{"title":"Distinct Role of Parvalbumin Expressing Neurons in the Reticular Thalamic Nucleus in Nociception.","authors":"Sanggeon Park, Jeiwon Cho, Yeowool Huh","doi":"10.5607/en23018","DOIUrl":"10.5607/en23018","url":null,"abstract":"<p><p>Loss of inhibition is suggested to cause pathological pain symptoms. Indeed, some human case reports suggest that lesions including the thalamic reticular nucleus (TRN) which provides major inhibitory inputs to other thalamic nuclei, may induce thalamic pain, a type of neuropathic pain. In support, recent studies demonstrated that activation of GABAergic neurons in the TRN reduces nociceptive responses in mice, reiterating the importance of the TRN in gating nociception. However, whether biochemically distinct neuronal types in the TRN differentially contribute to gating nociception has not been investigated. We, therefore, investigated whether the activity of parvalbumin (PV) and somatostatin (SOM) expressing neurons in the somatosensory TRN differentially modulate nociceptive behaviors using optogenetics and immunostaining techniques. We found that activation of PV neurons in the somatosensory TRN significantly reduced nociceptive behaviors, while activation of SOM neurons in the TRN had no such effect. Also, selective activation of PV neurons, but not SOM neurons, in the TRN activated relatively more PV neurons in the primary somatosensory cortex, which delivers inhibitory effect in the cortex, when measured with cFos and PV double staining. Results of our study suggest that PV neurons in the somatosensory TRN have a stronger influence in regulating nociception and that their activations may provide further inhibition in the somatosensory cortex by activating cortical PV neurons.</p>","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"32 6","pages":"387-394"},"PeriodicalIF":2.4,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10789177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139402477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wonseok Son, Hui Su Jeong, Da Eun Nam, Ah Jin Lee, Soo Hyun Nam, Ji Eun Lee, Byung-Ok Choi, Ki Wha Chung
{"title":"Peripheral Neuropathy and Decreased Locomotion of a <i>RAB40B</i> Mutation in Human and Model Animals.","authors":"Wonseok Son, Hui Su Jeong, Da Eun Nam, Ah Jin Lee, Soo Hyun Nam, Ji Eun Lee, Byung-Ok Choi, Ki Wha Chung","doi":"10.5607/en23027","DOIUrl":"10.5607/en23027","url":null,"abstract":"<p><p>Rab40 proteins are an atypical subgroup of Rab GTPases containing a unique suppressor of the cytokine signaling (SOCS) domain that is recruited to assemble the CRL5 E3 ligase complex for proteolytic regulation in various biological processes. A nonsense mutation deleting the C-terminal SOCS box in the <i>RAB40B</i> gene was identified in a family with axonal peripheral neuropathy (Charcot-Marie-Tooth disease type 2), and pathogenicity of the mutation was assessed in model organisms of zebrafish and <i>Drosophila</i>. Compared to control fish, zebrafish larvae transformed by the human mutant <i>hRAB40B</i><i>-Y83X</i> showed a defective swimming pattern of stalling with restricted localization and slower motility. We were consistently able to observe reduced labeling of synaptic markers along neuromuscular junctions of the transformed larvae. In addition to the neurodevelopmental phenotypes, compared to normal <i>hRAB40B</i> expression, we further examined ectopic expression of <i>hRAB40B</i><i>-Y83X</i> in <i>Drosophila</i> to show a progressive decline of locomotion ability. Decreased ability of locomotion by ubiquitous expression of the human mutation was reproduced not with GAL4 drivers for neuron-specific expression but only when a pan-glial GAL4 driver was applied. Using the ectopic expression model of <i>Drosophila</i>, we identified a genetic interaction in which <i>Cul5</i> down regulation exacerbated the defective motor performance, showing a consistent loss of SOCS box of the pathogenic RAB40B. Taken together, we could assess the possible gain-of-function of the human <i>RAB40B</i> mutation by comparing behavioral phenotypes in animal models; our results suggest that the mutant phenotypes may be associated with CRL5-mediated proteolytic regulation.