Current research in neurobiology最新文献

{"title":"Altered pattern separation in Goto-Kakizaki rats","authors":"Chelsey C. Damphousse,&nbsp;Jaclyn K. Medeiros,&nbsp;Nicole E. Micks,&nbsp;Diano F. Marrone","doi":"10.1016/j.crneur.2023.100082","DOIUrl":"10.1016/j.crneur.2023.100082","url":null,"abstract":"<div><p>Type 2 diabetes mellitus has steadily increased in prevalence over the past five decades. Among the health risks associated with this disorder are cognitive decline and are increased risk of developing dementia. To further investigate the link between diabetes and cognition, here we test memory performance and hippocampal function in the Goto-Kakizaki (GK) rat, a robust model of diabetes. Relative to age-matched Wistar rats, GK rats show impairments in a conjunctive memory task that requires discriminating objects not only on the basis of their physical characteristics, but also on the basis of where and when they were last seen. Concomitant to these deficits are changes in the pattern of expression of <em>Egr1</em> (an immediate-early gene critical for memory) in dentate gyrus granule cells, consistent with dentate hypoactivity leading to unstable hippocampal representations. These data support the hypothesis that diabetes confers a phenotype of accelerated senescence on the hippocampus, and help to link this disorder with changes in hippocampal circuits.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"4 ","pages":"Article 100082"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10313866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10123129","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}

{"title":"Δ9-Tetrahydrocannabinol does not upregulate an aversive dopamine receptor mechanism in adolescent brain unlike in adults","authors":"Marie-Eve Di Raddo ,&nbsp;Marija Milenkovic ,&nbsp;Meenalochani Sivasubramanian ,&nbsp;Ahmed Hasbi ,&nbsp;Jack Bergman ,&nbsp;Sarah Withey ,&nbsp;Bertha K. Madras ,&nbsp;Susan R. George","doi":"10.1016/j.crneur.2023.100107","DOIUrl":"10.1016/j.crneur.2023.100107","url":null,"abstract":"<div><p>Earlier age of cannabis usage poses higher risk of Cannabis Use Disorder and adverse consequences, such as addiction, anxiety, dysphoria, psychosis, largely attributed to its principal psychoactive component, Δ9-tetrahydrocannabinol (THC) and altered dopaminergic function. As dopamine D1-D2 receptor heteromer activation causes anxiety and anhedonia, this signaling complex was postulated to contribute to THC-induced affective symptoms. To investigate this, we administered THC repeatedly to adolescent monkeys and adolescent or adult rats. Drug-naïve adolescent rat had lower striatal densities of D1-D2 heteromer compared to adult rat. Repeated administration of THC to adolescent rat or adolescent monkey did not alter D1-D2 heteromer expression in nucleus accumbens or dorsal striatum but upregulated it in adult rat. Behaviourally, THC-treated adult, but not adolescent rat manifested anxiety and anhedonia-like behaviour, with elevated composite negative emotionality scores that correlated with striatal D1-D2 density. THC modified downstream markers of D1-D2 activation in adult, but not adolescent striatum. THC administered with cannabidiol did not alter D1-D2 expression. In adult rat, co-administration of CB1 receptor (CB1R) inverse agonist with THC attenuated D1-D2 upregulation, implicating cannabinoids in the regulation of striatal D1-D2 heteromer expression. THC exposure revealed an adaptable age-specific, anxiogenic, anti-reward mechanism operant in adult striatum but deficient in adolescent rat and monkey striatum that may confer increased sensitivity to THC reward in adolescence while limiting its negative effects, thus promoting continued use and increasing vulnerability to long-term adverse cannabis effects.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"5 ","pages":"Article 100107"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44535835","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}

{"title":"From X-inactivation to neurodevelopment: CHD8-transcription factors (TFs) competitive binding at regulatory regions of CHD8 target genes can contribute to correct neuronal differentiation","authors":"Andrea Cerase ,&nbsp;Philip Avner","doi":"10.1016/j.crneur.2023.100114","DOIUrl":"https://doi.org/10.1016/j.crneur.2023.100114","url":null,"abstract":"<div><p>The chromodomain helicase DNA-binding protein 8 (CHD8) is a chromatin remodeler whose mutation is associated, with high penetrance, with autism. Individuals with <em>CHD8</em> mutations share common symptoms such as autistic behaviour, cognitive impairment, schizophrenia comorbidity, and phenotypic features such as macrocephaly and facial defects. <em>Chd8</em>-deficient mouse models recapitulate most of the phenotypes seen in the brain and other organs of humans. It is known that CHD8 regulates - directly and indirectly - neuronal, autism spectrum disorder (ASDs)-associated genes and long non-coding RNAs (lncRNAs) genes, which, in turn, regulate fundamental aspects of neuronal differentiation and brain development and function. A major characteristic of CHD8 regulation of gene expression is its non-linear and dosage-sensitive nature. <em>CHD8</em> mutations appear to affect males predominantly, although the reasons for this observed sex bias remain- unknown. We have recently reported that CHD8 directly regulates X chromosome inactivation (XCI) through the transcriptional control of the Xist long non-coding RNA (lncRNA), the master regulator of mammalian XCI. We identified a role for CHD8 in regulating accessibility at the Xist promoter through competitive binding with transcription factors (TFs) at Xist regulatory regions. We speculate here that CHD8 might also regulate accessibility at neuronal/ASD targets through a similar competitive binding mechanism during neurogenesis and brain development. However, whilst such a model can reconcile the phenotypic differences observed in <em>Chd8</em> knock-down (KD) vs knock-out (KO) mouse models, explaining the observed CHD8 non-linear dosage-dependent activity, it cannot on its own explain the observed disease sex bias.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"5 ","pages":"Article 100114"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665945X23000426/pdfft?md5=13ef71c6395bb4e1a50179e12f9253e7&pid=1-s2.0-S2665945X23000426-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134654037","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}

