Neuropharmacology最新文献

{"title":"Rapamycin exerts neuroprotective effects by inhibiting FKBP12 instead of mTORC1 in the mouse model of Parkinson's disease","authors":"Zeyan Zhang ,&nbsp;Ziyue Shen ,&nbsp;Shiming Xie ,&nbsp;Junyu Li ,&nbsp;Zeyu Zhang ,&nbsp;Sheng Zhang ,&nbsp;Bo Peng ,&nbsp;Qianchu Huang ,&nbsp;Mingtao Li ,&nbsp;Shanshan Ma ,&nbsp;Qiaoying Huang","doi":"10.1016/j.neuropharm.2025.110504","DOIUrl":"10.1016/j.neuropharm.2025.110504","url":null,"abstract":"<div><div>Parkinson's disease (PD), characterized by the selective loss of nigral dopaminergic neurons, is a common neurodegenerative disorder for which effective disease-modifying therapies remain unavailable. Rapamycin, a clinical immunosuppressant used for decades, has demonstrated neuroprotective effects in various animal models of neurological diseases, including PD. These effects are believed to be mediated through the inhibition of mammalian target of rapamycin (mTOR) complex 1 (mTORC1) signaling, with rapamycin binding to FKBP12. However, recent studies have suggested that mTOR activation can be neuroprotective in degenerating dopaminergic neurons, presenting a paradox to the neuroprotective mechanism of rapamycin via mTORC1 inhibition. In this study, we showed that mTORC1 signaling was inactivated in nigral dopaminergic neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. Notably, the optimal neuroprotective dose of rapamycin did not inhibit mTORC1 signaling nor restore autophagy defects in nigral dopaminergic neurons of MPTP-treated male C57BL/6 mice. Furthermore, acute Raptor knockout in dopaminergic neurons, which abolishes mTORC1 activity, did not diminish rapamycin's neuroprotective effects, suggesting that its protection is independent of mTORC1 inhibition. Importantly, rapamycin is also a potent inhibitor of FKBP12, a peptidyl-prolyl <em>cis-trans</em> isomerase highly expressed in the brain. Selective knockdown of FKBP12 in nigral dopaminergic neurons confers neuroprotective effects comparable to that of rapamycin, with no synergism observed when the two are combined. Collectively, our results indicate that rapamycin exerts neuroprotective effects in parkinsonian mice through inhibition of FKBP12 rather than mTORC1 signaling. These findings suggest that FKBP12 may serve as a novel target for disease-modifying therapies in PD.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"275 ","pages":"Article 110504"},"PeriodicalIF":4.6,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143936392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"“Maladaptive stress-coping behavior in CX3CR1-deficient mice: Impact of adolescent stress and alcohol exposure on neuroimmune responses and inflammation”","authors":"Dina Medina-Vera ,&nbsp;Laura Martín-Chaves ,&nbsp;Laura Sánchez-Marín ,&nbsp;María Díaz-Ottaviano ,&nbsp;Ana L. Gavito ,&nbsp;Olga Popova ,&nbsp;María José Sánchez-Quintero ,&nbsp;Jorge Rodríguez-Capitán ,&nbsp;Fernando Rodríguez de Fonseca ,&nbsp;Manuel F. Jiménez-Navarro ,&nbsp;Antonia Serrano ,&nbsp;Francisco Javier Pavón-Morón","doi":"10.1016/j.neuropharm.2025.110503","DOIUrl":"10.1016/j.neuropharm.2025.110503","url":null,"abstract":"<div><div>The CX₃CL1/CX₃CR1 chemokine axis regulates synaptic pruning, plasticity, and stress-related behaviors, influencing resilience or vulnerability to psychiatric disorders. Adolescence, a critical period for neuroimmune development, increases susceptibility to stressors. This study investigated how adolescent restraint stress and alcohol exposure affect stress-coping behavior, neuroimmune signaling, and systemic inflammation in adult wild-type (WT) and CX₃CR1 knock-out (KO) mice.</div><div>Eighty-one male and female WT and KO mice were assigned to control (non-stressed, saline-treated), stress (stressed, saline-treated), alcohol (non-stressed, alcohol-treated), and stress + alcohol (stressed, alcohol-treated) groups. Behavioral responses were evaluated using the tail suspension test. Hypothalamic gene expression of CX₃CL1/CX₃CR1, corticotropin-releasing hormone (CRH), and neuropeptide Y (NPY) systems was analyzed alongside plasma corticosterone, adrenocorticotropic hormone (ACTH), CX₃CL1, and inflammatory mediators.