</p>","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"32 6","pages":"410-422"},"PeriodicalIF":2.4,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10789172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139402479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mapping Astrocytic and Neuronal μ-opioid Receptor Expression in Various Brain Regions Using MOR-mCherry Reporter Mouse.","authors":"Woojin Won, Daeun Kim, Eunjin Shin, C Justin Lee","doi":"10.5607/en23039","DOIUrl":"10.5607/en23039","url":null,"abstract":"<p><p>The μ-opioid receptor (MOR) is a class of opioid receptors characterized by a high affinity for β-endorphin and morphine. MOR is a G protein-coupled receptor (GPCR) that plays a role in reward and analgesic effects. While expression of MOR has been well established in neurons and microglia, astrocytic MOR expression has been less clear. Recently, we have reported that MOR is expressed in hippocampal astrocytes, and its activation has a critical role in the establishment of conditioned place preference. Despite this critical role, the expression and function of astrocytic MOR from other brain regions are still unknown. Here, we report that MOR is significantly expressed in astrocytes and GABAergic neurons from various brain regions including the hippocampus, nucleus accumbens, periaqueductal gray, amygdala, and arcuate nucleus. Using the MOR-mCherry reporter mice and Imaris analysis, we demonstrate that astrocytic MOR expression exceeded 60% in all tested regions. Also, we observed similar MOR expression of GABAergic neurons as shown in the previous distribution studies and it is noteworthy that MOR expression is particularly in parvalbumin (PV)-positive neurons. Furthermore, consistent with the normal MOR function observed in the MOR-mCherry mouse, our study also demonstrates intact MOR functionality in astrocytes through iGluSnFr-mediated glutamate imaging. Finally, we show the sex-difference in the expression pattern of MOR in PV-positive neurons, but not in the GABAergic neurons and astrocytes. Taken together, our findings highlight a substantial astrocytic MOR presence across various brain regions.</p>","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"32 6","pages":"395-409"},"PeriodicalIF":2.4,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10789176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139402478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Geoffrey Canet, Emma Rocaboy, Francis Laliberté, Emmanuelle Boscher, Isabelle Guisle, Sofia Diego-Diaz, Parissa Fereydouni-Forouzandeh, Robert A Whittington, Sébastien S Hébert, Vincent Pernet, Emmanuel Planel
{"title":"Temperature-induced Artifacts in Tau Phosphorylation: Implications for Reliable Alzheimer's Disease Research.","authors":"Geoffrey Canet, Emma Rocaboy, Francis Laliberté, Emmanuelle Boscher, Isabelle Guisle, Sofia Diego-Diaz, Parissa Fereydouni-Forouzandeh, Robert A Whittington, Sébastien S Hébert, Vincent Pernet, Emmanuel Planel","doi":"10.5607/en23025","DOIUrl":"10.5607/en23025","url":null,"abstract":"<p><p>In preclinical research on Alzheimer's disease and related tauopathies, tau phosphorylation analysis is routinely employed in both cellular and animal models. However, recognizing the sensitivity of tau phosphorylation to various extrinsic factors, notably temperature, is vital for experimental accuracy. Hypothermia can trigger tau hyperphosphorylation, while hyperthermia leads to its dephosphorylation. Nevertheless, the rapidity of tau phosphorylation in response to unintentional temperature variations remains unknown. In cell cultures, the most significant temperature change occurs when the cells are removed from the incubator before harvesting, and in animal models, during anesthesia prior to euthanasia. In this study, we investigate the kinetics of tau phosphorylation in N2a and SH-SY5Y neuronal cell lines, as well as in mice exposed to anesthesia. We observed changes in tau phosphorylation within the few seconds upon transferring cell cultures from their 37°C incubator to room temperature conditions. However, cells placed directly on ice post-incubation exhibited negligible phosphorylation changes. In vivo, isoflurane anesthesia rapidly resulted in tau hyperphosphorylation within the few seconds needed to lose the pedal withdrawal reflex in mice. These findings emphasize the critical importance of preventing temperature variation in researches focused on tau. To ensure accurate results, we recommend avoiding anesthesia before euthanasia and promptly placing cells on ice after removal from the incubator. By controlling temperature fluctuations, the reliability and validity of tau phosphorylation studies can be significantly enhanced.