Current research in neurobiology最新文献

{"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}

{"title":"Motion distractors perturb saccade programming later in time than static distractors","authors":"Devin H. Kehoe ,&nbsp;Lukas Schießer ,&nbsp;Hassaan Malik ,&nbsp;Mazyar Fallah","doi":"10.1016/j.crneur.2023.100092","DOIUrl":"10.1016/j.crneur.2023.100092","url":null,"abstract":"<div><p>The mechanism that reweights oculomotor vectors based on visual features is unclear. However, the latency of oculomotor visual activations gives insight into their antecedent featural processing. We compared the oculomotor processing time course of grayscale, task-irrelevant static and motion distractors during target selection by continuously measuring a battery of human saccadic behavioral metrics as a function of time after distractor onset. The motion direction was towards or away from the target and the motion speed was fast or slow. We compared static and motion distractors and observed that both distractors elicited curved saccades and shifted endpoints at short latencies (∼25 ms). After 50 ms, saccade trajectory biasing elicited by motion distractors lagged static distractor trajectory biasing by 10 ms. There were no such latency differences between distractor motion directions or motion speeds. This pattern suggests that additional processing of motion stimuli occurred prior to the propagation of visual information into the oculomotor system. We examined the interaction of distractor processing time (DPT) with two additional factors: saccadic reaction time (SRT) and saccadic amplitude. Shorter SRTs were associated with shorter DPT latencies of biased saccade trajectories. Both SRT and saccadic amplitude were associated with the magnitude of saccade trajectory biases.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"4 ","pages":"Article 100092"},"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/95/7d/main.PMC10313862.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9745782","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":"Rb deficiency, neuronal survival and neurodegeneration: In search of the perfect mouse model","authors":"Saad Omais,&nbsp;Yara E. El Atie,&nbsp;Noël Ghanem","doi":"10.1016/j.crneur.2023.100074","DOIUrl":"10.1016/j.crneur.2023.100074","url":null,"abstract":"<div><p>Three decades following the introduction of the first Rb knockout (KO) mouse model, the role of this critical protein in regulating brain development during embryogenesis and beyond remains a major scientific interest. Rb is a tumor suppressor gene known as the master regulator of the G1/S checkpoint and control of cell cycle progression in stem and progenitor cells, but also their differentiated progeny. Here, we review the recent literature about the various Rb conditional Knockout (cKO) and inducible Knockout (iKO) models studied thus far, highlighting how findings should always be interpreted in light of the model and context under inquiry especially when studying the role of Rb in neuronal survival. There is indeed evidence of age-specific, cell type-specific and region-specific effects following Rb KO in the embryonic and the adult mouse brain. In terms of modeling neurodegenerative processes in human diseases, we discuss cell cycle re-entry (CCE) as a candidate mechanism underlying the increased vulnerability of Rb-deficient neurons to cell death. Notably, mouse models may limit the extent to which CCE due to Rb inactivation can mimic the pathological course of these disorders, such as Alzheimer's disease. These remarks ought to be considered in future research when studying the consequences of Rb inactivation on neuronal generation and survival in rodents and their corresponding clinical significance in humans.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"4 ","pages":"Article 100074"},"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/df/82/main.PMC9869410.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10628283","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":"Unraveling the links between neurodegeneration and Epstein-Barr virus-mediated cell cycle dysregulation","authors":"Deeksha Tiwari ,&nbsp;Nitish Mittal ,&nbsp;Hem Chandra Jha","doi":"10.1016/j.crneur.2022.100046","DOIUrl":"10.1016/j.crneur.2022.100046","url":null,"abstract":"<div><p>The Epstein-Barr virus is a well-known cell cycle modulator. To establish successful infection in the host, EBV alters the cell cycle at multiple steps via antigens such as EBNAs, LMPs, and certain other EBV-encoded transcripts. Interestingly, several recent studies have indicated the possibility of EBV's neurotrophic potential. However, the effects and outcomes of EBV infection in the CNS are under-explored. Additionally, more and more epidemiological evidence implicates the cell-cycle dysregulation in neurodegeneration. Numerous hypotheses which describe the triggers that force post-mitotic neurons to re-enter the cell cycle are prevalent. Apart from the known genetic and epigenetic factors responsible, several reports have shown the association of microbial infections with neurodegenerative pathology. Although, studies implicating the herpesvirus family members in neurodegeneration exist, the involvement of Epstein-Barr virus (EBV), in particular, is under-evaluated. Interestingly, a few clinical studies have reported patients of AD or PD to be seropositive for EBV. Based on the findings mentioned above, in this review, we propose that EBV infection in neurons could drive it towards neurodegeneration through dysregulation of cell-cycle events and induction of apoptosis.