Among these are metabolic pathways involved in glutamine catabolism, anabolism, and glutamine-glutamate cycling. In recent years, altered glutamine metabolism has been found to play important roles in the pathologic consequences of mitochondrial dysfunction. Glutamine is a pleiotropic molecule, not only providing an alternate carbon source to glucose in certain conditions, but also playing unique roles in cellular communication in neurons and astrocytes. Glutamine consumption and catabolic flux can be significantly altered in settings of genetic mitochondrial defects or exposure to mitochondrial toxins, and alterations to glutamine metabolism appears to play a particularly significant role in neurodegenerative diseases. These include primary mitochondrial diseases like Leigh syndrome (subacute necrotizing encephalopathy) and MELAS (mitochondrial myopathy with encephalopathy, lactic acidosis, and stroke-like episodes), as well as complex age-related neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Pharmacologic interventions targeting glutamine metabolizing and catabolizing pathways appear to provide some benefits in cell and animal models of these diseases, indicating glutamine metabolism may be a clinically relevant target. In this review, we discuss glutamine metabolism, mitochondrial disease, the impact of mitochondrial dysfunction on glutamine metabolic processes, glutamine in neurodegeneration, and candidate targets for therapeutic intervention.</p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"126 ","pages":"Article 103887"},"PeriodicalIF":3.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10164885","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":"Effect of germ-free status on transcriptional profiles in the nucleus accumbens and transcriptomic response to chronic morphine","authors":"Jonathon P. Sens ,&nbsp;Rebecca S. Hofford ,&nbsp;Drew D. Kiraly","doi":"10.1016/j.mcn.2023.103874","DOIUrl":"10.1016/j.mcn.2023.103874","url":null,"abstract":"<div><p><span><span><span>Opioid use disorder is a public health crisis that causes tremendous suffering for patients as well as substantial social and economic costs for society. There are currently available treatments for patients with opioid use disorder, but they remain intolerable or ineffective for many. Thus the need to develop new avenues for therapeutics development in this space is great. Substantial work in models of substance use disorders, including opioid use disorder, demonstrates that prolonged exposure to drugs of abuse leads to marked transcriptional and epigenetic dysregulation in limbic substructures. It is widely believed that these changes in gene regulation in response to drugs are a key driving factor in the perpetuation of drug taking and seeking </span>behaviors. Thus, development of interventions that could shape transcriptional regulation in response to drugs of abuse would be of high value. Over the past decade there has been a surge in research demonstrating that the resident bacteria of the </span>gastrointestinal tract<span>, collectively the gut microbiome, can have tremendous influence on neurobiological and behavioral plasticity. Previous work from our group and others has demonstrated that alterations in the gut microbiome can alter behavioral responses to opioids in multiple paradigms. Additionally, we have previously reported that depletion of the gut microbiome with antibiotics markedly shifts the </span></span>transcriptome<span> of the nucleus accumbens<span> following prolonged morphine exposure. In this manuscript we present a comprehensive analysis of the effects of the gut microbiome on transcriptional regulation of the nucleus accumbens following morphine by utilizing germ-free, antibiotic treated, and control mice. This allows for detailed understanding of the role of the microbiome in regulating baseline transcriptomic control, as well as response to morphine. We find that germ-free status leads to a marked gene dysregulation in a manner distinct to adult mice treated with antibiotics, and that altered gene pathways are highly related to cellular metabolic processes. These data provide additional insight into the role of the gut microbiome in modulating brain function and lay a foundation for further study in this area.</span></span></p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"126 ","pages":"Article 103874"},"PeriodicalIF":3.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10166564","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":"Profiling transcriptomic responses of human stem cell-derived medium spiny neuron-like cells to exogenous phasic and tonic neurotransmitters","authors":"Ryan W Tam PhD,&nbsp;Albert J. Keung","doi":"10.1016/j.mcn.2023.103876","DOIUrl":"10.1016/j.mcn.2023.103876","url":null,"abstract":"<div><p><span><span><span>Transcriptomic<span> responses to neurotransmitters contribute to the complex processes driving memory and addiction. Advances in both measurement methods and experimental models continue to improve our understanding of this regulatory layer. Here we focus on the experimental potential of stem cell derived neurons, currently the only ethical model that can be used in reductionist and experimentally perturbable studies of human cells. Prior work has focused on generating distinct cell types from human stem cells, and has also shown their utility in modeling development and cellular phenotypes related to </span></span>neurodegeneration<span>. Here we seek an understanding of how stem cell derived neural cultures respond to perturbations experienced during development and disease progression. This work profiles transcriptomic responses of human medium spiny neuron-like cells with three specific goals. We first characterize transcriptomic responses to dopamine and dopamine receptor agonists and antagonists presented in dosing patterns mimicking acute, chronic, and withdrawal regimens. We also assess transcriptomic responses to low and persistent tonic levels of dopamine, </span></span>acetylcholine, and </span>glutamate to better mimic the in vivo environment. Finally, we identify similar and distinct responses between hMSN-like cells derived from H9 and H1 stem cell lines, providing some context for the extent of variability these types of systems will likely pose for experimentalists. The results here suggest future optimizations of human stem cell derived neurons to increase their in vivo relevance and the biological insights that can be garnered from these models.</p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"126 ","pages":"Article 103876"},"PeriodicalIF":3.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10528483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10157127","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":"Recovery of motor function is associated with rescue of glutamate biomarkers in the striatum and motor cortex following treatment with Mucuna pruriens in a murine model of Parkinsons disease","authors":"Tanya Denne ,&nbsp;Lila C. Winfrey ,&nbsp;Cindy Moore ,&nbsp;Chase Whitner ,&nbsp;Theresa D'Silva ,&nbsp;Amala Soumyanath ,&nbsp;Lynne Shinto ,&nbsp;Amie Hiller ,&nbsp;Charles K. Meshul","doi":"10.1016/j.mcn.2023.103883","DOIUrl":"10.1016/j.mcn.2023.103883","url":null,"abstract":"<div><p><span>There is growing interest in the use of natural products for the treatment of Parkinson's disease (PD). </span><span><em>Mucuna</em><em> pruriens</em></span><span> has been used in the treatment of humans with PD. The goal of this study was to determine if daily oral treatment with an extract of </span><em>Mucuna pruriens</em><span><span><span>, starting after the MPTP-induced loss of nigrostriatal dopamine in male mice, would result in recovery/restoration of motor function, tyrosine hydroxylase<span> (TH) protein expression in the </span></span>nigrostriatal pathway, or </span>glutamate<span><span> biomarkers in both the striatum and motor cortex. Following </span>MPTP administration, resulting in an 80 % loss of striatal TH, treatment with </span></span><em>Mucuna pruriens</em><span> failed to rescue either striatal TH or the dopamine transporter<span> back to the control levels, but there was restoration of gait/motor function. There was an MPTP-induced loss of TH-labeled neurons in the substantia nigra pars compacta<span> and in the number of striatal dendritic spines, both of which failed to be recovered following treatment with </span></span></span><em>Mucuna pruriens</em>. This <em>Mucuna pruriens</em><span>-induced locomotor recovery following MPTP was associated with restoration of two striatal glutamate transporter proteins<span><span>, GLAST (EAAT1) and EAAC1 (EAAT3), and the </span>vesicular glutamate transporter 2 (Vglut2) within the motor cortex. Post-MPTP treatment with </span></span><em>Mucuna pruriens</em>, results in locomotor improvement that is associated with recovery of striatal and motor cortex glutamate transporters but is independent of nigrostriatal TH restoration.</p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"126 ","pages":"Article 103883"},"PeriodicalIF":3.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10166333","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}