Neurochemistry international最新文献

{"title":"The developing mouse dopaminergic system: Cortical-subcortical shift in D1/D2 receptor balance and increasing regional differentiation","authors":"Ingvild E. Bjerke ,&nbsp;Harry Carey ,&nbsp;Jan G. Bjaalie ,&nbsp;Trygve B. Leergaard ,&nbsp;Jee Hyun Kim","doi":"10.1016/j.neuint.2024.105899","DOIUrl":"10.1016/j.neuint.2024.105899","url":null,"abstract":"<div><div>The dopaminergic system of the brain is involved in complex cognitive functioning and undergoes extensive reorganization during development. Yet, these changes are poorly characterized. We have quantified the density of dopamine 1- and 2-receptor (D1 and D2) positive cells across the forebrain of male and female mice at five developmental stages using validated transgenic mice expressing green fluorescent protein in cells producing D1 or D2 mRNA. After analyzing &gt;4,500 coronal brain images, a cortico-subcortical shift in D1/D2 balance was discovered, with increasing D1 dominance in cortical regions as a maturational pattern that occurs earlier in females. We describe postnatal trajectories of D1 and D2 cell densities across major brain regions and observe increasing regional differentiation of D1 densities through development. Our results provide the most comprehensive overview of the developing dopaminergic system to date, and an empirical foundation for further experimental and computational investigations of dopaminergic signaling.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"182 ","pages":"Article 105899"},"PeriodicalIF":4.4,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611482","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":"An overview of the relationship between inflammation and cognitive function in humans, molecular pathways and the impact of nutraceuticals","authors":"Chusana Mekhora ,&nbsp;Daniel J. Lamport ,&nbsp;Jeremy P.E. Spencer","doi":"10.1016/j.neuint.2024.105900","DOIUrl":"10.1016/j.neuint.2024.105900","url":null,"abstract":"<div><div>Inflammation has been associated with cognitive decline, whether in the peripheral or central nervous systems. The primary mechanism involves the response of microglia, an immune cell in the brain, which generates pro-inflammatory mediators such as cytokines, chemokines, and adhesion molecules. The excessive production of pro-inflammatory mediators may accelerate the damage to neurons, contributing to the development of neurodegenerative diseases such as Alzheimer's disease, mild cognitive impairment, and vascular dementia, as well as a general decline in cognitive function. Various studies have supported the correlation between elevated pro-inflammatory mediators and a decline in cognitive function, particularly in aging and age-related neurodegenerative diseases. Moreover, this association has also been observed in other inflammatory-related conditions, including post-operative cognitive impairment, diabetes, stroke, obesity, and cancer. However, the interaction between inflammatory processes and cognitive function in humans remains unclear and varies according to different health conditions. Therefore, this review aims to consolidate and evaluate the available evidence from original studies as well as meta-analyses in order to provide a greater understanding of the inflammatory process in connection with cognitive function in humans. Furthermore, relevant biological cellular processes, putative inflammatory biomarkers, and the role of nutraceuticals on the interaction between cognitive performance and inflammatory status are outlined.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"181 ","pages":"Article 105900"},"PeriodicalIF":4.4,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611486","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":"Impairment of neuromotor development and cognition associated with histopathological and neurochemical abnormalities in the cerebral cortex and striatum of glutaryl-CoA dehydrogenase deficient mice","authors":"Ediandra Tissot Castro ,&nbsp;Rafael Teixeira Ribeiro ,&nbsp;Andrey Vinicios Soares Carvalho ,&nbsp;Diorlon Nunes Machado ,&nbsp;Ângela Beatris Zemniaçak ,&nbsp;Rafael Palavro ,&nbsp;Sâmela de Azevedo Cunha ,&nbsp;Tailine Quevedo Tavares ,&nbsp;Diogo Onofre Gomes de Souza ,&nbsp;Carlos Alexandre Netto ,&nbsp;Guilhian Leipnitz ,&nbsp;Alexandre Umpierrez Amaral ,&nbsp;Moacir Wajner","doi":"10.1016/j.neuint.2024.105898","DOIUrl":"10.1016/j.neuint.2024.105898","url":null,"abstract":"<div><div>Patients