Neurobiology of Disease最新文献

{"title":"Peripheral blood immune cells from individuals with Parkinson's disease or inflammatory bowel disease share deficits in iron storage and transport that are modulated by non-steroidal anti-inflammatory drugs","authors":"MacKenzie L. Bolen ,&nbsp;Beatriz Nuñes Gomes ,&nbsp;Blake Gill ,&nbsp;Kelly B. Menees ,&nbsp;Hannah Staley ,&nbsp;Janna Jernigan ,&nbsp;Nikolaus R. McFarland ,&nbsp;Ellen M. Zimmermann ,&nbsp;Christopher E. Forsmark ,&nbsp;Malú Gámez Tansey","doi":"10.1016/j.nbd.2025.106794","DOIUrl":"10.1016/j.nbd.2025.106794","url":null,"abstract":"<div><div>Parkinson's Disease (PD) is a multisystem disorder in which dysregulated neuroimmune crosstalk and inflammatory relay via the gut-blood-brain axis have been implicated in PD pathogenesis. Although alterations in circulating inflammatory cytokines and reactive oxygen species (ROS) have been associated with PD, no biomarkers have been identified that predict clinical progression or disease outcome. Gastrointestinal (GI) dysfunction, which involves perturbation of the underlying immune system, is an early and often-overlooked symptom that affects up to 80 % of individuals living with PD. Interestingly, 50–70 % of individuals with inflammatory bowel disease (IBD), a GI condition that has been epidemiologically linked to PD, display chronic illness-induced anemia — which drives toxic accumulation of iron in the gut. Ferroptotic (or iron loaded) cells have small and dysmorphic mitochondria—suggesting that mitochondrial dysfunction is a consequence of iron accumulation. In pro-inflammatory environments, iron accumulates in immune cells, suggesting a possible connection and/or synergy between iron dysregulation and immune cell dysfunction. Peripheral blood mononuclear cells (PBMCs) recapitulate certain PD-associated neuropathological and inflammatory signatures and can act as communicating messengers in the gut-brain axis. Additionally, this communication can be modulated by several environmental factors; specifically, our data further support existing literature demonstrating a role for non-steroidal anti-inflammatory drugs (NSAIDs) in modulating immune transcriptional states in inflamed individuals. A mechanism linking chronic gut inflammation to iron dysregulation and mitochondrial function within peripheral immune cells has yet to be identified in conferring risk for PD. To that end, we isolated PBMCs and simultaneously evaluated their directed transcriptome and bioenergetic status, to investigate if iron dysregulation and mitochondrial sensitization are linked in individuals living with PD or IBD because of chronic underlying remittent immune activation. We have identified shared features of peripheral inflammation and immunometabolism in individuals living with IBD or PD that may contribute to the epidemiological association reported between IBD and risk for PD.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"207 ","pages":"Article 106794"},"PeriodicalIF":5.1,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142978754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peripherally administered TNF inhibitor is not protective against α-synuclein-induced dopaminergic neuronal death in rats","authors":"Josefine R. Christiansen ,&nbsp;Sara A. Ferreira ,&nbsp;David E. Szymkowski ,&nbsp;Johan Jakobsson ,&nbsp;Malú Gámez Tansey ,&nbsp;Marina Romero-Ramos","doi":"10.1016/j.nbd.2025.106803","DOIUrl":"10.1016/j.nbd.2025.106803","url":null,"abstract":"<div><div>The underlying cause of neuronal loss in Parkinson's disease (PD) remains unknown, but evidence implicates neuroinflammation in PD pathobiology. The pro-inflammatory cytokine soluble tumor necrosis factor (TNF) seems to play an important role and thus has been proposed as a therapeutic target for modulation of the neuroinflammatory processes in PD. In this regard, dominant-negative TNF (DN-TNF) agents are promising antagonists that selectively inhibit