Neuronal signaling最新文献_第5页

Mitochondrial and metabolic dysfunction in Friedreich ataxia: update on pathophysiological relevance and clinical interventions. 弗里德里希共济失调的线粒体和代谢功能障碍:病理生理学相关性和临床干预的最新进展。

Neuronal signaling Pub Date : 2021-05-17 eCollection Date: 2021-06-01 DOI: 10.1042/NS20200093

David R Lynch, Garrett Farmer

{"title":"Mitochondrial and metabolic dysfunction in Friedreich ataxia: update on pathophysiological relevance and clinical interventions.","authors":"David R Lynch, Garrett Farmer","doi":"10.1042/NS20200093","DOIUrl":"https://doi.org/10.1042/NS20200093","url":null,"abstract":"Friedreich ataxia (FRDA) is a recessive disorder resulting from relative deficiency of the mitochondrial protein frataxin. Frataxin functions in the process of iron-sulfur (Fe-S) cluster synthesis. In this review, we update some of the processes downstream of frataxin deficiency that may mediate the pathophysiology. Based on cellular models, in vivo models and observations of patients, ferroptosis may play a major role in the pathogenesis of FRDA along with depletion of antioxidant reserves and abnormalities of mitochondrial biogenesis. Ongoing clinical trials with ferroptosis inhibitors and nuclear factor erythroid 2-related factor 2 (Nrf2) activators are now targeting each of the processes. In addition, better understanding of the mitochondrial events in FRDA may allow the development of improved imaging methodology for assessing the disorder. Though not technologically feasible at present, metabolic imaging approaches may provide a direct methodology to understand the mitochondrial changes occurring in FRDA and provide a methodology to monitor upcoming trials of frataxin restoration.","PeriodicalId":74287,"journal":{"name":"Neuronal signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38945565","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}

引用次数: 15

Back to the future: lessons from past viral infections and the link with Parkinson's disease. 回到未来:过去病毒感染的教训及其与帕金森病的联系。

Neuronal signaling Pub Date : 2021-04-16 eCollection Date: 2021-04-01 DOI: 10.1042/NS20200051

Eilis Dowd, Declan P McKernan

引用次数: 4

Signalling pathways contributing to learning and memory deficits in the Ts65Dn mouse model of Down syndrome. 唐氏综合征Ts65Dn小鼠模型中导致学习和记忆缺陷的信号通路

Neuronal signaling Pub Date : 2021-03-12 eCollection Date: 2021-04-01 DOI: 10.1042/NS20200011

Aimée Freeburn, Robert Gordon Keith Munn

{"title":"Signalling pathways contributing to learning and memory deficits in the Ts65Dn mouse model of Down syndrome.","authors":"Aimée Freeburn, Robert Gordon Keith Munn","doi":"10.1042/NS20200011","DOIUrl":"https://doi.org/10.1042/NS20200011","url":null,"abstract":"Down syndrome (DS) is a genetic trisomic disorder that produces life-long changes in physiology and cognition. Many of the changes in learning and memory seen in DS are reminiscent of disorders involving the hippocampal/entorhinal circuit. Mouse models of DS typically involve trisomy of murine chromosome 16 is homologous for many of the genes triplicated in human trisomy 21, and provide us with good models of changes in, and potential pharmacotherapy for, human DS. Recent careful dissection of the Ts65Dn mouse model of DS has revealed differences in key signalling pathways from the basal forebrain to the hippocampus and associated rhinal cortices, as well as changes in the microstructure of the hippocampus itself. In vivo behavioural and electrophysiological studies have shown that Ts65Dn animals have difficulties in spatial memory that mirror hippocampal deficits, and have changes in hippocampal electrophysiological phenomenology that may explain these differences, and align with expectations generated from in vitro exploration of this model. Finally, given the existing data, we will examine the possibility for pharmacotherapy for DS, and outline the work that remains to be done to fully understand this system.","PeriodicalId":74287,"journal":{"name":"Neuronal signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25513674","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}

引用次数: 4

The life cycle of voltage-gated Ca²⁺ channels in neurons: an update on the trafficking of neuronal calcium channels. 神经元中电压门控 Ca2+ 通道的生命周期：神经元钙通道迁移的最新进展。

Neuronal signaling Pub Date : 2021-02-23 eCollection Date: 2021-04-01 DOI: 10.1042/NS20200095

Laurent Ferron, Saloni Koshti, Gerald W Zamponi

引用次数: 0

Neuronal Signaling: A reflection on the Biochemical Society's newest journal and an exciting outlook on its next steps. 神经元信号:对生化学会最新期刊的反思和对其下一步的令人兴奋的展望。