with glutaric acidemia type I (GA I) manifest motor and intellectual disabilities whose pathogenesis has been so far poorly explored. Therefore, we evaluated neuromotor and cognitive abilities, as well as histopathological and immunohistochemical features in the cerebral cortex and striatum of glutaryl-CoA dehydrogenase (GCDH) deficient knockout mice (<em>Gcdh</em>^{<em>−/−</em>}), a well-recognized model of GA I. The effects of a single intracerebroventricular glutaric acid (GA) injection in one-day-old pups on the same neurobehavioral and histopathological/immunohistochemical endpoints were also investigated. Seven-day-old <em>Gcdh</em>^{<em>−/−</em>} mice presented altered gait, whereas those receiving a GA neonatal administration manifested other sensorimotor deficits, including an abnormal response to negative geotaxis, cliff aversion and righting reflex, and muscle tone impairment. Compared to the WT mice, adult <em>Gcdh−/−</em> mice exhibited motor impairment, evidenced by poor performance in the Rota-rod test. Furthermore, neonatal GA administration provoked long-standing short- and long-term memory impairment in adult <em>Gcdh</em>^{<em>−/−</em>} mice. Regarding the histopathological features, a significant increase in vacuoles and neurodegenerative cells was observed in both the cerebral cortex and striatum of 15- and 60-day-old Gcd<em>h−/−</em> mice and was more pronounced in mice injected with GA. Neuronal loss (decrease of NeuN staining) was also significantly increased in the cerebral cortex and striatum of <em>Gcdh</em>^{<em>−/−</em>} mice, particularly in those neonatally injected with GA. In contrast, immunohistochemistry of MBP, astrocytic proteins GFAP and S100B, and the microglial marker Iba1 was not changed in 60-day-old Gcdh−/− mice, suggesting no myelination disturbance, reactive astrogliosis, and microglia activation, respectively. These data highlight the neurotoxicity of GA and the importance of early treatment aiming to decrease GA accumulation at early stages of development to prevent brain damage and learning/memory disabilities in GA I patients.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"181 ","pages":"Article 105898"},"PeriodicalIF":4.4,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611499","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":"Boron: An intriguing factor in retarding Alzheimer's progression","authors":"Ashmita Das ,&nbsp;Vikas Rajput ,&nbsp;Durlav Chowdhury ,&nbsp;Rajesh Choudhary ,&nbsp;Surendra H. Bodakhe","doi":"10.1016/j.neuint.2024.105897","DOIUrl":"10.1016/j.neuint.2024.105897","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is a neurodegenerative disorder that is the fifth most common cause of mortality worldwide and the second most common cause of death in developed countries. The etiology of AD remains poorly understood; however, it is correlated with the accumulation of proteins in the brain, ultimately leading to cellular damage. Multiple factors, including genetic and environmental factors such as chemicals or food, have been linked to protein aggregation and cell death in AD. Boron is a vital micronutrient that is necessary for plant growth and is abundantly present in various fruits and nuts. Prior research has emphasized the importance of boron as a neuroprotective agent and necessary component for the preservation of brain health and function. However, the precise function of boron in the brain remains poorly understood. This review elucidates the molecular role of boron in the brain by examining existing information about its impact on neurodegenerative diseases and may provide a deeper understanding of the etiology of AD and, ultimately, lead to the development of novel approaches for its treatment.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"181 ","pages":"Article 105897"},"PeriodicalIF":4.4,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611497","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":"Neuroprotective and anti-inflammatory effects of the RIPK3 inhibitor GSK872 in an MPTP-induced mouse model of Parkinson's disease","authors":"Jin-Sun Park ,&nbsp;Yea-Hyun Leem ,&nbsp;Do-Yeon Kim ,&nbsp;Jae-Min Park ,&nbsp;Seong-Eun Kim ,&nbsp;Hee-Sun Kim","doi":"10.1016/j.neuint.2024.105896","DOIUrl":"10.1016/j.neuint.2024.105896","url":null,"abstract":"<div><div>Parkinson's disease (PD) is a neurodegenerative disorder triggered by the loss of dopaminergic neurons in the substantia