soluble TNF signaling, while preserving the beneficial effects of transmembrane TNF. Previous studies have tested the protective potential of DN-TNF-based therapy in toxin-based PD models. Here we test for the first time the protective potential of a DN-TNF therapeutic against α-synuclein-driven neurodegeneration in the viral vector-based PD female rat model. To do so, we administered the DN-TNF agent XPro1595 subcutaneously for a period of 12 weeks. In contrast to previous studies using different PD models, neuroprotection was not achieved by systemic XPro1595 treatment. α-Synuclein-induced loss of nigrostriatal neurons, accumulation of pathological inclusions and microgliosis was detected in both XPro1595- and saline-treated animals. XPro1595 treatment increased the percentage of the hypertrophic/ameboid Iba1+ cells in SN and reduced the striatal MHCII+ expression in the α-synuclein-overexpressing animals. However, the treatment did not prevent the MHCII upregulation seen in the SN of the model, nor the increase of CD68+ phagocytic cells. Therefore, despite an apparently immunomodulatory effect, this did not suffice to protect against viral vector-derived α-synuclein-induced neurotoxicity. Further studies are warranted to better elucidate the therapeutic potential of soluble TNF inhibitors in PD.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"206 ","pages":"Article 106803"},"PeriodicalIF":5.1,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The brain interactome of a permissive prion replication substrate","authors":"Hamza Arshad ,&nbsp;Shehab Eid ,&nbsp;Surabhi Mehra ,&nbsp;Declan Williams ,&nbsp;Lech Kaczmarczyk ,&nbsp;Erica Stuart ,&nbsp;Walker S. Jackson ,&nbsp;Gerold Schmitt-Ulms ,&nbsp;Joel C. Watts","doi":"10.1016/j.nbd.2025.106802","DOIUrl":"10.1016/j.nbd.2025.106802","url":null,"abstract":"<div><div>Bank voles are susceptible to prion strains from many different species, yet the molecular mechanisms underlying the ability of bank vole prion protein (BVPrP) to function as a universal prion acceptor remain unclear. Potential differences in molecular environments and protein interaction networks on the cell surface of brain cells may contribute to BVPrP's unusual behavior. To test this hypothesis, we generated knock-in mice that express physiological levels of BVPrP (M109 isoform) and employed mass spectrometry to compare the interactomes of mouse (Mo) PrP and BVPrP following mild in vivo crosslinking of brain tissue. Substantial overlap was observed between the top interactors for BVPrP and MoPrP, with established PrP-interactors such as neural cell adhesion molecules, subunits of Na⁺/K⁺-ATPases, and contactin-1 being equally present in the two interactomes. We conclude that the molecular environments of BVPrP and MoPrP in the brains of mice are very similar. This suggests that the unorthodox properties of BVPrP are unlikely to be mediated by differential interactions with other proteins.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"206 ","pages":"Article 106802"},"PeriodicalIF":5.1,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebral cortical functional hyperconnectivity in a mouse model of spinocerebellar ataxia type 8 (SCA8)","authors":"Angela K. Nietz ,&nbsp;Laurentiu S. Popa ,&nbsp;Russell E. Carter ,&nbsp;Morgan L. Gerhart ,&nbsp;Keerthi Manikonda ,&nbsp;Laura P.W. Ranum ,&nbsp;Timothy J. Ebner","doi":"10.1016/j.nbd.2025.106795","DOIUrl":"10.1016/j.nbd.2025.106795","url":null,"abstract":"<div><div>Spinocerebellar Ataxia Type 8 (SCA8) is an inherited neurodegenerative disease caused by a bidirectionally expressed CTG•CAG expansion mutation in the <em>ATXN8</em> and <em>ATXN8OS</em> genes. While SCA8 patients have motor abnormalities, patients may also exhibit psychiatric symptoms and cognitive dysfunction. It is difficult to elucidate how the disease alters brain function in areas with little or no degeneration producing both motor and cognitive symptoms. Using