Neuronal signaling Pub Date : 2021-02-08 eCollection Date: 2021-04-01 DOI: 10.1042/NS20210007

Aideen M Sullivan, S Clare Stanford

引用次数: 0

Neuroprotective function of microglia in the developing brain. 小胶质细胞在大脑发育中的神经保护功能。

Neuronal signaling Pub Date : 2021-01-22 eCollection Date: 2021-04-01 DOI: 10.1042/NS20200024

Yuki Fujita, Toshihide Yamashita

引用次数: 12

Exercise alters LPS-induced glial activation in the mouse brain. 运动改变lps诱导的小鼠大脑神经胶质活化。

Neuronal signaling Pub Date : 2020-12-02 eCollection Date: 2020-12-01 DOI: 10.1042/NS20200003

Bibiana C Mota, Áine M Kelly

{"title":"Exercise alters LPS-induced glial activation in the mouse brain.","authors":"Bibiana C Mota, Áine M Kelly","doi":"10.1042/NS20200003","DOIUrl":"https://doi.org/10.1042/NS20200003","url":null,"abstract":"Experimental and epidemiological evidence suggest that modifiable lifestyle factors, including physical exercise, can build structural and cognitive reserve in the brain, increasing resilience to injury and insult. Accordingly, exercise can reduce the increased expression of proinflammatory cytokines in the brain associated with ageing or experimentally induced neuroinflammation. However, the cellular mechanisms by which exercise exerts this effect are unknown, including the effects of exercise on classic or alternative activation of astrocytes and microglia. In the present study, we assess the effects of nine consecutive days of treadmill running on the glial cell response to a single systemic injection of lipopolysaccharide (LPS) and, in parallel, the effects on spatial learning and memory. We show that prior exercise protects against LPS-induced impairment of performance in the object displacement task concomitant with attenuation of IL-1β, TNFα and IL-10 mRNA expression in the hippocampus. Assessment of isolated astrocytes and microglia revealed that LPS induced a proinflammatory response in these cells that was not observed in cells prepared from the brains of mice who had undergone prior exercise. The results suggest that exercise modulates neuroinflammation by reducing the proinflammatory microglial response, suggesting a mechanism by which exercise may be neuroprotective.","PeriodicalId":74287,"journal":{"name":"Neuronal signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38698591","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}

引用次数: 9

Lactobacillus rhamnosus GG soluble mediators ameliorate early life stress-induced visceral hypersensitivity and changes in spinal cord gene expression. 鼠李糖乳杆菌GG可溶性介质改善生命早期应激诱导的内脏超敏反应和脊髓基因表达的变化。

Neuronal signaling Pub Date : 2020-11-23 eCollection Date: 2020-12-01 DOI: 10.1042/NS20200007

Karen-Anne McVey Neufeld, Conall R Strain, Matteo M Pusceddu, Rosaline V Waworuntu, Sarmauli Manurung, Gabriele Gross, Gerry M Moloney, Alan E Hoban, Kiera Murphy, Catherine Stanton, Timothy G Dinan, John F Cryan, Siobhain M O'Mahony

{"title":"Lactobacillus rhamnosus GG soluble mediators ameliorate early life stress-induced visceral hypersensitivity and changes in spinal cord gene expression.","authors":"Karen-Anne McVey Neufeld, Conall R Strain, Matteo M Pusceddu, Rosaline V Waworuntu, Sarmauli Manurung, Gabriele Gross, Gerry M Moloney, Alan E Hoban, Kiera Murphy, Catherine Stanton, Timothy G Dinan, John F Cryan, Siobhain M O'Mahony","doi":"10.1042/NS20200007","DOIUrl":"https://doi.org/10.1042/NS20200007","url":null,"abstract":"Visceral hypersensitivity is a hallmark of many functional and stress-related gastrointestinal disorders, and there is growing evidence that the gut microbiota may play a role in its pathophysiology. It has previously been shown that early life stress-induced visceral sensitivity is reduced by various probiotic strains of bacteria (including Lactobacillus rhamnosus GG (LGG)) alone or in combination with prebiotic fibres in rat models. However, the exact mechanisms underpinning such effects remain unresolved. Here, we investigated if soluble mediators derived from LGG can mimic the bacteria's effects on visceral hypersensitivity and the microbiota-gut-brain axis. Rats were exposed to maternal separation (MS) from postnatal days 2-12. From weaning onwards both non-separated (NS) and MS offspring were provided drinking water with or without supplementation of standardized preparations of the LGG soluble mediators (LSM). Our results show that MS led to increased visceral sensitivity and exaggerated corticosterone plasma levels following restraint stress in adulthood, and both of these effects were ameliorated through LSM supplementation. Differential regulation of various genes in the spinal cord of MS versus NS rats was observed, 41 of which were reversed by LSM supplementation. At the microbiota composition level MS led to changes in beta diversity and abundance of specific bacteria including parabacteroides, which were ameliorated by LSM. These findings support probiotic soluble mediators as potential interventions in the reduction of symptoms of visceral hypersensitivity.","PeriodicalId":74287,"journal":{"name":"Neuronal signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38735031","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}