</p>","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"32 6","pages":"423-440"},"PeriodicalIF":2.4,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10789175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139402480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Arcuate Nucleus of the Hypothalamus: Anatomy, Physiology, and Diseases.","authors":"Juhyun Song, Seok-Yong Choi","doi":"10.5607/en23040","DOIUrl":"10.5607/en23040","url":null,"abstract":"<p><p>The hypothalamus is part of the diencephalon and has several nuclei, one of which is the arcuate nucleus. The arcuate nucleus of hypothalamus (ARH) consists of neuroendocrine neurons and centrally-projecting neurons. The ARH is the center where the homeostasis of nutrition/metabolism and reproduction are maintained. As such, dysfunction of the ARH can lead to disorders of nutrition/metabolism and reproduction. Here, we review various types of neurons in the ARH and several genetic disorders caused by mutations in the ARH.</p>","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"32 6","pages":"371-386"},"PeriodicalIF":2.4,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10789173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139402475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hyejin Kwon, Eun-Hwa Lee, Juli Choi, Jin-Young Park, Yoon-Keun Kim, Pyung-Lim Han
{"title":"Extracellular Vesicles Released by <i>Lactobacillus paracasei</i> Mitigate Stress-induced Transcriptional Changes and Depression-like Behavior in Mice.","authors":"Hyejin Kwon, Eun-Hwa Lee, Juli Choi, Jin-Young Park, Yoon-Keun Kim, Pyung-Lim Han","doi":"10.5607/en23024","DOIUrl":"10.5607/en23024","url":null,"abstract":"<p><p>Various probiotic strains have been reported to affect emotional behavior. However, the underlying mechanisms by which specific probiotic strains change brain function are not clearly understood. Here, we report that extracellular vesicles derived from <i>Lactobacillus paracasei</i> (<i>Lpc</i>-EV) have an ability to produce genome-wide changes against glucocorticoid (GC)-induced transcriptional responses in HT22 hippocampal neuronal cells. Genome-wide analysis using microarray assay followed by Rank-Rank Hypergeometric Overlap (RRHO) method leads to identify the top 20%-ranked 1,754 genes up- or down-regulated following GC treatment and their altered expressions are reversed by <i>Lpc</i>-EV in HT22 cells. Serial <i>k</i>-means clustering combined with Gene Ontology enrichment analyses indicate that the identified genes can be grouped into multiple functional clusters that contain functional modules of \"responses to stress or steroid hormones\", \"histone modification\", and \"regulating MAPK signaling pathways\". While all the selected genes respond to GC and <i>Lpc</i>-EV at certain levels, the present study focuses on the clusters that contain <i>Mkp-1</i>, <i>Fkbp5</i>, and <i>Mecp2</i>, the genes characterized to respond to GC and <i>Lpc</i>-EV in opposite directions in HT22 cells. A translational study indicates that the expression levels of <i>Mkp-1</i>, <i>Fkbp5</i>, and <i>Mecp2</i> are changed in the hippocampus of mice exposed to chronic stress in the same directions as those following GC treatment in HT22 cells, whereas <i>Lpc</i>-EV treatment restored stress-induced changes of those factors, and alleviated stress-induced depressive-like behavior. These results suggest that <i>Lpc</i>-EV cargo contains bioactive components that directly induce genome-wide transcriptional responses against GC-induced transcriptional and behavioral changes.</p>","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"32 5","pages":"328-342"},"PeriodicalIF":2.4,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10628865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71479887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiyun Lee, Eum-Ji Kim, Gun-Seok Park, Jeongseop Kim, Tae-Eun Kim, Yoo Jin Lee, Juyi Park, Jihee Kang, Ja Wook Koo, Tae-Yong Choi
