Neuronal signaling最新文献

Neural mechanisms of dopamine function in learning and memory in Caenorhabditis elegans 多巴胺在秀丽隐杆线虫学习和记忆中发挥作用的神经机制

Neuronal signaling Pub Date : 2023-12-11 DOI: 10.1042/ns20230057

Anna McMillen, Yee Lian Chew

{"title":"Neural mechanisms of dopamine function in learning and memory in Caenorhabditis elegans","authors":"Anna McMillen, Yee Lian Chew","doi":"10.1042/ns20230057","DOIUrl":"https://doi.org/10.1042/ns20230057","url":null,"abstract":"Research into learning and memory over the past decades has revealed key neurotransmitters that regulate these processes, many of which are evolutionarily conserved across diverse species. The monoamine neurotransmitter dopamine is one example of this, with countless studies demonstrating its importance in regulating behavioural plasticity. However, dopaminergic neural networks in the mammalian brain consist of hundreds or thousands of neurons, and thus cannot be studied at the level of single neurons acting within defined neural circuits. The nematode Caenorhabditis elegans has an experimentally tractable nervous system with a completely characterised synaptic connectome. This makes it an advantageous system to undertake mechanistic studies into how dopamine encodes lasting yet flexible behavioural plasticity in the nervous system. In this Review, we synthesise the research to date exploring the importance of dopaminergic signalling in learning, memory formation, and forgetting, focusing on research in C. elegans. We also explore the potential for dopamine-specific fluorescent biosensors in C. elegans to visualise dopaminergic neural circuits during learning and memory formation, in real-time. We propose that the use of these sensors in C. elegans, in combination with optogenetic and other light-based approaches, will further illuminate the detailed spatiotemporal requirements for encoding behavioural plasticity in an accessible experimental system. Understanding the key molecules and circuit mechanisms that regulate learning and forgetting in more compact invertebrate nervous systems may reveal new druggable targets for enhancing memory storage and delaying memory loss in bigger brains.","PeriodicalId":74287,"journal":{"name":"Neuronal signaling","volume":"100 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138981512","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}

引用次数: 0

Cytokine activity in Parkinson's disease. 帕金森病的细胞因子活性。

Neuronal signaling Pub Date : 2023-12-04 eCollection Date: 2023-12-01 DOI: 10.1042/NS20220063

Nicolas Dzamko

引用次数: 0

Modelling Alzheimer’s disease in a Dish – Dissecting Amyloid-β Metabolism in Human Neurons 在培养皿中模拟阿尔茨海默病--剖析人类神经元中的淀粉样蛋白-β代谢过程

Neuronal signaling Pub Date : 2023-11-28 DOI: 10.1042/ns20230020

Elizabeth Hill, Thomas J Cunningham

引用次数: 0

Inflammation and emotion regulation: a narrative review of evidence and mechanisms in emotion dysregulation disorders 炎症和情绪调节:情绪失调障碍的证据和机制的叙述性回顾

Neuronal signaling Pub Date : 2023-10-27 DOI: 10.1042/ns20220077

Flavia Petruso, Alexis Elena Giff, Beatrice Annunziata Milano, Maurilio Menduni De Rossi, Luigi Francesco Saccaro