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"3 ","pages":"Article 100046"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f1/9a/main.PMC9846474.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9184389","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":"Sex-dependent sensitivity to positive allosteric modulation of GABA action in an APP knock-in mouse model of Alzheimer's disease: Potential epigenetic regulation","authors":"James Auta ,&nbsp;Andrea Locci ,&nbsp;Alessandro Guidotti ,&nbsp;John M. Davis ,&nbsp;Hongxin Dong","doi":"10.1016/j.crneur.2021.100025","DOIUrl":"10.1016/j.crneur.2021.100025","url":null,"abstract":"<div><p>Conflicting evidence suggest that perturbations of GABAergic neurotransmission play crucial roles in disrupting cortical neuronal network oscillations, memory, and cognitive deficits in Alzheimer's disease (AD). However, the role and impact of sex differences on GABAergic transmission in AD are not well understood. Using an APP knock-in mouse model of AD, APP^NLGF mice, we studied the effects of acute diazepam administration on memory and anxiety-like behavior to unveil sex-dependent dysregulation of GABAergic neurotransmission. We also examined sex differences in GABA_A receptor subunit mRNA and protein expression and the role of epigenetic regulation in hippocampus of APP^NLGF mice. We found that diazepam elicited dose-dependent suppression of locomotion in wildtype and APP^NLGF mice. However, a low dose, which had no significant effect in both male and female wildtype as well as female APP^NLGF mice, significantly suppressed locomotion in male APP^NLGF mice. Furthermore, this low dose of diazepam was more efficacious at eliciting anxiolytic-like effects in male than female APP^NLGF mice. The same low dose of diazepam disrupted recognition memory exclusively in male APP^NLGF mice. Biochemical analyses revealed that hippocampal α1 and α5 GABA_A receptor subunits mRNA and protein expression were significantly higher in male than female APP^NLGF mice and were regulated by histone H3 tri-methylation (H3K4me3) but not histone H3 acetylation. The higher sensitivity of APP^NLGF males to diazepam-induced behavioral effects may potentially be due to epigenetic-dependent upregulation of hippocampal α1 and α5 GABA_A receptor subunits expression compared to female APP^NLGF mice. These findings suggest that dysregulation of GABAergic neurotransmission plays a significant role in memory and affective behavior, particularly in male APP^NLGF mice.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"3 ","pages":"Article 100025"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/18/0f/main.PMC9743067.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10361735","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":"Commentary on Unnecessary reliance on multilevel modelling to analyse nested data in neuroscience: When a traditional summary-statistics approach suffices","authors":"Paul Alexander Bloom PhD ,&nbsp;Monica Kim Ngan Thieu PhD ,&nbsp;Niall Bolger PhD","doi":"10.1016/j.crneur.2022.100041","DOIUrl":"10.1016/j.crneur.2022.100041","url":null,"abstract":"","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"3 ","pages":"Article 100041"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9846465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10581802","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 complex relationship between gut microbiota dysregulation and mood disorders: A narrative review","authors":"Agnese Minuti,&nbsp;Francesca Brufani,&nbsp;Giulia Menculini,&nbsp;Patrizia Moretti,&nbsp;Alfonso Tortorella","doi":"10.1016/j.crneur.2022.100044","DOIUrl":"10.1016/j.crneur.2022.100044","url":null,"abstract":"<div><p>Gut microbiota regulates neurotransmission, neurogenesis, neuroinflammation, and neuroendocrine signaling. The aim of the present review is to analyze the literature concerning gut microbiota dysregulation and mood symptoms, with the specific hypothesis that such alterations play a role in the onset of mood disorders. Here, in fact, we review recent research focusing on how gut microbiota dysregulation influences the onset of mood disorders and on possible pathophysiological mechanisms involved in this interaction. We pay specific attention to the relationship between gut microbiota dysregulation and inflammatory state, Th17 differentiation, neuroactive factors, and TRP metabolism. The association between gut microbiota dysregulation and mood disorders is critically analyzed under a clinical point of view, also focusing on the emergence of mood symptoms in the context of medical conditions.</p><p>These latter correlations may enable an interdisciplinary perspective in the clinical approach to such symptoms, as well as new treatment strategies, such as nutritional interventions, psychobiotics, antibiotics, as well as fecal microbiota transplantation.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"3 ","pages":"Article 100044"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ea/64/main.PMC9846469.