</div><div>Adolescent stress—but not alcohol—increased plasma CX₃CL1 levels, which inversely correlated with immobility time in WT mice. KO mice displayed higher baseline immobility than WT mice, whereas stress and/or alcohol paradoxically reduced immobility. These behavioral effects were reproduced by pharmacological inhibition of CX₃CR1. Additionally, KO mice showed disrupted hypothalamic expression of multiple genes in the CRH pathway and <em>Npy1r</em>, attenuated corticosterone responses to stress, and abolished ACTH–corticosterone correlation, suggesting HPA axis dysregulation. KO mice also exhibited exacerbated inflammatory responses to stress and alcohol, including elevated IL-17A/F, IL-11, and IFN-β1 levels.</div><div>CX₃CR1 deficiency disrupts neuroimmune homeostasis, leading to maladaptive stress-coping behaviors and heightened inflammatory reactivity. These findings underscore the protective role of the CX₃CL1/CX₃CR1 axis in neuroinflammatory regulation and stress resilience, supporting CX₃CR1 as a potential therapeutic target in stress-related disorders.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"275 ","pages":"Article 110503"},"PeriodicalIF":4.6,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P2 purinergic signaling and pruritus","authors":"Shipan Liu ,&nbsp;Yuanyuan Zhang ,&nbsp;Guilin Li ,&nbsp;Shangdong Liang","doi":"10.1016/j.neuropharm.2025.110497","DOIUrl":"10.1016/j.neuropharm.2025.110497","url":null,"abstract":"<div><div>Pruritus is a common sensation that triggers scratching. Extracellular nucleotides and nucleosides, along with their receptors, primarily compose the purinergic signaling. The purinergic signaling mechanism in itch remains incompletely understood. Keratinocytes, fibroblasts, Langerhans cells, primary sensory nerve endings in the skin, and neurons and satellite glial cells in primary sensory ganglia (dorsal root ganglia and trigeminal ganglia) have been confirmed to express multiple subtypes of P2X and P2Y receptors. Purinergic signaling in the skin and primary sensory ganglia is involved in the pathological changes of skin pruritus, including atopic dermatitis, psoriasis, systemic sclerosis, diabetes complicated with pruritus, or other pruritus disorders. The interaction between P2 purinergic signaling and histamine receptors, transient receptor potential (TRP) channel receptors, and Mas-related G protein-coupled receptor member A3 (MrgprA3) receptors, which mediate itch signaling, is involved in the pathological process of skin pruritus. P2 purinergic receptor agonists can induce itching behaviors in animals. Targeted antagonism or inhibition of P2 purinergic receptors in the skin and primary sensory ganglia can alleviate pathological changes in skin pruritus. This review summarizes studies concluding that P2 receptors are involved in the pathogenesis of pruritus, with several showing potential as novel therapeutic options for alleviating pruritus.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"275 ","pages":"Article 110497"},"PeriodicalIF":4.6,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143923776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The biased OTR ligands -atosiban and carbetocin- differentially inhibit early or late formalin-induced nociception in rats","authors":"Antonio Espinosa de los Monteros-Zúñiga ,&nbsp;Jorge Luis Almazán ,&nbsp;Guadalupe Martínez-Lorenzana ,&nbsp;Mónica C. Guillen-Paredes ,&nbsp;G. Aleph Prieto ,&nbsp;Miguel Condés-Lara ,&nbsp;Abimael González-Hernández","doi":"10.1016/j.neuropharm.2025.110487","DOIUrl":"10.1016/j.neuropharm.2025.110487","url":null,"abstract":"<div><div>Males are more sensitive to intrathecal oxytocin-induced antinociception than females. This antinociception has been linked to oxytocin receptor (OTR) activation. Canonically, OTR is coupled to Gq but can also activate Gi/o proteins. In males, the formalin test showed that oxytocin prevented early nociception (flinches) via the Gq pathway, whereas long-lasting hypersensitivity was halted by Gi/o activation. Here, we tested the