{"title":"Inflammation and emotion regulation: a narrative review of evidence and mechanisms in emotion dysregulation disorders","authors":"Flavia Petruso, Alexis Elena Giff, Beatrice Annunziata Milano, Maurilio Menduni De Rossi, Luigi Francesco Saccaro","doi":"10.1042/ns20220077","DOIUrl":"https://doi.org/10.1042/ns20220077","url":null,"abstract":"Emotion dysregulation (ED) describes a difficulty with the modulation of which emotions are felt, as well as when and how these emotions are experienced or expressed. It is a focal overarching symptom in many severe and prevalent neuropsychiatric diseases, including bipolar disorders (BD), attention deficit/hyperactivity disorder (ADHD), and borderline personality disorder (BPD). In all these disorders, ED can manifest through symptoms of depression, anxiety, or affective lability. Considering the many symptomatic similarities between BD, ADHD, and BPD, a transdiagnostic approach is a promising lens of investigation. Mounting evidence supports the role of peripheral inflammatory markers and stress in the multifactorial aetiology and physiopathology of BD, ADHD, and BPD. Of note, neural circuits that regulate emotions appear particularly vulnerable to inflammatory insults and peripheral inflammation, which can impact the neuroimmune milieu of the central nervous system. Thus far, few studies have examined the link between ED and inflammation in BD, ADHD, and BPD. To our knowledge, no specific work has provided a critical comparison of the results from these disorders. To fill this gap in the literature, we review the known associations and mechanisms linking ED and inflammation in general, and clinically, in BD, ADHD, and BD. Our narrative review begins with an examination of the routes linking ED and inflammation, followed by a discussion of disorder-specific results accounting for methodological limitations and relevant confounding factors. Finally, we critically discuss both correspondences and discrepancies in the results and comment on potential vulnerability markers and promising therapeutic interventions.","PeriodicalId":74287,"journal":{"name":"Neuronal signaling","volume":"13 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136262499","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}

引用次数: 0

Inhibition of insulin-degrading enzyme in human neurons promotes amyloid-β deposition. 抑制人类神经元中的胰岛素降解酶可促进淀粉样蛋白-β的沉积。

Neuronal signaling Pub Date : 2023-10-03 eCollection Date: 2023-12-01 DOI: 10.1042/NS20230016

Helen A Rowland, Samuel R Moxon, Nicola J Corbett, Kelsey Hanson, Kate Fisher, Katherine A B Kellett, Nigel M Hooper

{"title":"Inhibition of insulin-degrading enzyme in human neurons promotes amyloid-β deposition.","authors":"Helen A Rowland, Samuel R Moxon, Nicola J Corbett, Kelsey Hanson, Kate Fisher, Katherine A B Kellett, Nigel M Hooper","doi":"10.1042/NS20230016","DOIUrl":"10.1042/NS20230016","url":null,"abstract":"Alzheimer's disease (AD) is characterised by the aggregation and deposition of amyloid-β (Aβ) peptides in the human brain. In age-related late-onset AD, deficient degradation and clearance, rather than enhanced production, of Aβ contributes to disease pathology. In the present study, we assessed the contribution of the two key Aβ-degrading zinc metalloproteases, insulin-degrading enzyme (IDE) and neprilysin (NEP), to Aβ degradation in human induced pluripotent stem cell (iPSC)-derived cortical neurons. Using an Aβ fluorescence polarisation assay, inhibition of IDE but not of NEP, blocked the degradation of Aβ by human neurons. When the neurons were grown in a 3D extracellular matrix to visualise Aβ deposition, inhibition of IDE but not NEP, increased the number of Aβ deposits. The resulting Aβ deposits were stained with the conformation-dependent, anti-amyloid antibodies A11 and OC that recognise Aβ aggregates in the human AD brain. Inhibition of the Aβ-forming β-secretase prevented the formation of the IDE-inhibited Aβ deposits. These data indicate that inhibition of IDE in live human neurons grown in a 3D matrix increased the deposition of Aβ derived from the proteolytic cleavage of the amyloid precursor protein. This work has implications for strategies aimed at enhancing IDE activity to promote Aβ degradation in AD.","PeriodicalId":74287,"journal":{"name":"Neuronal signaling","volume":"7 4","pages":"NS20230016"},"PeriodicalIF":0.0,"publicationDate":"2023-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10550784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41159874","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: 0