nigra (SN). Recent studies have demonstrated that necroptosis is involved in dopaminergic neuronal cell death and the resulting neuroinflammation. During the process of necroptosis, a necrosome complex is formed consisting of the proteins receptor-interacting protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like protein (MLKL). Although the neuroprotective effects of the RIPK1-specific inhibitor necrostatin-1, as well as RIPK3 and MLKL knockout in mice, have been described, the effects of RIPK3 pharmacological inhibitors have not yet been reported in animal models of PD. In the present study, we investigated the neuroprotective effects of GSK872, a specific RIPK3 inhibitor, in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. GSK872 rescued MPTP-induced motor impairment and inhibited tyrosine hydroxylase-positive dopaminergic cell death in the SN and striatum. Additionally, GSK872 inhibited the MPTP-induced increase in the expression of <em>p</em>-RIPK3 and <em>p</em>-MLKL in both the dopaminergic neurons and microglia, as assessed by biochemical and histological analyses. GSK872 further inhibited microglial activation and the expression of inflammatory mediators including NLRP3, interleukin (IL)-1β, IL-6, tumor necrosis factor-alpha, and inducible nitric oxide synthase in the SN region of MPTP mice. Using in vitro experiments, we validated the effects of GSK872 on necroptosis in SH-SY5Y neuronal and BV2 microglial cells. Overall, our results suggest that GSK872 exerts neuroprotective and anti-inflammatory effects, and may thus have therapeutic potential for PD.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"181 ","pages":"Article 105896"},"PeriodicalIF":4.4,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566765","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":"Altered sex differences related to food intake, hedonic preference, and FosB/deltaFosB expression within central neural circuit involved in homeostatic and hedonic food intake regulation in Shank3B mouse model of autism spectrum disorder","authors":"Zdenko Pirník ,&nbsp;Ivan Szadvári ,&nbsp;Veronika Borbélyová ,&nbsp;Aleksandra Tomova","doi":"10.1016/j.neuint.2024.105895","DOIUrl":"10.1016/j.neuint.2024.105895","url":null,"abstract":"<div><div>Autism spectrum disorder (ASD) is a neurodevelopmental disorder accompanied by narrow interests, difficulties in communication and social interaction, and repetitive behavior. In addition, ASD is frequently associated with eating and feeding problems. Although the symptoms of ASD are more likely to be observed in boys, the prevalence of eating disorders is more common in females. The ingestive behavior is regulated by the integrative system of the brain, which involves both homeostatic and hedonic neural circuits. Sex differences in the physiology of food intake depend on sex hormones regulating the expression of the ASD-associated Shank genes. Shank3 mutation leads to ASD-like traits and Shank3B −/− mice have been established as an animal model to study the neurobiology of ASD. Therefore, the long-lasting neuronal activity in the central neural circuit related to the homeostatic and hedonic regulation of food intake was evaluated in both sexes of Shank3B mice, followed by the evaluation of the food intake and preference. In the Shank3B +/+ genotype, well-preserved relationships in the tonic activity within the homeostatic neural network together with the relationships between ingestion and hedonic preference were observed in males but were reduced in females. These interrelations were partially or completely lost in the mice with the Shank3B −/− genotype. A decreased hedonic preference for the sweet taste but increased total food intake was found in the Shank3B −/− mice. In the Shank3B −/− group, there were altered sex differences related to the amount of tonic cell activity in the hedonic and homeostatic neural networks, together with altered sex differences in sweet and sweet-fat solution intake. Furthermore, the Shank3B −/− females exhibited an increased intake and preference for cheese compared to the Shank3B +/+ ones. The obtained data indicate altered functional crosstalk between the central homeostatic and hedonic neural circuits involved in the regulation of food intake in ASD.