{"title":"Longitudinal evaluation of the functional connectivity changes in the secondary somatosensory cortex (S2) of the monkey brain during acute stroke","authors":"Chun-Xia Li ,&nbsp;Frank Tong ,&nbsp;Doty Kempf ,&nbsp;Leonard Howell ,&nbsp;Xiaodong Zhang","doi":"10.1016/j.crneur.2023.100097","DOIUrl":"10.1016/j.crneur.2023.100097","url":null,"abstract":"<div><h3>Background</h3><p>Somatosensory deficits are frequently seen in acute stroke patients and may recover over time and affect functional outcome. However, the underlying mechanism of function recovery remains poorly understood. In the present study, progressive function alteration of the secondary somatosensory cortex (S2) and its relationship with regional perfusion and neurological outcome were examined using a monkey model of stroke.</p></div><div><h3>Methods and materials</h3><p>Rhesus monkeys (n = 4) were induced with permanent middle cerebral artery occlusion (pMCAo). Resting-state functional MRI, dynamic susceptibility contrast perfusion MRI, diffusion-weighted, T₁ and T₂ weighted images were collected before surgery and at 4–6, 48, and 96 h post stroke on a 3T scanner. Progressive changes of relative functional connectivity (FC), cerebral blood flow (CBF), and CBF/Tmax (Time to Maximum) of affected S2 regions were evaluated. Neurological deficits were assessed using the Spetzler approach.</p></div><div><h3>Results</h3><p>Ischemic lesion was evidently seen in the MCA territory including S2 in each monkey. Relative FC of injured S2 regions decreased substantially following stroke. Spetzler scores dropped substantially at 24 h post stroke but slightly recovered from Day 2 to Day 4. Relative FC progressively increased from 6 to 48 and 96 h post stroke and correlated significantly with relative CBFand CBF/Tmax changes.</p></div><div><h3>Conclusion</h3><p>The present study revealed the progressive alteration of function connectivity in S2 during acute stroke. The preliminary results suggested the function recovery might start couple days post occlusion and collateral circulation might play a key role in the recovery of somatosensory function after stroke insult. The relative function connectivity in S2 may provide additional information for prediction of functional outcome in stroke patients.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"5 ","pages":"Article 100097"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c5/e7/main.PMC10315998.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9792740","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}

{"title":"Serotonergic mediation of the brain-wide neurogenesis: Region-dependent and receptor-type specific roles on neurogenic cellular transformation","authors":"Yuki Higuchi,&nbsp;Hiroyuki Arakawa","doi":"10.1016/j.crneur.2023.100102","DOIUrl":"10.1016/j.crneur.2023.100102","url":null,"abstract":"<div><p>Brain serotonin (5-hydroxytryptamine, 5-HT) is a key molecule for the mediation of depression-related brain states, but the neural mechanisms underlying 5-HT mediation need further investigation. A possible mechanism of the therapeutic antidepressant effects is neurogenic cell production, as stimulated by 5-HT signaling. Neurogenesis, the proliferation of neural stem cells (NSCs), and cell differentiation and maturation occur across brain regions, particularly the hippocampal dentate gyrus and the subventricular zone, throughout one's lifespan. 5-HT plays a major role in the mediation of neurogenic processes, which in turn leads to the therapeutic effect on depression-related states. In this review article, we aim to identify how the neuronal 5-HT system mediates the process of neurogenesis, including cell proliferation, cell-type differentiation and maturation. First, we will provide an overview of the neurogenic cell transformation that occurs in brain regions containing or lacking NSCs. Second, we will review brain region-specific mechanisms of 5-HT-mediated neurogenesis by comparing regions localized to NSCs, i.e., the hippocampus and subventricular zone, with those not containing NSCs. Highlighting these 5-HT mechanisms that mediate neurogenic cell production processes in a brain-region-specific manner would provide unique insights into the role of 5-HT in neurogenesis and its associated effects on depression.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"5 ","pages":"Article 100102"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10458724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10109824","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}