effects of biased OTR ligands carbetocin (Gq) and atosiban (Gi/o) on formalin-induced nociception in male and female Wistar rats. Specifically, we assessed the effects of intrathecal carbetocin and atosiban on early (flinches) and late (paw withdrawal threshold) formalin-induced nociception. Pretreatment with L-368,899 (OTR antagonist), U-73122 (phospholipase C inhibitor), L-NAME (nitric oxide synthase inhibitor), or <em>pertussis</em> toxin (a Gi/o inhibitor) was used to dissect the pathways involved. Furthermore, late activation of Akt, ERK1/2, and S6 ribosomal (S6) protein was tracked in spinal tissue by immunoblotting. Carbetocin prevented early nociception in males, whereas atosiban precluded late nociception in both sexes. The antinociception induced by carbetocin and atosiban was abolished by L-368,899, pointing out the role of OTR. Pretreatment with U-73122 or L-NAME blocked the carbetocin effect, whereas <em>pertussis</em> toxin prevented the atosiban effect. Late hypersensitivity correlated with increased levels of phosphorylated S6 protein in the spinal tissue, an effect partly blocked by atosiban. These data suggest that carbetocin prevents early nociception in males via OTR-Gq, and atosiban blocks late hypersensitivity in both sexes via OTR-Gi/o, implying that OTR-biased activation underlies the sexual dimorphism observed in oxytocin-induced antinociception.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"275 ","pages":"Article 110487"},"PeriodicalIF":4.6,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143929449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amphetamine increases timing variability by degrading prefrontal temporal encoding","authors":"Matthew A. Weber,&nbsp;Kartik Sivakumar,&nbsp;Braedon Q. Kirkpatrick,&nbsp;Hannah R. Stutt,&nbsp;Ervina E. Tabakovic,&nbsp;Alexandra S. Bova,&nbsp;Young-cho Kim,&nbsp;Nandakumar S. Narayanan","doi":"10.1016/j.neuropharm.2025.110486","DOIUrl":"10.1016/j.neuropharm.2025.110486","url":null,"abstract":"<div><div>Amphetamine is a commonly abused psychostimulant that increases synaptic catecholamine levels and impairs executive functions. However, it is unknown how acute amphetamine affects brain areas involved in executive control, such as the prefrontal cortex. We studied this problem in mice using interval timing, which requires participants to estimate an interval of several seconds with a motor response. Rodent prefrontal cortex ensembles are required for interval timing. We tested the hypothesis that amphetamine disrupts interval timing by degrading prefrontal cortex temporal encoding. We first quantified the effects of amphetamine on interval timing performance by conducting a meta-analysis of 15 prior rodent studies. We also implanted multielectrode recording arrays in the dorsomedial prefrontal cortex of 7 mice and then examined the effects of 1.5 mg/kg <em>D-</em>amphetamine injected intraperitoneally on interval timing behavior and prefrontal neuronal ensemble activity. A meta-analysis of previous literature revealed that amphetamine produces a large effect size on interval timing variability across studies but only a medium effect size on central tendencies of interval timing. We found a similar effect on interval timing variability in our task, which was accompanied by greater trial-to-trial variability in prefrontal ramping, attenuated interactions between pairs of ramping neurons, and dampened low-frequency oscillations. These findings suggest that amphetamine alters prefrontal temporal processing by increasing the variability of prefrontal temporal encoding. Our work provides insight into how amphetamine affects prefrontal activity, which may be useful in developing new neurophysiological markers for amphetamine use and novel treatments targeting the prefrontal cortex.