transparent polymer skulls and CNS-wide GCaMP6f expression, we studied neocortical networks throughout SCA8 progression using wide-field Ca²⁺ imaging in a transgenic mouse model of SCA8. Compared to wild-type controls, neocortical networks in SCA8+ mice were hyperconnected globally, which leads to network configurations with increased global efficiency and centrality. At the regional level, significant network changes occurred in nearly all cortical regions, however mainly involved sensory and association cortices. Changes in functional connectivity in anterior motor regions worsened later in the disease. Near perfect decoding of animal genotype was obtained using a generalized linear model based on canonical correlation strengths between activity in cortical regions. The major contributors to decoding were concentrated in the somatosensory, higher visual and retrosplenial cortices and occasionally extended into the motor regions, demonstrating that the areas with the largest network changes are predictive of disease state.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"206 ","pages":"Article 106795"},"PeriodicalIF":5.1,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reactivation of mTOR signaling slows neurodegeneration in a lysosomal sphingolipid storage disease","authors":"Hongling Zhu ,&nbsp;Y. Terry Lee ,&nbsp;Colleen Byrnes ,&nbsp;Jabili Angina ,&nbsp;Danielle A. Springer ,&nbsp;Galina Tuymetova ,&nbsp;Mari Kono ,&nbsp;Cynthia J. Tifft ,&nbsp;Richard L. Proia","doi":"10.1016/j.nbd.2024.106760","DOIUrl":"10.1016/j.nbd.2024.106760","url":null,"abstract":"<div><div>Sandhoff disease, a lysosomal storage disorder, is caused by pathogenic variants in the <em>HEXB</em> gene, resulting in the loss of β-hexosaminidase activity and accumulation of sphingolipids including GM2 ganglioside. This accumulation occurs primarily in neurons, and leads to progressive neurodegeneration through a largely unknown process. Lysosomal storage diseases often exhibit dysfunctional mTOR signaling, a pathway crucial for proper neuronal development and function. In this study, Sandhoff disease model mice exhibited reduced mTOR signaling in the brain. To test if restoring mTOR signaling could improve the disease phenotype, we genetically reduced expression of the mTOR inhibitor Tsc2 in these mice. Sandhoff disease mice with reactivated mTOR signaling displayed increased survival rates and motor function, especially in females, increased dendritic-spine density, and reduced neurodegeneration. Tsc2 reduction also partially rescued aberrant synaptic function–related gene expression. These findings imply that enhancing mTOR signaling could be a potential therapeutic strategy for lysosomal-based neurodegenerative diseases.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"204 ","pages":"Article 106760"},"PeriodicalIF":5.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Common lipidomic signatures across distinct acute brain injuries in patient outcome prediction","authors":"Santtu Hellström ,&nbsp;Antti Sajanti ,&nbsp;Abhinav Srinath ,&nbsp;Carolyn Bennett ,&nbsp;Romuald Girard ,&nbsp;Aditya Jhaveri ,&nbsp;Ying Cao ,&nbsp;Johannes Falter ,&nbsp;Janek Frantzén ,&nbsp;Fredrika Koskimäki ,&nbsp;Seán B. Lyne ,&nbsp;Tomi Rantamäki ,&nbsp;Riikka Takala ,&nbsp;Jussi P. Posti ,&nbsp;Susanna Roine ,&nbsp;Sulo Kolehmainen ,&nbsp;Kenneth Nazir ,&nbsp;Miro Jänkälä ,&nbsp;Jukka Puolitaival ,&nbsp;Melissa Rahi ,&nbsp;Janne Koskimäki","doi":"10.1016/j.nbd.2024.106762","DOIUrl":"10.1016/j.nbd.2024.106762","url":null,"abstract":"<div><div>Lipidomic alterations have been associated with various neurological diseases. Examining temporal changes in serum lipidomic profiles, irrespective of injury type, reveals promising prognostic indicators. In this longitudinal prospective observational study, serum samples were collected early (46 ± 24 h) and late (142 ± 52 h) post-injury from 70 patients with ischemic stroke, aneurysmal subarachnoid