{"title":"Are musical activities associated with enhanced speech perception in noise in adults? A systematic review and meta-analysis","authors":"Elisabeth Maillard ,&nbsp;Marilyne Joyal ,&nbsp;Micah M. Murray ,&nbsp;Pascale Tremblay","doi":"10.1016/j.crneur.2023.100083","DOIUrl":"10.1016/j.crneur.2023.100083","url":null,"abstract":"<div><p>The ability to process speech in noise (SPiN) declines with age, with a detrimental impact on life quality. Music-making activities such as singing and playing a musical instrument have raised interest as potential prevention strategies for SPiN perception decline because of their positive impact on several brain system, especially the auditory system, which is critical for SPiN. However, the literature on the effect of musicianship on SPiN performance has yielded mixed results. By critically assessing the existing literature with a systematic review and a meta-analysis, we aim to provide a comprehensive portrait of the relationship between music-making activities and SPiN in different experimental conditions. 38/49 articles, most focusing on young adults, were included in the quantitative analysis. The results show a positive relationship between music-making activities and SPiN, with the strongest effects found in the most challenging listening conditions, and little to no effect in less challenging situations. This pattern of results supports the notion of a relative advantage for musicians on SPiN performance and clarify the scope of this effect. However, further studies, especially with older adults, using adequate randomization methods, are needed to extend the present conclusions and assess the potential for musical activities to be used to mitigate SPiN decline in seniors.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"4 ","pages":"Article 100083"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a6/1b/main.PMC10313871.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9745784","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}

{"title":"Methods for shipping live primary cortical and hippocampal neuron cultures from postnatal mice","authors":"Ferass M. Sammoura ,&nbsp;Dina Popova ,&nbsp;Ayeshia Morris ,&nbsp;Ronald P. Hart ,&nbsp;Jason R. Richardson","doi":"10.1016/j.crneur.2022.100069","DOIUrl":"10.1016/j.crneur.2022.100069","url":null,"abstract":"<div><p>Primary neuronal cultures have proven to be a powerful tool for studying mechanisms in neuroscience. It is technically challenging and expensive to reproduce high quality viable neuronal cultures. Laboratories that are not experienced or equipped to prepare primary neuron cultures may have difficulty producing consistent cultures for experiments. It has previously been shown that live rat embryonic hippocampal cultures can be shipped from laboratories that produce them. Here, we show that variations to this procedure allow for shipping postnatal mouse cultures of hippocampal and cortical primary neurons using standard commercial couriers. We also show that after shipping, primary neurons are viable, express synaptic markers, and demonstrate physiological activity, making them relevant models over immortalized cell lines. Among the many applications of this technique would be the preparation of cultured neurons from transgenic mouse lines in one laboratory and sharing them with distant collaborators, reducing variability.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"4 ","pages":"Article 100069"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fb/3e/main.PMC9794877.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10531950","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}

{"title":"The systemic inhibition of the terminal complement system reduces neuroinflammation but does not improve motor function in mouse models of CMT1A with overexpressed PMP22","authors":"Iliana Michailidou ,&nbsp;Jeroen Vreijling ,&nbsp;Matthijs Rumpf ,&nbsp;Maarten Loos ,&nbsp;Bastijn Koopmans ,&nbsp;Nina Vlek ,&nbsp;Nina Straat ,&nbsp;Cedrick Agaser ,&nbsp;Thomas B. Kuipers ,&nbsp;Hailiang Mei ,&nbsp;Frank Baas ,&nbsp;Kees Fluiter","doi":"10.1016/j.crneur.2023.100077","DOIUrl":"https://doi.org/10.1016/j.crneur.2023.100077","url":null,"abstract":"<div><p>Charcot-Marie-Tooth disease type 1A (CMT1A) is the most prevalent hereditary demyelinating neuropathy. This autosomal, dominantly inherited disease is caused by a duplication on chromosome 17p which includes the peripheral myelin protein 22 (PMP22) gene. There is clinical evidence that the disability in CMT1A is to a large extend due to axonal damage rather than demyelination. Over-expression of <em>PMP22</em> is recently thought to impede cholesterol trafficking causing a total shutdown of local cholesterol and lipid synthesis in the Schwann cells, thus disturbing their ability to remyelinate. But there is a large variety in disease burden between CMT1A patients with the same genetic defect, indicating the presence of modifying factors that affect disease severity. One of these potential factors is the immune system. Several reports have described patients with co-occurrence of CMT1A with chronic inflammatory demyelinating disease or Guillain-Barré syndrome. We have previously shown in multiple animal models that the innate immune system and specifically the terminal complement system is a driver of inflammatory demyelination. To test the contribution of the terminal complement system to neuroinflammation and disease progression in CMT1A, we inhibited systemic complement C6 in two transgenic mouse models for CMT1A, the C3-<em>PMP22</em> and C3-<em>PMP22</em> c-JunP0Cre models. Both models over-express human <em>PMP22</em>, and one (C3-<em>PMP22</em> c-JunP0Cre) also has a Schwann cell-specific knockout of c-Jun, a crucial regulator of myelination controlling autophagy. We found that systemic inhibition of C6 using antisense oligonucleotides affects the neuroinflammation, Rho GTPase and ERK/MAPK signalling pathways in the CMT1A mouse models. The cholesterol synthesis pathway remained unaffected. Analysis of motor function during treatment with C6 antisense oligonucleotides did not reveal any significant improvement in the CMT1A mouse models. This study shows that the contribution of the terminal complement system to progressive loss of motor function in the CMT1A mouse models tested is limited.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"4 ","pages":"Article 100077"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49774897","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}