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"181 ","pages":"Article 105895"},"PeriodicalIF":4.4,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492290","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":"Discriminating fingerprints of chronic neuropathic pain following spinal cord injury using artificial neural networks and mass spectrometry analysis of female mice serum","authors":"Meritxell Deulofeu ,&nbsp;Eladia M. Peña-Méndez ,&nbsp;Petr Vaňhara ,&nbsp;Josef Havel ,&nbsp;Lukáš Moráň ,&nbsp;Lukáš Pečinka ,&nbsp;Anna Bagó-Mas ,&nbsp;Enrique Verdú ,&nbsp;Victoria Salvadó ,&nbsp;Pere Boadas-Vaello","doi":"10.1016/j.neuint.2024.105890","DOIUrl":"10.1016/j.neuint.2024.105890","url":null,"abstract":"<div><div>Spinal cord injury (SCI) often leads to central neuropathic pain, a condition associated with significant morbidity and is challenging in terms of the clinical management. Despite extensive efforts, identifying effective biomarkers for neuropathic pain remains elusive. Here we propose a novel approach combining matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) with artificial neural networks (ANNs) to discriminate between mass spectral profiles associated with chronic neuropathic pain induced by SCI in female mice. Functional evaluations revealed persistent chronic neuropathic pain following mild SCI as well as minor locomotor disruptions, confirming the value of collecting serum samples. Mass spectra analysis revealed distinct profiles between chronic SCI and sham controls. On applying ANNs, 100% success was achieved in distinguishing between the two groups through the intensities of m/z peaks. Additionally, the ANNs also successfully discriminated between chronic and acute SCI phases. When reflexive pain response data was integrated with mass spectra, there was no improvement in the classification. These findings offer insights into neuropathic pain pathophysiology and underscore the potential of MALDI-TOF MS coupled with ANNs as a diagnostic tool for chronic neuropathic pain, potentially guiding attempts to discover biomarkers and develop treatments.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"181 ","pages":"Article 105890"},"PeriodicalIF":4.4,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492291","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":"Neuron-selective and activity-dependent splicing of BDNF exon I–IX pre-mRNA","authors":"Mamoru Fukuchi ,&nbsp;Yumi Shibasaki ,&nbsp;Yuto Akazawa ,&nbsp;Hitoshi Suzuki-Masuyama ,&nbsp;Ken-ichi Takeuchi ,&nbsp;Yumika Iwazaki ,&nbsp;Akiko Tabuchi ,&nbsp;Masaaki Tsuda","doi":"10.1016/j.neuint.2024.105889","DOIUrl":"10.1016/j.neuint.2024.105889","url":null,"abstract":"<div><div>Brain-derived neurotrophic factor (BDNF) is essential for numerous neuronal functions, including learning and memory. The expression of BDNF is regulated by distinctive transcriptional and post-transcriptional mechanisms. The <em>Bdnf</em> gene in mice and rats comprises eight untranslated exons (exons I–VIII) and one exon (exon IX) that contains the pre-proBDNF coding sequence. Multiple splice donor sites on the untranslated exons and a single acceptor site upstream of the coding sequence result in the characteristic exon skipping patterns that generate multiple <em>Bdnf</em> mRNA variants, which are essential for the spatiotemporal regulation of BDNF expression, mRNA localization, mRNA stability, and translational control. However, the regulation of <em>Bdnf</em> pre-mRNA splicing remains unclear. Here, we focused on the splicing of <em>Bdnf</em> exon I–IX pre-mRNA. We first constructed a minigene to evaluate <em>Bdnf</em> exon I–IX pre-mRNA splicing. Compared with <em>Bdnf</em> exon I–IX pre-mRNA splicing in non-neuronal NIH3T3 cells, splicing was preferentially observed in primary cultures of cortical neurons. Additionally, a series of overexpression and knockdown experiments suggested that neuro-oncological ventral antigen (NOVA) 2 is involved in the neuron-selective splicing of <em>Bdnf</em> exon I–IX pre-mRNA. Supporting this finding, endogenous <em>Nova2</em> mRNA expression was markedly higher in neurons, and a strong correlation between endogenous <em>Bdnf</em> exon I–IX and <em>Nova2</em> mRNA was observed across several brain regions. Furthermore, <em>Bdnf</em> exon I–IX pre-mRNA splicing was facilitated by Ca²⁺ signals evoked via L-type voltage-dependent Ca²⁺ channels. Notably, among the <em>Bdnf</em> pre-mRNA splicing investigated in the current study, neuron-selective and activity-dependent splicing was observed in <em>Bdnf</em> exon I–IX pre-mRNA. In conclusion, <em>Bdnf</em> exon I-IX pre-mRNA splicing is preferentially observed in neurons and is facilitated in an activity-dependent manner. The neuron-selective and activity-dependent splicing of <em>Bdnf</em> exon I–IX pre-mRNA may contribute to the efficient induction of <em>Bdnf</em> exon I–IX expression in neurons.