{"title":"<i>Lactobacillus reuteri</i> ATG-F4 Alleviates Chronic Stress-induced Anhedonia by Modulating the Prefrontal Serotonergic System.","authors":"Jiyun Lee, Eum-Ji Kim, Gun-Seok Park, Jeongseop Kim, Tae-Eun Kim, Yoo Jin Lee, Juyi Park, Jihee Kang, Ja Wook Koo, Tae-Yong Choi","doi":"10.5607/en23028","DOIUrl":"10.5607/en23028","url":null,"abstract":"<p><p>Mental health is influenced by the gut-brain axis; for example, gut dysbiosis has been observed in patients with major depressive disorder (MDD). Gut microbial changes by fecal microbiota transplantation or probiotics treatment reportedly modulates depressive symptoms. However, it remains unclear how gut dysbiosis contributes to mental dysfunction, and how correction of the gut microbiota alleviates neuropsychiatric disorders. Our previous study showed that chronic consumption of <i>Lactobacillus reuteri</i> ATG-F4 (F4) induced neurometabolic alterations in healthy mice. Here, we investigated whether F4 exerted therapeutic effects on depressive-like behavior by influencing the central nervous system. Using chronic unpredictable stress (CUS) to induce anhedonia, a key symptom of MDD, we found that chronic F4 consumption alleviated CUS-induced anhedonic behaviors, accompanied by biochemical changes in the gut, serum, and brain. Serum and brain metabolite concentrations involved in tryptophan metabolism were regulated by CUS and F4. F4 consumption reduced the elevated levels of serotonin (5-HT) in the brain observed in the CUS group. Additionally, the increased expression of <i>Htr1a</i>, a subtype of the 5-HT receptor, in the medial prefrontal cortex (mPFC) of stressed mice was restored to levels observed in stress-naïve mice following F4 supplementation. We further demonstrated the role of <i>Htr1a</i> using AAV-shRNA to downregulate <i>Htr1a</i> in the mPFC of CUS mice, effectively reversing CUS-induced anhedonic behavior. Together, our findings suggest F4 as a potential therapeutic approach for relieving some depressive symptoms and highlight the involvement of the tryptophan metabolism in mitigating CUS-induced depressive-like behaviors through the action of this bacterium.</p>","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"32 5","pages":"313-327"},"PeriodicalIF":2.4,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10628864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71479885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eric Eunshik Kim, Kwanghoon Lee, Ji-Hoon Phi, Min-Sung Kim, Hyoung Jin Kang, Hongseok Yun, Sung-Hye Park
{"title":"Methylation-based Subclassifications of Embryonal Tumor with Multilayered Rosettes in Not Just Pediatric Brains.","authors":"Eric Eunshik Kim, Kwanghoon Lee, Ji-Hoon Phi, Min-Sung Kim, Hyoung Jin Kang, Hongseok Yun, Sung-Hye Park","doi":"10.5607/en23021","DOIUrl":"10.5607/en23021","url":null,"abstract":"The aim of this study is to investigate the genetic profiles and methylation-based classifications of Embryonal tumor with multilayered rosettes (ETMR), with a specific focus on differentiating between C19MC amplified and C19MC-not amplified groups, including cases with DICER1 mutations. To achieve this, next-generation sequencing using a targeted gene panel for brain tumors and methylation class studies using the Epic850K microarray were performed to identify tumor subclasses and their clinicopathological characteristics. The study cohort consisted of four patients, including 3 children (a 4-months/F, a 9-months/M, and a 2 y/F), and one adult (a 30 y/Male). All three tumors in the pediatric patients originated in the posterior fossa and exhibited TTYH1:C19MC fusion and C19MC amplification. The fourth case in the adult patient involved the cerebellopontine angle with biallelic DICER1 mutation. Histopathological examination revealed typical embryonal features characterized by multilayered rosettes and abundant neuropils in all cases, while the DICER1-mutant ETMR also displayed cartilage islands in addition to the classic ETMR pathology. All four tumors showed positive staining for LIN28A. The t-SNE clustering analysis demonstrated that the first three cases clustered with known subtypes of ETMR, specifically C19MC amplified, while the fourth case clustered separately to non-C19MC amplified subclass. During the follow-up period of 6~12 months, leptomeningeal dissemination of the tumor occurred in all patients. Considering the older age of onset in DICER1-mutant ETMR, genetic counseling should be recommended due to the association of DICER1 mutations with germline and second-hit somatic mutations in cancer.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"32 5","pages":"354-361"},"PeriodicalIF":2.4,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10628863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71479889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hyunjung Lee, Joon Hyung Jung, Seungwon Chung, Gawon Ju, Siekyeong Kim, Jung-Woo Son, Chul-Jin Shin, Sang Ick Lee, Jeonghwan Lee