Modeling Parkinson's disease in LRRK2 rodents. LRRK2啮齿动物帕金森病模型。

Neuronal signaling Pub Date : 2023-09-01 DOI: 10.1042/NS20220040

Chiara Domenicale, Stefano Magnabosco, Michele Morari

{"title":"Modeling Parkinson's disease in LRRK2 rodents.","authors":"Chiara Domenicale, Stefano Magnabosco, Michele Morari","doi":"10.1042/NS20220040","DOIUrl":"https://doi.org/10.1042/NS20220040","url":null,"abstract":"Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are associated with familial and sporadic forms of Parkinson's disease (PD). Sporadic PD and LRRK2 PD share main clinical and neuropathological features, namely hypokinesia, degeneration of nigro-striatal dopamine neurons and α-synuclein aggregates in the form of Lewy bodies. Animals harboring the most common LRRK2 mutations, i.e. p.G2019S and p.R1441C/G, have been generated to replicate the parkinsonian phenotype and investigate the underlying pathogenic mechanisms. Disappointingly, however, LRRK2 rodents did not consistently phenocopy hypokinesia and nigro-striatal degeneration, or showed Lewy body-like aggregates. Instead, LRRK2 rodents manifested non-motor signs and dysregulated transmission at dopaminergic and non-dopaminergic synapses that are reminiscent of behavioral and functional network changes observed in the prodromal phase of the disease. LRRK2 rodents also manifested greater susceptibility to different parkinsonian toxins or stressors when subjected to dual-hit or multiple-hit protocols, confirming LRRK2 mutations as genetic risk factors. In conclusion, LRRK2 rodents represent a unique tool to identify the molecular mechanisms through which LRRK2 modulates the course and clinical presentations of PD and to study the interplay between genetic, intrinsic and environmental protective/risk factors in PD pathogenesis.","PeriodicalId":74287,"journal":{"name":"Neuronal signaling","volume":"7 3","pages":"NS20220040"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10432857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10048612","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: 0

Endocannabinoid signaling and epigenetics modifications in the neurobiology of stress-related disorders. 压力相关疾病神经生物学中的内源性大麻素信号转导和表观遗传学改变。

Neuronal signaling Pub Date : 2023-07-25 eCollection Date: 2023-07-01 DOI: 10.1042/NS20220034

Arthur A Coelho, Sávio Lima-Bastos, Pedro H Gobira, Sabrina F Lisboa

{"title":"Endocannabinoid signaling and epigenetics modifications in the neurobiology of stress-related disorders.","authors":"Arthur A Coelho, Sávio Lima-Bastos, Pedro H Gobira, Sabrina F Lisboa","doi":"10.1042/NS20220034","DOIUrl":"10.1042/NS20220034","url":null,"abstract":"Stress exposure is associated with psychiatric conditions, such as depression, anxiety, and post-traumatic stress disorder (PTSD). It is also a vulnerability factor to developing or reinstating substance use disorder. Stress causes several changes in the neuro-immune-endocrine axis, potentially resulting in prolonged dysfunction and diseases. Changes in several transmitters, including serotonin, dopamine, glutamate, gamma-aminobutyric acid (GABA), glucocorticoids, and cytokines, are associated with psychiatric disorders or behavioral alterations in preclinical studies. Complex and interacting mechanisms make it very difficult to understand the physiopathology of psychiatry conditions; therefore, studying regulatory mechanisms that impact these alterations is a good approach. In the last decades, the impact of stress on biology through epigenetic markers, which directly impact gene expression, is under intense investigation; these mechanisms are associated with behavioral alterations in animal models after stress or drug exposure, for example. The endocannabinoid (eCB) system modulates stress response, reward circuits, and other physiological functions, including hypothalamus-pituitary-adrenal axis activation and immune response. eCBs, for example, act retrogradely at presynaptic neurons, limiting the release of neurotransmitters, a mechanism implicated in the antidepressant and anxiolytic effects after stress. Epigenetic mechanisms can impact the expression of eCB system molecules, which in turn can regulate epigenetic mechanisms. This review will present evidence of how the eCB system and epigenetic mechanisms interact and the consequences of this interaction in modulating behavioral changes after stress exposure in preclinical studies or psychiatric conditions. Moreover, evidence that correlates the involvement of the eCB system and epigenetic mechanisms in drug abuse contexts will be discussed.","PeriodicalId":74287,"journal":{"name":"Neuronal signaling","volume":"7 2","pages":"NS20220034"},"PeriodicalIF":0.0,"publicationDate":"2023-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10372471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9963934","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: 0