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"181 ","pages":"Article 105889"},"PeriodicalIF":4.4,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492301","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":"Supplemental oxygen alters the pentose phosphate pathway in the developing mouse brain through SIRT signaling","authors":"Defne Engur ,&nbsp;Serap Cilaker Micili ,&nbsp;Sila Soy ,&nbsp;Gökcen Bilici ,&nbsp;Kemal Ugur Tufekci ,&nbsp;Cagla Kiser ,&nbsp;İlkcan Ercan ,&nbsp;Abdullah Kumral ,&nbsp;Sermin Genc","doi":"10.1016/j.neuint.2024.105886","DOIUrl":"10.1016/j.neuint.2024.105886","url":null,"abstract":"<div><div>Oxygen support plays a critical role in the management of preterm infants in neonatal intensive care units. On the other hand, the possible effects of oxygen supplementation on cellular functions, specifically glucose metabolism, have been less understood.</div></div><div><h3>Purpose</h3><div>of the study is to investigate whether supplemental oxygen alters glucose metabolism and pentose phosphate pathway (PPP) activity in the brain tissue and its relevance with silent information regulator proteins (SIRT) pathway. For this purpose, newborn C57BL/6 pups were exposed to 90% oxygen from birth until postnatal day 7 (PN7) and metabolites of glysolysis and PPP were investigated through metabolomics analysis. SIRT1, glucose-6-phosphate dehydrogenase (G6PD) and transaldolase (TALDO) proteins were examined immunohistochemically and molecularly in the prefrontal and hippocampus regions of the brain. Later on, SIRT1 inhibition was carried out.</div><div>Our results indicate that supplemental oxygen causes an increase in PPP metabolites as well as activation of G6PD enzyme in the brain tissue, which is reversed by SIRT1 inhibition. Our study underlines a connection between supplemental oxygen, glucose metabolism, PPP pathway and the SIRT signaling. Understanding these intricate relationships not only deepens our knowledge of cellular physiology but also holds promise for therapeutic interventions for creating neuroprotective strategies in preterm brain.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"180 ","pages":"Article 105886"},"PeriodicalIF":4.4,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492302","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":"Reassessment of capsaicin desensitization in the rodent spinal dorsal horn","authors":"Caifeng Shao ,&nbsp;Wen-Qian Zhou ,&nbsp;Hong-Yi Jia ,&nbsp;Guangying Li ,&nbsp;Yifei Ma ,&nbsp;Mingwei Zhao ,&nbsp;Hongjie Wu ,&nbsp;Kun Yang ,&nbsp;Xin Qian ,&nbsp;Ming-Ming Zhang","doi":"10.1016/j.neuint.2024.105887","DOIUrl":"10.1016/j.neuint.2024.105887","url":null,"abstract":"<div><div>Capsaicin activates primary afferent transient receptor potential vanilloid 1 (TRPV1) in the spinal dorsal horn and induces exaggerated glutamate release. This capsaicin action is followed by a lasting refractory state referred to as “capsaicin desensitization”, which is considered a presynaptic event. In this study, using whole-cell recordings and holographic photostimulation, we reassessed this notion by investigating presynaptic glutamate release and the postsynaptic glutamate response during capsaicin administration. We found that both presynaptic synchronous glutamate release and the postsynaptic glutamate response were largely attenuated in this refractory state; in contrast, asynchronous release was exaggerated. Further behavioral studies revealed a quick increase in the mechanical pain threshold with intrathecal capsaicin administration. Taken together, both presynaptic synchronous glutamate release and the postsynaptic response are downregulated during capsaicin desensitization, and this desensitization may transiently increase the pain threshold. Since both presynaptic synchronous release and postsynaptic glutamate responses are attenuated, the traditional electrophysiological evidence supporting capsaicin desensitization as a presynaptic event should be reassessed.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"181 ","pages":"Article 105887"},"PeriodicalIF":4.4,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492303","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}