Journal of Neuroscience Research最新文献_第6页

Heterogeneity of brain extracellular matrix and astrocyte activation 脑细胞外基质和星形胶质细胞活化的异质性

IF 4.2 3区医学

Journal of Neuroscience Research Pub Date : 2024-05-21 DOI: 10.1002/jnr.25356

Rebecca E. Huber, Courtney Babbitt, Shelly R. Peyton

{"title":"Heterogeneity of brain extracellular matrix and astrocyte activation","authors":"Rebecca E. Huber, Courtney Babbitt, Shelly R. Peyton","doi":"10.1002/jnr.25356","DOIUrl":"10.1002/jnr.25356","url":null,"abstract":"From the blood brain barrier to the synaptic space, astrocytes provide structural, metabolic, ionic, and extracellular matrix (ECM) support across the brain. Astrocytes include a vast array of subtypes, their phenotypes and functions varying both regionally and temporally. Astrocytes' metabolic and regulatory functions poise them to be quick and sensitive responders to injury and disease in the brain as revealed by single cell sequencing. Far less is known about the influence of the local healthy and aging microenvironments on these astrocyte activation states. In this forward-looking review, we describe the known relationship between astrocytes and their local microenvironment, the remodeling of the microenvironment during disease and injury, and postulate how they may drive astrocyte activation. We suggest technology development to better understand the dynamic diversity of astrocyte activation states, and how basal and activation states depend on the ECM microenvironment. A deeper understanding of astrocyte response to stimuli in ECM-specific contexts (brain region, age, and sex of individual), paves the way to revolutionize how the field considers astrocyte-ECM interactions in brain injury and disease and opens routes to return astrocytes to a healthy quiescent state.","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"102 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141076018","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}

引用次数: 0

Divergent association between pain intensity and resting-state fMRI-based brain entropy in different age groups 不同年龄组的疼痛强度与基于静息态 fMRI 的大脑熵之间存在差异。

IF 4.2 3区医学

Journal of Neuroscience Research Pub Date : 2024-05-15 DOI: 10.1002/jnr.25341

Gianpaolo Del Mauro, Landrew Samuel Sevel, Jeff Boissoneault, Ze Wang

{"title":"Divergent association between pain intensity and resting-state fMRI-based brain entropy in different age groups","authors":"Gianpaolo Del Mauro, Landrew Samuel Sevel, Jeff Boissoneault, Ze Wang","doi":"10.1002/jnr.25341","DOIUrl":"10.1002/jnr.25341","url":null,"abstract":"Pain is a multidimensional subjective experience sustained by multiple brain regions involved in different aspects of pain experience. We used brain entropy (BEN) estimated from resting-state fMRI (rsfMRI) data to investigate the neural correlates of pain experience. BEN was estimated from rs-fMRI data provided by two datasets with different age range: the Human Connectome Project-Young Adult (HCP-YA) and the Human Connectome project-Aging (HCP-A) datasets. Retrospective assessment of experienced pain intensity was retrieved from both datasets. No main effect of pain intensity was observed. The interaction between pain and age, however, was related to increased BEN in several pain-related brain regions, reflecting greater variability of spontaneous brain activity. Dividing the sample into a young adult group (YG) and a middle age-aging group (MAG) resulted in two divergent patterns of pain–BEN association: In the YG, pain intensity was related to reduced BEN in brain regions involved in the sensory processing of pain; in the MAG, pain was associated with increased BEN in areas related to both sensory and cognitive aspects of pain experience.","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"102 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140945369","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}

引用次数: 0

Implications of environmental nanoparticles on neurodegeneration 环境纳米粒子对神经退化的影响。

IF 4.2 3区医学

Journal of Neuroscience Research Pub Date : 2024-05-15 DOI: 10.1002/jnr.25340

Cristina Hermosillo-Abundis, Miguel A. Méndez-Rojas, Oscar Arias-Carrión

引用次数: 0

The differential effects of palmitic acid and oleic acid on the metabolic response of hypothalamic astrocytes from male and female mice 棕榈酸和油酸对雌雄小鼠下丘脑星形胶质细胞代谢反应的不同影响

IF 4.2 3区医学

Journal of Neuroscience Research Pub Date : 2024-05-14 DOI: 10.1002/jnr.25339

Roberto Collado-Perez, David Chamoso-Sánchez, Antonia García, María S. Fernández-Alfonso, Maria Jiménez-Hernáiz, Sandra Canelles, Jesús Argente, Laura M. Frago, Julie A. Chowen