Paternal early life stress exerts intergenerational effects on male C57Bl/6J offspring risk-taking behaviors and predator scent-induced c-Fos expression. 父亲早期生活压力对雄性C57Bl/6J后代冒险行为和捕食者气味诱导的c-Fos表达具有代际影响。

Neuronal signaling Pub Date : 2023-07-01 DOI: 10.1042/NS20220097

Ulysse M C C Thivisol, Phoebe Ho, Baijia Li, Mari Trompke, Lucas B Hoffmann, Anthony J Hannan, Terence Y Pang

{"title":"Paternal early life stress exerts intergenerational effects on male C57Bl/6J offspring risk-taking behaviors and predator scent-induced c-Fos expression.","authors":"Ulysse M C C Thivisol, Phoebe Ho, Baijia Li, Mari Trompke, Lucas B Hoffmann, Anthony J Hannan, Terence Y Pang","doi":"10.1042/NS20220097","DOIUrl":"https://doi.org/10.1042/NS20220097","url":null,"abstract":"Paternal preconceptional health factors, such as exposures to stress, diet and exercise, have been found to significantly influence offspring phenotypes in a range of animal models. Preclinical studies have provided evidence that paternal stress is associated with increased stress responsivity and anxiety-related traits, particularly in male offspring. It was previously reported that a paternal history of maternal separation (MS) led to male offspring (PatMS) displaying reduced cautious behavior during exploration of a novel environment. The neural basis for that absence of behavioral moderation is unclear. Here, we investigated the adaptive behavioral responses of control and PatMS male offspring in the predator odor risk-assessment task (PORT). PatMS mice failed to moderate their behaviors in the presence of a predator odor 2,4,5-trimethylthiazoline (TMT). c-Fos mapping revealed reduced cellular activation in fear-regulating brain regions of PatMS mice, such as in the cingulate cortex, dentate gyrus of the hippocampus and the basolateral amygdala. Expression of the paternally imprinted gene Grb10 (previously identified as a key molecular regulator of risk-taking behavior) was unaltered in PatMS mice. However, other paternal imprinted genes such as Igf2 and PEG3 were differentially expressed in PatMS mice. Overall, our study provides the first evidence of an intergenerational influence of preconceptional paternal stress exposure on offspring brain zunction relevant to risk-taking behavior, which is also independent of Grb10 gene expression.","PeriodicalId":74287,"journal":{"name":"Neuronal signaling","volume":"7 2","pages":"NS20220097"},"PeriodicalIF":0.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10154287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9423074","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: 0

Inflammation in the pathogenesis of depression: a disorder of neuroimmune origin. 抑郁症发病机制中的炎症:一种神经免疫起源的紊乱。