hemorrhage, and traumatic brain injury that had outcomes dichotomized as favorable (modified Rankin Scores (mRS) 0–3) and unfavorable (mRS 4–6) three months post-injury. Lipidomic profiling of 1153 lipids, analyzed using statistical and machine learning methods, identified 153 lipids with late-stage significant outcome differences. Supervised machine learning pinpointed 12 key lipids, forming a combinatory prognostic equation with high discriminatory power (AUC 94.7 %, sensitivity 89 %, specificity 92 %; <em>p</em> &lt; 0.0001). Enriched functions of the identified lipids were related to sphingolipid signaling, glycerophospholipid metabolism, and necroptosis (<em>p</em> &lt; 0.05, FDR-corrected). The study underscores the dynamic nature of lipidomic profiles in acute brain injuries, emphasizing late-stage distinctions and proposing lipids as significant prognostic markers, transcending injury types. These findings advocate further exploration of lipidomic changes for a comprehensive understanding of pathobiological roles and enhanced prediction for recovery trajectories.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"204 ","pages":"Article 106762"},"PeriodicalIF":5.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Instationary metabolic flux analysis reveals that NPC1 inhibition increases glycolysis and decreases mitochondrial metabolism in brain microvascular endothelial cells","authors":"Bilal Moiz ,&nbsp;Matthew Walls ,&nbsp;Viviana Alpizar Vargas ,&nbsp;Anirudh Addepalli ,&nbsp;Callie Weber ,&nbsp;Andrew Li ,&nbsp;Ganesh Sriram ,&nbsp;Alisa Morss Clyne","doi":"10.1016/j.nbd.2024.106769","DOIUrl":"10.1016/j.nbd.2024.106769","url":null,"abstract":"<div><div>Niemann Pick Disease Type C (NP-C), a rare neurogenetic disease with no known cure, is caused by mutations in the cholesterol trafficking protein NPC1. Brain microvascular endothelial cells (BMEC) are thought to play a critical role in the pathogenesis of several neurodegenerative diseases; however, little is known about how these cells are altered in NP-C. In this study, we investigated how NPC1 inhibition perturbs BMEC metabolism in human induced pluripotent stem cell-derived BMEC (hiBMEC). We incorporated extracellular metabolite and isotope labeling data into an instationary metabolic flux analysis (INST-MFA) model to estimate intracellular metabolic fluxes. We found that NPC1 inhibition significantly increased glycolysis and pentose phosphate pathway flux while decreasing mitochondrial metabolism. These changes may have been driven by gene expression changes due to increased cholesterol biosynthesis, in addition to mitochondrial cholesterol accumulation. We corroborated these findings in primary BMEC, an alternative in vitro human brain endothelial model. Finally, we found that co-treatment with hydroxypropyl-β cyclodextrin (HPβCD) partially restored metabolic phenotype in U18666A-treated BMECs, suggesting that this drug may have therapeutic effects on the brain endothelium in NP-C. Together, our data highlight the importance of NPC1 in BMEC metabolism and implicate brain endothelial dysfunction in NP-C pathogenesis.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"204 ","pages":"Article 106769"},"PeriodicalIF":5.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Excitatory synaptic structural abnormalities produced by templated aggregation of α-syn in the basolateral amygdala” [Neurobiology of Disease 199 (2024) 106595]","authors":"Nolwazi Z. Gcwensa ,&nbsp;Dreson L. Russell ,&nbsp;Khaliah Y. Long ,&nbsp;Charlotte F. Brzozowski ,&nbsp;Xinran Liu ,&nbsp;Karen L. Gamble ,&nbsp;Rita M. Cowell ,&nbsp;Laura A. Volpicelli-Daley","doi":"10.1016/j.nbd.2024.106757","DOIUrl":"10.1016/j.nbd.2024.106757","url":null,"abstract":"","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"204 ","pages":"Article 106757"},"PeriodicalIF":5.