{"title":"Advances in AAV technology for delivering genetically encoded cargo to the nonhuman primate nervous system","authors":"Lillian J. Campos ,&nbsp;Cynthia M. Arokiaraj ,&nbsp;Miguel R. Chuapoco ,&nbsp;Xinhong Chen ,&nbsp;Nick Goeden ,&nbsp;Viviana Gradinaru ,&nbsp;Andrew S. Fox","doi":"10.1016/j.crneur.2023.100086","DOIUrl":"10.1016/j.crneur.2023.100086","url":null,"abstract":"<div><p>Modern neuroscience approaches including optogenetics, calcium imaging, and other genetic manipulations have facilitated our ability to dissect specific circuits in rodent models to study their role in neurological disease. These approaches regularly use viral vectors to deliver genetic cargo (e.g., opsins) to specific tissues and genetically-engineered rodents to achieve cell-type specificity. However, the translatability of these rodent models, cross-species validation of identified targets, and translational efficacy of potential therapeutics in larger animal models like nonhuman primates remains difficult due to the lack of efficient primate viral vectors. A refined understanding of the nonhuman primate nervous system promises to deliver insights that can guide the development of treatments for neurological and neurodegenerative diseases. Here, we outline recent advances in the development of adeno-associated viral vectors for optimized use in nonhuman primates. These tools promise to help open new avenues for study in translational neuroscience and further our understanding of the primate brain.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"4 ","pages":"Article 100086"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10313870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9745781","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}

{"title":"Maresin-2 inhibits inflammatory and neuropathic trigeminal pain and reduces neuronal activation in the trigeminal ganglion","authors":"Raphael Vieira Lopes ,&nbsp;Darciane Favero Baggio ,&nbsp;Camila Rodrigues Ferraz ,&nbsp;Mariana Marques Bertozzi ,&nbsp;Telma Saraiva-Santos ,&nbsp;Waldiceu Aparecido Verri Junior ,&nbsp;Juliana Geremias Chichorro","doi":"10.1016/j.crneur.2023.100093","DOIUrl":"10.1016/j.crneur.2023.100093","url":null,"abstract":"<div><p>Pain is a common symptom associated with disorders involving the orofacial structures. Most acute orofacial painful conditions are easily recognized, but the pharmacological treatment may be limited by the adverse events of current available drugs and/or patients’ characteristics. In addition, chronic orofacial pain conditions represent clinical challenges both, in terms of diagnostic and treatment. There is growing evidence that specialized pro-resolution lipid mediators (SPMs) present potent analgesic effects, in addition to their well characterized role in the resolution of inflammation. Maresins (MaR-1 and MaR-2) were the last described members of this family, and MaR-2 analgesic action has not yet been reported. Herein the effect of MaR-2 in different orofacial pain models was investigated. MaR-2 (1 or 10 ng) was always delivered via medullary subarachnoid injection, which corresponds to the intrathecal treatment. A single injection of MaR-2 caused a significant reduction of phases I and II of the orofacial formalin test in rats. Repeated injections of MaR-2 prevented the development of facial heat and mechanical hyperalgesia in a model of post-operative pain in rats. In a model of trigeminal neuropathic pain (CCI-ION), repeated MaR-2 injections reversed facial heat and mechanical hyperalgesia in rats and mice. CCI-ION increased c-Fos positive neurons and CGRP⁺ activated (nuclear pNFkB) neurons in the trigeminal ganglion (TG), which were restored to sham levels by MaR-2 repeated treatment. In conclusion, MaR-2 showed potent and long-lasting analgesic effects in inflammatory and neuropathic pain of orofacial origin and the inhibition of CGRP-positive neurons in the TG may account for MaR-2 action.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"4 ","pages":"Article 100093"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/25/2c/main.PMC10313899.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10123128","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}