{"title":"Graph Theoretical Analysis of Brain Structural Connectivity in Patients with Alcohol Dependence.","authors":"Hyunjung Lee, Joon Hyung Jung, Seungwon Chung, Gawon Ju, Siekyeong Kim, Jung-Woo Son, Chul-Jin Shin, Sang Ick Lee, Jeonghwan Lee","doi":"10.5607/en23026","DOIUrl":"10.5607/en23026","url":null,"abstract":"<p><p>This study aimed to compare brain structural connectivity using graph theory between patients with alcohol dependence and social drinkers. The participants were divided into two groups; the alcohol group (N=23) consisting of patients who had been hospitalized and had abstained from alcohol for at least three months and the control group (N=22) recruited through advertisements and were social drinkers. All participants were evaluated using 3T magnetic resonance imaging. A total of 1000 repeated whole-brain tractographies with random parameters were performed using DSI Studio. Four hundred functionally defined cortical regions of interest (ROIs) were parcellated using FreeSurfer based on the Schaefer Atlas. The ROIs were overlaid on the tractography results to generate 1000 structural connectivity matrices per person, and 1000 matrices were averaged into a single matrix per subject. Graph analysis was performed through igraph R package. Graph measures were compared between the two groups using analysis of covariance, considering the effects of age and smoking pack years. The alcohol group showed lower local efficiency than the control group in the whole-brain (F=5.824, p=0.020), somato-motor (F=5.963, p=0.019), and default mode networks (F=4.422, p=0.042). The alcohol group showed a lower global efficiency (F=5.736, p=0.021) in the control network. The transitivity of the alcohol group in the dorsal attention network was higher than that of the control (F=4.257, p=0.046). Our results imply that structural stability of the whole-brain network is affected in patients with alcohol dependence, which can lead to ineffective information processing in cases of local node failure.</p>","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"32 5","pages":"362-369"},"PeriodicalIF":2.4,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10628861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71479888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tien Thuy Phan, Nishani Jayanika Jayathilake, Kyu Pil Lee, Joo Min Park
{"title":"BDNF/TrkB Signaling Inhibition Suppresses Astrogliosis and Alleviates Mechanical Allodynia in a Partial Crush Injury Model.","authors":"Tien Thuy Phan, Nishani Jayanika Jayathilake, Kyu Pil Lee, Joo Min Park","doi":"10.5607/en23031","DOIUrl":"10.5607/en23031","url":null,"abstract":"<p><p>Neuropathic pain presents a formidable clinical challenge due to its persistent nature and limited responsiveness to conventional analgesic treatments. While significant progress has been made in understanding the role of spinal astrocytes in neuropathic pain, their contribution and functional changes following a partial crush injury (PCI) remain unexplored. In this study, we investigated structural and functional changes in spinal astrocytes during chronic neuropathic pain, employing a partial crush injury model. This model allowes us to replicate the transition from initial nociceptive responses to persistent pain, highlighting the relevance of astrocytes in pain maintenance and sensitization. Through the examination of mechanical allodynia, a painful sensation in response to innocuous stimuli, and the correlation with increased levels of brain-derived neurotrophic factor (BDNF) along with reactive astrocytes, we identified a potential mechanistic link between astrocytic activity and BDNF signaling. Ultimately, our research provides evidence that inhibiting astrocyte activation through a BDNF/TrkB inhibitor alleviates mechanical allodynia, underscoring the therapeutic potential of targeting glial BDNF-related pathways for pain management. These findings offer critical insights into the cellular and molecular dynamics of neuropathic pain, paving the way for innovative and targeted treatment strategies for this challenging condition.</p>","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"32 5","pages":"343-353"},"PeriodicalIF":2.4,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10628862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71479886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}