{"title":"The differential effects of palmitic acid and oleic acid on the metabolic response of hypothalamic astrocytes from male and female mice","authors":"Roberto Collado-Perez, David Chamoso-Sánchez, Antonia García, María S. Fernández-Alfonso, Maria Jiménez-Hernáiz, Sandra Canelles, Jesús Argente, Laura M. Frago, Julie A. Chowen","doi":"10.1002/jnr.25339","DOIUrl":"10.1002/jnr.25339","url":null,"abstract":"Diets rich in saturated fats are more detrimental to health than those containing mono- or unsaturated fats. Fatty acids are an important source of energy, but they also relay information regarding nutritional status to hypothalamic metabolic circuits and when in excess can be detrimental to these circuits. Astrocytes are the main site of central fatty acid β-oxidation, and hypothalamic astrocytes participate in energy homeostasis, in part by modulating hormonal and nutritional signals reaching metabolic neurons, as well as in the inflammatory response to high-fat diets. Thus, we hypothesized that how hypothalamic astrocytes process-specific fatty acids participates in determining the differential metabolic response and that this is sex dependent as males and females respond differently to high-fat diets. Male and female primary hypothalamic astrocyte cultures were treated with oleic acid (OA) or palmitic acid (PA) for 24 h, and an untargeted metabolomics study was performed. A clear predictive model for PA exposure was obtained, while the metabolome after OA exposure was not different from controls. The observed modifications in metabolites, as well as the expression levels of key metabolic enzymes, indicate a reduction in the activity of the Krebs and glutamate/glutamine cycles in response to PA. In addition, there were specific differences between the response of astrocytes from male and female mice, as well as between hypothalamic and cerebral cortical astrocytes. Thus, the response of hypothalamic astrocytes to specific fatty acids could result in differential impacts on surrounding metabolic neurons and resulting in varied systemic metabolic outcomes.","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"102 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916857","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}

引用次数: 0

IDO-1 inhibition improves outcome after fluid percussion injury in adult male rats 抑制 IDO-1 可改善成年雄性大鼠体液冲击损伤后的疗效

IF 4.2 3区医学

Journal of Neuroscience Research Pub Date : 2024-05-06 DOI: 10.1002/jnr.25338

Marawan Sadek, Kurt R. Stover, Xiaojing Liu, Mark A. Reed, Donald F. Weaver, Aylin Y. Reid

{"title":"IDO-1 inhibition improves outcome after fluid percussion injury in adult male rats","authors":"Marawan Sadek, Kurt R. Stover, Xiaojing Liu, Mark A. Reed, Donald F. Weaver, Aylin Y. Reid","doi":"10.1002/jnr.25338","DOIUrl":"https://doi.org/10.1002/jnr.25338","url":null,"abstract":"The enzyme indoleamine 2,3 dioxygenase 1 (IDO1) catalyzes the rate-limiting step in the kynurenine pathway (KP) which produces both neuroprotective and neurotoxic metabolites. Neuroinflammatory signals produced as a result of pathological conditions can increase production of IDO1 and boost its enzymatic capacity. IDO1 and the KP have been implicated in behavioral recovery after human traumatic brain injury (TBI), but their roles in experimental models of TBI are for the most part unknown. We hypothesized there is an increase in KP activity in the fluid percussion injury (FPI) model of TBI, and that administration of an IDO1 inhibitor will improve neurological recovery. In this study, adult male Sprague Dawley rats were subjected to FPI or sham injury and received twice-daily oral administration of the IDO1 inhibitor PF-06840003 (100 mg/kg) or vehicle control. FPI resulted in a significant increase in KP activity, as demonstrated by an increased ratio of kynurenine: tryptophan, in the perilesional neocortex and ipsilateral hippocampus 3 days postinjury (DPI), which normalized by 7 DPI. The increase in KP activity was prevented by PF-06840003. IDO1 inhibition also improved memory performance as assessed in the Barnes maze and anxiety behaviors as assessed in open field testing in the first 28 DPI. These results suggest increased KP activity after FPI may mediate neurological dysfunction, and IDO1 inhibition should be further investigated as a potential therapeutic target to improve recovery.","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"102 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jnr.25338","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140844764","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}

引用次数: 0

Excessive intragastric alcohol administration exacerbates hepatic encephalopathy and provokes neuronal cell death in male rats with chronic liver disease 雄性慢性肝病大鼠胃内摄入过量酒精会加重肝性脑病并导致神经细胞死亡