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10586916","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":"An active inference model of conscious access: How cognitive action selection reconciles the results of report and no-report paradigms","authors":"Christopher J. Whyte ,&nbsp;Jakob Hohwy ,&nbsp;Ryan Smith","doi":"10.1016/j.crneur.2022.100036","DOIUrl":"10.1016/j.crneur.2022.100036","url":null,"abstract":"<div><p>Cognitive theories of consciousness, such as global workspace theory and higher-order theories, posit that frontoparietal circuits play a crucial role in conscious access. However, recent studies using no-report paradigms have posed a challenge to cognitive theories by demonstrating conscious accessibility in the apparent absence of prefrontal cortex (PFC) activation. To address this challenge, this paper presents a computational model of conscious access, based upon active inference, that treats working memory gating as a cognitive action. We simulate a visual masking task and show that late P3b-like event-related potentials (ERPs), and increased PFC activity, are induced by the working memory demands of self-report generation. When reporting demands are removed, these late ERPs vanish and PFC activity is reduced. These results therefore reproduce, and potentially explain, results from no-report paradigms. However, even without reporting demands, our model shows that simulated PFC activity on visible stimulus trials still crosses the threshold for reportability – maintaining the link between PFC and conscious access. Therefore, our simulations show that evidence provided by no-report paradigms does not necessarily contradict cognitive theories of consciousness.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"3 ","pages":"Article 100036"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2b/2b/main.PMC9593308.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9152997","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":"Cognitive and neural principles of a memory bias on preferential choices","authors":"Peter M. Kraemer ,&nbsp;Regina A. Weilbächer ,&nbsp;Tehilla Mechera-Ostrovsky ,&nbsp;Sebastian Gluth","doi":"10.1016/j.crneur.2022.100029","DOIUrl":"10.1016/j.crneur.2022.100029","url":null,"abstract":"<div><p>Value-based decisions depend on different forms of memory. However, the respective roles of memory and valuation processes that give rise to these decisions are often vaguely described and have rarely been investigated jointly. In this review article, we address the problem of memory-based decision making from a neuroeconomic perspective. We first describe the neural and cognitive processes involved in decisions requiring memory processes, with a focus on episodic memory. Based on the results of a systematic research program, we then spotlight the phenomenon of the memory bias, a general preference for choice options that can be retrieved from episodic memory more successfully. Our findings indicate that failed memory recall biases neural valuation processes as indicated by altered effective connectivity between the hippocampus and ventromedial prefrontal cortex. This bias can be attributed to meta-cognitive beliefs about the relationship between subjective value and memory as well as to uncertainty aversion. After summarizing the findings, we outline potential future research endeavors to integrate the two research traditions of memory and decision making.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"3 ","pages":"Article 100029"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9846459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10581805","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":"A little goes a long way: Neurobiological effects of low intensity rTMS and implications for mechanisms of rTMS","authors":"Jessica Moretti ,&nbsp;Jennifer Rodger","doi":"10.1016/j.crneur.2022.100033","DOIUrl":"10.1016/j.crneur.2022.100033","url":null,"abstract":"<div><p>Repetitive transcranial magnetic stimulation (rTMS) is a widespread technique in neuroscience and medicine, however its mechanisms are not well known. In this review, we consider intensity as a key therapeutic parameter of rTMS, and review the studies that have examined the biological effects of rTMS using magnetic fields that are orders of magnitude lower that those currently used in the clinic. We discuss how extensive characterisation of “low intensity” rTMS has set the stage for translation of new rTMS parameters from a mechanistic evidence base, with potential for innovative and effective therapeutic applications. Low-intensity rTMS demonstrates neurobiological effects across healthy and disease models, which include depression, injury and regeneration, abnormal circuit organisation, tinnitus etc. Various short and long-term changes to metabolism, neurotransmitter release, functional connectivity, genetic changes, cell survival and behaviour have been investigated and we summarise these key changes and the possible mechanisms behind them. Mechanisms at genetic, molecular, cellular and system levels have been identified with evidence that low-intensity rTMS and potentially rTMS in general acts through several key pathways to induce changes in the brain with modulation of internal calcium signalling identified as a major mechanism. We discuss the role that preclinical models can play to inform current clinical research as well as uncover new pathways for investigation.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"3 ","pages":"Article 100033"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ea/88/main.PMC9846462.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10586917","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}