Neuronal signaling Pub Date : 2023-07-01 DOI: 10.1042/NS20220054

Myles Corrigan, Aoife M O'Rourke, Barry Moran, Jean M Fletcher, Andrew Harkin

{"title":"Inflammation in the pathogenesis of depression: a disorder of neuroimmune origin.","authors":"Myles Corrigan, Aoife M O'Rourke, Barry Moran, Jean M Fletcher, Andrew Harkin","doi":"10.1042/NS20220054","DOIUrl":"https://doi.org/10.1042/NS20220054","url":null,"abstract":"There are several hypotheses concerning the underlying pathophysiological mechanisms of major depression, which centre largely around adaptive changes in neuronal transmission and plasticity, neurogenesis, and circuit and regional connectivity. The immune and endocrine systems are commonly implicated in driving these changes. An intricate interaction of stress hormones, innate immune cells and the actions of soluble mediators of immunity within the nervous system is described as being associated with the symptoms of depression. Bridging endocrine and immune processes to neurotransmission and signalling within key cortical and limbic brain circuits are critical to understanding depression as a disorder of neuroimmune origins. Emergent areas of research include a growing recognition of the adaptive immune system, advances in neuroimaging techniques and mechanistic insights gained from transgenic animals. Elucidation of glial-neuronal interactions is providing additional avenues into promising areas of research, the development of clinically relevant disease models and the discovery of novel therapies. This narrative review focuses on molecular and cellular mechanisms that are influenced by inflammation and stress. The aim of this review is to provide an overview of our current understanding of depression as a disorder of neuroimmune origin, focusing on neuroendocrine and neuroimmune dysregulation in depression pathophysiology. Advances in current understanding lie in pursuit of relevant biomarkers, as the potential of biomarker signatures to improve clinical outcomes is yet to be fully realised. Further investigations to expand biomarker panels including integration with neuroimaging, utilising individual symptoms to stratify patients into more homogenous subpopulations and targeting the immune system for new treatment approaches will help to address current unmet clinical need.","PeriodicalId":74287,"journal":{"name":"Neuronal signaling","volume":"7 2","pages":"NS20220054"},"PeriodicalIF":0.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10345431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9881521","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: 1

Maternal immune activation and role of placenta in the prenatal programming of neurodevelopmental disorders. 母体免疫激活和胎盘在神经发育障碍产前编程中的作用。

Neuronal signaling Pub Date : 2023-05-31 eCollection Date: 2023-07-01 DOI: 10.1042/NS20220064

Rebecca M Woods, Jarred M Lorusso, Jennifer Fletcher, Heidi ElTaher, Francesca McEwan, Isabella Harris, Hager M Kowash, Stephen W D'Souza, Michael Harte, Reinmar Hager, Jocelyn D Glazier

{"title":"Maternal immune activation and role of placenta in the prenatal programming of neurodevelopmental disorders.","authors":"Rebecca M Woods, Jarred M Lorusso, Jennifer Fletcher, Heidi ElTaher, Francesca McEwan, Isabella Harris, Hager M Kowash, Stephen W D'Souza, Michael Harte, Reinmar Hager, Jocelyn D Glazier","doi":"10.1042/NS20220064","DOIUrl":"10.1042/NS20220064","url":null,"abstract":"Maternal infection during pregnancy, leading to maternal immune activation (mIA) and cytokine release, increases the offspring risk of developing a variety of neurodevelopmental disorders (NDDs), including schizophrenia. Animal models have provided evidence to support these mechanistic links, with placental inflammatory responses and dysregulation of placental function implicated. This leads to changes in fetal brain cytokine balance and altered epigenetic regulation of key neurodevelopmental pathways. The prenatal timing of such mIA-evoked changes, and the accompanying fetal developmental responses to an altered in utero environment, will determine the scope of the impacts on neurodevelopmental processes. Such dysregulation can impart enduring neuropathological changes, which manifest subsequently in the postnatal period as altered neurodevelopmental behaviours in the offspring. Hence, elucidation of the functional changes that occur at the molecular level in the placenta is vital in improving our understanding of the mechanisms that underlie the pathogenesis of NDDs. This has notable relevance to the recent COVID-19 pandemic, where inflammatory responses in the placenta to SARS-CoV-2 infection during pregnancy and NDDs in early childhood have been reported. This review presents an integrated overview of these collective topics and describes the possible contribution of prenatal programming through placental effects as an underlying mechanism that links to NDD risk, underpinned by altered epigenetic regulation of neurodevelopmental pathways.","PeriodicalId":74287,"journal":{"name":"Neuronal signaling","volume":"7 2","pages":"NS20220064"},"PeriodicalIF":0.0,"publicationDate":"2023-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10273029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9653913","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: 0