IF 4.2 3区医学

Journal of Neuroscience Research Pub Date : 2024-04-29 DOI: 10.1002/jnr.25337

Farzaneh Tamnanloo, Xiaoru Chen, Mariana M. Oliveira, Mélanie Tremblay, Christopher F. Rose

{"title":"Excessive intragastric alcohol administration exacerbates hepatic encephalopathy and provokes neuronal cell death in male rats with chronic liver disease","authors":"Farzaneh Tamnanloo, Xiaoru Chen, Mariana M. Oliveira, Mélanie Tremblay, Christopher F. Rose","doi":"10.1002/jnr.25337","DOIUrl":"https://doi.org/10.1002/jnr.25337","url":null,"abstract":"Hepatic encephalopathy (HE) is defined as decline in neurological function during chronic liver disease (CLD). Alcohol is a major etiological factor in the pathogenesis of fibrosis/cirrhosis and has also been documented to directly impact the brain. However, the role of alcohol in the development of HE in CLD remains unclear. Here, we investigated the impact of excessive alcohol administration on neurological deterioration in rats with CLD. Starting day 7 post-BDL surgery, rats were administered alcohol twice daily (51% v/v ethanol, 3 g/kg, via gavage) for 4 weeks. Motor coordination was assessed weekly using rotarod and anxiety-like behavior was evaluated with open field and elevated plus maze at 5 weeks. Upon sacrifice, brains were collected for western blot and immunohistochemical analyses to investigate neuronal integrity and oxidative stress status. Alcohol worsened motor coordination performance and increased anxiety-like behavior in BDL rats. Impairments were associated with decreased neuronal markers of NeuN and SMI311, increased apoptotic markers of cleaved/pro-caspase-3 and Bax/Bcl2, increased necroptosis markers of pRIP3 and pMLKL, decreased total antioxidant capacity (TAC), and increased 4-hydroxynonenal (4-HNE)modified proteins in the cerebellum of BDL-alcohol rats when compared to respective controls. Immunofluorescence confirmed the colocalization of cleaved caspase-3 and pMLKL in the granular neurons of the cerebellum of BDL-alcohol rats. Excessive alcohol consumption exacerbates HE which leads to associated apoptotic and necroptotic neuronal loss in the cerebellum of BDL-alcohol rats. Additionally, higher levels of 4-HNE and decreased TAC in the cerebellum of BDL-alcohol rats suggest oxidative stress is the triggering factor of apoptotic and necroptotic neuronal loss/injury.","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"102 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jnr.25337","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140808157","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}

引用次数: 0

4R-cembranoid suppresses glial cells inflammatory phenotypes and prevents hippocampal neuronal loss in LPS-treated mice 4R-cembranoid 可抑制神经胶质细胞的炎症表型，防止经 LPS 处理的小鼠海马神经元丧失

IF 4.2 3区医学

Journal of Neuroscience Research Pub Date : 2024-04-24 DOI: 10.1002/jnr.25336

Luis A. Rojas-Colón, John B. Redell, Pramod K. Dash, Pedro E. Vegas, Wanda Vélez-Torres

{"title":"4R-cembranoid suppresses glial cells inflammatory phenotypes and prevents hippocampal neuronal loss in LPS-treated mice","authors":"Luis A. Rojas-Colón, John B. Redell, Pramod K. Dash, Pedro E. Vegas, Wanda Vélez-Torres","doi":"10.1002/jnr.25336","DOIUrl":"https://doi.org/10.1002/jnr.25336","url":null,"abstract":"Chronic neuroinflammation has been implicated in neurodegenerative disease pathogenesis. A key feature of neuroinflammation is neuronal loss and glial activation, including microglia and astrocytes. 4R-cembranoid (4R) is a natural compound that inhibits hippocampal pro-inflammatory cytokines and increases memory function in mice. We used the lipopolysaccharide (LPS) injection model to study the effect of 4R on neuronal density and microglia and astrocyte activation. C57BL/6J wild-type mice were injected with LPS (5 mg/kg) and 2 h later received either 4R (6 mg/kg) or vehicle. Mice were sacrificed after 72 h for analysis of brain pathology. Confocal images of brain sections immunostained for microglial, astrocyte, and neuronal markers were used to quantify cellular hippocampal phenotypes and neurons. Hippocampal lysates were used to measure the expression levels of neuronal nuclear protein (NeuN), inducible nitrous oxide synthase (iNOS), arginase-1, thrombospondin-1 (THBS1), glial cell-derived neurotrophic factor (GDNF), and orosomucoid-2 (ORM2) by western blot. iNOS and arginase-1 are widely used protein markers of pro- and anti-inflammatory microglia, respectively. GDNF promotes neuronal survival, and ORM2 and THBS1 are astrocytic proteins that regulate synaptic plasticity and inhibit microglial activation. 4R administration significantly reduced neuronal loss and the number of pro-inflammatory microglia 72 h after LPS injection. It also decreased the expression of the pro-inflammatory protein iNOS while increasing arginase-1 expression, supporting its anti-inflammatory role. The protein expression of THBS1, GDNF, and ORM2 was increased by 4R. Our data show that 4R preserves the integrity of hippocampal neurons against LPS-induced neuroinflammation in mice.","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"102 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jnr.25336","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140639592","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}