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repeated low-intensity noise exposure exacerbates age-related hearing loss via RAGE signaling pathway","authors":"Jianbin Sun ,&nbsp;Na Sai ,&nbsp;Tong Zhang ,&nbsp;Chaoying Tang ,&nbsp;Shuhang Fan ,&nbsp;Qin Wang ,&nbsp;Da Liu ,&nbsp;Xianhai Zeng ,&nbsp;Juanjuan Li ,&nbsp;Weiwei Guo ,&nbsp;Shiming Yang ,&nbsp;Weiju Han","doi":"10.1016/j.nbd.2024.106768","DOIUrl":"10.1016/j.nbd.2024.106768","url":null,"abstract":"<div><div>Repeated low-intensity noise exposure is prevalent in industrialized societies. It has long been considered risk-free until recent evidence suggests that the temporary threshold shift (TTS) induced by such exposure might be a high-risk factor for hearing loss. This study was conducted to further investigate the manner in which repeated low-intensity noise exposure contributed to hearing damage. Two-month-old C57BL/6 J mice were exposed to white noise at 96 dB SPL for 8 h per day over 7 days to induce TTS. Auditory brainstem response (ABR) was monitored to assess changes in hearing thresholds, tracking the effects of noise exposure until the mice reached 12 months of age. Our results indicated that noise-exposed mice exhibited accelerated age-related hearing loss spanning from high to low frequencies. Proteomics analysis revealed an upregulation in the receptor for the advanced glycation end-products (RAGE) signaling pathway, which was associated with an activated inflammatory response, vascular injury, and mitochondrial and synaptic dysfunction. Further analysis confirmed increased levels of inflammatory cytokines in the cochlear lymph fluid and significant macrophages infiltration in the cochlear lateral wall, accompanied by hyperpermeability of the blood-labyrinth barrier. Additionally, degenerated mitochondria in the outer hair cells and decreased synaptic ribbons in the inner hair cells were also observed. These pathological changes indicated that noise exposure damages the cochlear cellular components, increasing the cochlear susceptibility to age-related stress. Our findings suggest that TTS caused by repeated low-intensity noise exposure correlates with a severe sensorineural hearing loss during aging; targeting the RAGE signaling pathway may be a promising strategy to mitigate damage from low-intensity noise and slow down the progression of age-related hearing loss.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"204 ","pages":"Article 106768"},"PeriodicalIF":5.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lateral periaqueductal gray participate in the regulation of irritable bowel syndrome induced by chronic restraint stress","authors":"Jiaotao Xing ,&nbsp;Ying Li ,&nbsp;Jiali Hu ,&nbsp;Liyao Gu ,&nbsp;Guanghua Sun ,&nbsp;Xiangle Li","doi":"10.1016/j.nbd.2024.106758","DOIUrl":"10.1016/j.nbd.2024.106758","url":null,"abstract":"<div><div>Irritable bowel syndrome (IBS) is a functional bowel disorder defined by recurrent abdominal pain, coupled with irregular bowel habits and alterations in the frequency as well as the consistency of stool. At present, IBS is considered as a disease of gut-brain interaction, and an increasing number of studies are focusing on the brain-gut axis. However, the brain regions associated with IBS have not been fully studied yet. In this study, we utilized the chronic restraint stress (CRS) model to evoke IBS-like symptoms in mice, which were accompanied by anxiety-like behaviors and hyperalgesia. Through cFOS staining, we observed the activation of the lateral periaqueductal gray (LPAG) in the mice after CRS. By inhibiting the activity of the LPAG through tetanus toxin or chemogenetics, we found that IBS-like symptoms could be relieved, whereas chemogenetic activation of the LPAG induced IBS-like symptoms. Finally, we utilized the classic analgesic drug sufentanil and found that it could alleviate CRS-induced IBS-like symptoms.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"204 ","pages":"Article 106758"},"PeriodicalIF":5.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}