引用次数: 10

New developments in Huntington's disease and other triplet repeat diseases: DNA repair turns to the dark side. 亨廷顿氏病和其他三重重复疾病的新进展:DNA修复转向阴暗面。

Neuronal signaling Pub Date : 2020-11-16 eCollection Date: 2020-12-01 DOI: 10.1042/NS20200010

Robert S Lahue

{"title":"New developments in Huntington's disease and other triplet repeat diseases: DNA repair turns to the dark side.","authors":"Robert S Lahue","doi":"10.1042/NS20200010","DOIUrl":"https://doi.org/10.1042/NS20200010","url":null,"abstract":"Huntington's disease (HD) is a fatal, inherited neurodegenerative disease that causes neuronal death, particularly in medium spiny neurons. HD leads to serious and progressive motor, cognitive and psychiatric symptoms. Its genetic basis is an expansion of the CAG triplet repeat in the HTT gene, leading to extra glutamines in the huntingtin protein. HD is one of nine genetic diseases in this polyglutamine (polyQ) category, that also includes a number of inherited spinocerebellar ataxias (SCAs). Traditionally it has been assumed that HD age of onset and disease progression were solely the outcome of age-dependent exposure of neurons to toxic effects of the inherited mutant huntingtin protein. However, recent genome-wide association studies (GWAS) have revealed significant effects of genetic variants outside of HTT. Surprisingly, these variants turn out to be mostly in genes encoding DNA repair factors, suggesting that at least some disease modulation occurs at the level of the HTT DNA itself. These DNA repair proteins are known from model systems to promote ongoing somatic CAG repeat expansions in tissues affected by HD. Thus, for triplet repeats, some DNA repair proteins seem to abandon their normal genoprotective roles and, instead, drive expansions and accelerate disease. One attractive hypothesis-still to be proven rigorously-is that somatic HTT expansions augment the disease burden of the inherited allele. If so, therapeutic approaches that lower levels of huntingtin protein may need blending with additional therapies that reduce levels of somatic CAG repeat expansions to achieve maximal effect.","PeriodicalId":74287,"journal":{"name":"Neuronal signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38641101","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}

引用次数: 10

Auditory fear conditioning alters neural gain in the cochlear nucleus: a wireless neural recording study in freely behaving rats. 听觉恐惧调节改变了耳蜗核的神经增益:对自由行为的大鼠的无线神经记录研究。

Neuronal signaling Pub Date : 2020-11-16 eCollection Date: 2020-12-01 DOI: 10.1042/NS20200009

Antonio G Paolini, Simeon J Morgan, Jee Hyun Kim

{"title":"Auditory fear conditioning alters neural gain in the cochlear nucleus: a wireless neural recording study in freely behaving rats.","authors":"Antonio G Paolini, Simeon J Morgan, Jee Hyun Kim","doi":"10.1042/NS20200009","DOIUrl":"https://doi.org/10.1042/NS20200009","url":null,"abstract":"Anxiety disorders involve distorted perception of the world including increased saliency of stress-associated cues. However, plasticity in the initial sensory regions of the brain following a fearful experience has never been examined. The cochlear nucleus (CN) is the first station in the central auditory system, with heterogeneous collections of neurons that not only project to but also receive projections from cortico-limbic regions, suggesting a potential for experience-dependent plasticity. Using wireless neural recordings in freely behaving rats, we demonstrate for the first time that neural gain in the CN is significantly altered by fear conditioning to auditory sequences. Specifically, the ventral subnuclei significantly increased firing rate to the conditioned tone sequence, while the dorsal subnuclei significantly decreased firing rate during the conditioning session overall. These findings suggest subregion-specific changes in the balance of inhibition and excitation in the CN as a result of conditioning experience. Heart rate was measured as the conditioned response (CR), which showed that while pre-conditioned stimulus (CS) responding did not change across baseline and conditioning sessions, significant changes in heart rate were observed to the tone sequence followed by shock. Heart-rate findings support acquisition of conditioned fear. Taken together, the present study presents first evidence for potential experience-dependent changes in auditory perception that involve novel plasticity within the first site of processing auditory information in the brain.","PeriodicalId":74287,"journal":{"name":"Neuronal signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7681204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38672353","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}

引用次数: 3