引用次数: 0

Mismatch novelty exploration training shifts VPAC1 receptor-mediated modulation of hippocampal synaptic plasticity by endogenous VIP in male rats 错配新奇探索训练改变了雄性大鼠 VPAC1 受体介导的内源性 VIP 对海马突触可塑性的调节作用

IF 4.2 3区医学

Journal of Neuroscience Research Pub Date : 2024-04-24 DOI: 10.1002/jnr.25333

Fatima Aidil-Carvalho, Ana Caulino-Rocha, Joaquim Alexandre Ribeiro, Diana Cunha-Reis

{"title":"Mismatch novelty exploration training shifts VPAC1 receptor-mediated modulation of hippocampal synaptic plasticity by endogenous VIP in male rats","authors":"Fatima Aidil-Carvalho, Ana Caulino-Rocha, Joaquim Alexandre Ribeiro, Diana Cunha-Reis","doi":"10.1002/jnr.25333","DOIUrl":"https://doi.org/10.1002/jnr.25333","url":null,"abstract":"Novelty influences hippocampal-dependent memory through metaplasticity. Mismatch novelty detection activates the human hippocampal CA1 area and enhances rat hippocampal-dependent learning and exploration. Remarkably, mismatch novelty training (NT) also enhances rodent hippocampal synaptic plasticity while inhibition of VIP interneurons promotes rodent exploration. Since VIP, acting on VPAC1 receptors (Rs), restrains hippocampal LTP and depotentiation by modulating disinhibition, we now investigated the impact of NT on VPAC1 modulation of hippocampal synaptic plasticity in male Wistar rats. NT enhanced both CA1 hippocampal LTP and depotentiation unlike exploring an empty holeboard (HT) or a fixed configuration of objects (FT). Blocking VIP VPAC1Rs with PG 97269 (100 nM) enhanced both LTP and depotentiation in naïve animals, but this effect was less effective in NT rats. Altered endogenous VIP modulation of LTP was absent in animals exposed to the empty environment (HT). HT and FT animals showed mildly enhanced synaptic VPAC1R levels, but neither VIP nor VPAC1R levels were altered in NT animals. Conversely, NT enhanced the GluA1/GluA2 AMPAR ratio and gephyrin synaptic content but not PSD-95 excitatory synaptic marker. In conclusion, NT influences hippocampal synaptic plasticity by reshaping brain circuits modulating disinhibition and its control by VIP-expressing hippocampal interneurons while upregulation of VIP VPAC1Rs is associated with the maintenance of VIP control of LTP in FT and HT animals. This suggests VIP receptor ligands may be relevant to co-adjuvate cognitive recovery therapies in aging or epilepsy, where LTP/LTD imbalance occurs.","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"102 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jnr.25333","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140639590","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}

引用次数: 0

Iron deficiency in astrocytes alters cellular status and impacts on oligodendrocyte differentiation 星形胶质细胞缺铁会改变细胞状态并影响少突胶质细胞的分化

IF 4.2 3区医学

Journal of Neuroscience Research Pub Date : 2024-04-24 DOI: 10.1002/jnr.25334

María Silvina Marcora, Vanesa Soledad Mattera, Pilar Goñi, Florencia Aybar, Jorge Daniel Correale, Juana Maria Pasquini

{"title":"Iron deficiency in astrocytes alters cellular status and impacts on oligodendrocyte differentiation","authors":"María Silvina Marcora, Vanesa Soledad Mattera, Pilar Goñi, Florencia Aybar, Jorge Daniel Correale, Juana Maria Pasquini","doi":"10.1002/jnr.25334","DOIUrl":"https://doi.org/10.1002/jnr.25334","url":null,"abstract":"Iron deficiency (ID) has been shown to affect central nervous system (CNS) development and induce hypomyelination. Previous work from our laboratory in a gestational ID model showed that both oligodendrocyte (OLG) and astrocyte (AST) maturation was impaired. To explore the contribution of AST iron to the myelination process, we generated an in vitro ID model by silencing divalent metal transporter 1 (DMT1) in AST (siDMT1 AST) or treating AST with Fe3+ chelator deferoxamine (DFX; DFX AST). siDMT1 AST showed no changes in proliferation but remained immature. Co-cultures of oligodendrocyte precursors cells (OPC) with siDMT1 AST and OPC cultures incubated with siDMT1 AST-conditioned media (ACM) rendered a reduction in OPC maturation. These findings correlated with a decrease in the expression of AST-secreted factors IGF-1, NRG-1, and LIF, known to promote OPC differentiation. siDMT1 AST also displayed increased mitochondrial number and reduced mitochondrial size as compared to control cells. DFX AST also remained immature and DFX AST-conditioned media also hampered OPC maturation in culture, in keeping with a decrease in the expression of AST-secreted growth factors IGF-1, NRG-1, LIF, and CNTF. DFX AST mitochondrial morphology and number showed results similar to those observed in siDMT1 AST. In sum, our results show that ID, induced through two different methods, impacts AST maturation and mitochondrial functioning, which in turn hampers OPC differentiation.","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"102 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140639591","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}

引用次数: 0

Increased glutamatergic neurotransmission between the retinohypothalamic tract and the suprachiasmatic nucleus of old mice 老龄小鼠视网膜下丘脑束和丘脑上核之间的谷氨酸能神经传递增加

IF 4.2 3区医学

Journal of Neuroscience Research Pub Date : 2024-04-23 DOI: 10.1002/jnr.25331

J. Manuel Herrera-Zamora, Fernando Osuna-Lopez, Miriam E. Reyes-Méndez, Ramon E. Valadez-Lemus, Enrique A. Sánchez-Pastor, Ricardo A. Navarro-Polanco, Eloy G. Moreno-Galindo, Javier Alamilla

{"title":"Increased glutamatergic neurotransmission between the retinohypothalamic tract and the suprachiasmatic nucleus of old mice","authors":"J. Manuel Herrera-Zamora, Fernando Osuna-Lopez, Miriam E. Reyes-Méndez, Ramon E. Valadez-Lemus, Enrique A. Sánchez-Pastor, Ricardo A. Navarro-Polanco, Eloy G. Moreno-Galindo, Javier Alamilla","doi":"10.1002/jnr.25331","DOIUrl":"https://doi.org/10.1002/jnr.25331","url":null,"abstract":"Circadian rhythms synchronize to light through the retinohypothalamic tract (RHT), which is a bundle of axons coming from melanopsin retinal ganglion cells, whose synaptic terminals release glutamate to the ventral suprachiasmatic nucleus (SCN). Activation of AMPA–kainate and NMDA postsynaptic receptors elicits the increase in intracellular calcium required for triggering the signaling cascade that ends in phase shifts. During aging, there is a decline in the synchronization of circadian rhythms to light. With electrophysiological (whole-cell patch-clamp) and immunohistochemical assays, in this work, we studied pre- and postsynaptic properties between the RHT and ventral SCN neurons in young adult (P90–120) and old (P540–650) C57BL/6J mice. Incremental stimulation intensities (applied on the optic chiasm) induced much lesser AMPA–kainate postsynaptic responses in old animals, implying a lower recruitment of RHT fibers. Conversely, a higher proportion of old SCN neurons exhibited synaptic facilitation, and variance–mean analysis indicated an increase in the probability of release in RHT terminals. Moreover, both spontaneous and miniature postsynaptic events displayed larger amplitudes in neurons from aged mice, whereas analysis of the NMDA and AMPA–kainate components (evoked by RHT electrical stimulation) disclosed no difference between the two ages studied. Immunohistochemistry revealed a bigger size in the puncta of vGluT2, GluN2B, and GluN2A of elderly animals, and the number of immunopositive particles was increased, but that of PSD-95 was reduced. All these synaptic adaptations could be part of compensatory mechanisms in the glutamatergic signaling to ameliorate the loss of RHT terminals in old animals.","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"102 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140633830","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}

引用次数: 0