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"275 ","pages":"Article 110486"},"PeriodicalIF":4.6,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143936391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of anoctamin-1 calcium-activated chloride channels reduces voluntary alcohol consumption in rats","authors":"Gleice Kelli Silva-Cardoso,&nbsp;Prosper N'Gouemo","doi":"10.1016/j.neuropharm.2025.110498","DOIUrl":"10.1016/j.neuropharm.2025.110498","url":null,"abstract":"<div><div>Repeated episodes of binge drinking can lead to an alcohol use disorder, yet the underlying pharmacological mechanisms are still not fully understood. Nevertheless, emerging evidence indicates that Ca²⁺-dependent signaling effectively reduces alcohol consumption without affecting water intake. Therefore, activating anoctamin1 (ANO1), a Ca²⁺-activated chloride channel and a component of Ca²⁺-dependent signaling, can similarly decrease alcohol drinking while maintaining normal water intake. This study investigates how activation of ANO1 channels with EACT affects voluntary alcohol consumption in male and female Sprague-Dawley rats using the intermittent alcohol access method in a two-bottle choice paradigm. Rats were trained to drink 7.5 % ethanol or water for four weeks before administering either EACT (2.5, 5, and 10 mg/kg). Afterward, their alcohol intake, preference, and water intake were systematically recorded 2 and 24 h after exposure to water and 7.5 % ethanol solution. The results indicated that female rats consumed more alcohol than males. Furthermore, activating ANO1 channels with EACT significantly decreased alcohol intake and preference in males, only at the 5 mg/kg dose; in females, this effect was observed as a linear response at both the 5 and 10 mg/kg doses, highlighting distinct sex-related differences. Additionally, the inhibitory effect of EACT on alcohol consumption was associated with increased water intake in females, suggesting a potential influence of EACT on thirst homeostasis. Collectively, these findings highlight the differential effects of EACT on alcohol intake, preference, and water intake based on sex, and underscore the complexity of consummatory behavior mechanisms.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"275 ","pages":"Article 110498"},"PeriodicalIF":4.6,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143923777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of the neurotensin signaling system on feeding and satiety","authors":"Katie D. Thompson ,&nbsp;Gina M. Leinninger","doi":"10.1016/j.neuropharm.2025.110496","DOIUrl":"10.1016/j.neuropharm.2025.110496","url":null,"abstract":"<div><div>Neurotensin (Nts) is a peptide that acts via neurotensin receptors and is implicated in multiple aspects of physiology and behavior, including modulating feeding and body weight. How and where the Nts signaling system mediates these effects, and via which of its receptor isoforms is incompletely understood. This review examines the role of Nts signaling via the periphery and central nervous system on feeding and body weight. These data highlight various ways in which the Nts system contributes to feeding and body weight that differ depending on the site, tissue, and the Nts or Nts receptor-expressing cell type in question. Given that the Nts system does not convey the same signaling throughout the body, constitutive approaches modulating the expression or signaling of the Nts signaling system may not provide sufficient resolution to reveal how it impacts feeding. Combining neuropharmacology and site-specific approaches holds promise define the broad range of mechanisms by the Nts system modulates feeding and satiety and its contributions to normal and disrupted feeding states.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"275 ","pages":"Article 110496"},"PeriodicalIF":4.6,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143943773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preventive effect of a garlic compound on astrocyte-mediated neuroinflammation in Parkinson's disease","authors":"Jaeheon Seol ,&nbsp;Jaehoon Kim ,&nbsp;Sung Min Moon ,&nbsp;Duwon Jung ,&nbsp;Changyu Kang ,&nbsp;Ki Wung Chung ,&nbsp;Young-Suk Jung ,&nbsp;Young-Hwa Chung ,&nbsp;Yunjin Jung ,&nbsp;Hae Young Chung ,&nbsp;Seung-Cheol Chang ,&nbsp;Jaewon Lee","doi":"10.1016/j.neuropharm.2025.110494","DOIUrl":"10.1016/j.neuropharm.2025.110494","url":null,"abstract":"<div><div>Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuron loss and resultant severe motor dysfunction. While current treatments primarily focus on maintaining dopamine levels, effective targeting of neuroinflammation, an important driver of disease progression, remains an unmet need. This study investigates the neuroprotective potential of BMDA (BMDA(N-benzyl-N-methyldecan-1-amine)), a natural compound derived from garlic with strong anti-inflammatory properties, using an MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced mouse model of PD. Behavioral assessments, immunohistochemistry, and dopamine analysis showed that BMDA effectively reduced neuroinflammation and preserved dopaminergic neurons. <em>In vitro</em> studies showed that BMDA significantly suppressed inflammatory markers and reduced astrocyte activation in MPP⁺-induced primary cultured astrocytes, and real-time PCR confirmed that BMDA attenuated proinflammatory cytokines and chemokines. Further mechanistic studies showed that BMDA inhibited the p-p65 and p-ERK signaling pathways, which underlie astrocyte-mediated neuroinflammation. These findings suggest that BMDA should be considered a therapeutic candidate for PD that targets neuroinflammation.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"275 ","pages":"Article 110494"},"PeriodicalIF":4.6,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143912202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sirtuins modulators mitigate hypoxia-induced cell death due to changes in histone 3 acetylation, and mitochondrial function, dynamics, and content","authors":"Luiz Felipe Souza e Silva ,&nbsp;Amanda Siena ,&nbsp;Jessica Mayumi Yuzawa ,&nbsp;Tatiana Rosado Rosenstock","doi":"10.1016/j.neuropharm.2025.110484","DOIUrl":"10.1016/j.neuropharm.2025.110484","url":null,"abstract":"<div><div>Hypoxia is a key environmental factor linked to neurodevelopmental complications, primarily through its impact on mitochondrial dysfunction. Given that sirtuins regulate mitochondrial and cellular metabolism, we aimed to investigate whether pharmacological modulation of sirtuins could protect neurons from hypoxia-induced mitochondrial dysfunction and cell death. To explore this, primary cortical neurons from male Wistar rats (control) and Spontaneously Hypertensive Rats (a model for neonatal hypoxia and schizophrenia) were exposed to cobalt chloride (CoCl₂) to chemically induce hypoxia. Neurons were also treated with Nicotinamide (50 μM), Resveratrol (0.5 μM), and Sirtinol (5 μM) to modulate sirtuin activity. We first assessed histone deacetylation, cell death, mitochondrial calcium retention capacity, mitochondrial membrane potential, and levels of reactive oxygen species (ROS). In addition, we analysed the expression of genes related to mitochondrial metabolism, dynamics, and biogenesis, as well as high-energy compound levels. Our data indicate that both chemical and neonatal hypoxia caused mitochondrial depolarization, reduced calcium retention, increased ROS levels, and elevated <em>Nfe2l2</em> expression in primary cortical neurons. Hypoxia also led to increased expression of genes associated with mitochondrial biogenesis and fission, as well as reduced ATP levels and elevated pyruvate and lactate levels. Importantly, treatment with sirtuin modulators enhanced neuron viability, likely by further increasing <em>Nfe2l2</em> expression and reducing ROS production. These modulators also improved metabolic outcomes, including higher ATP levels, and normalised pyruvate and lactate production, as well as mitochondrial fusion gene expression. Collectively, our findings suggest that sirtuin modulators could mitigate hypoxia-induced damage and may represent a potential therapeutic strategy for managing neurodevelopmental disorders.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"275 ","pages":"Article 110484"},"PeriodicalIF":4.6,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143923782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sleep deprivation modulates pain sensitivity through alterations in lncRNA and mRNA expression in the nucleus accumbens and ventral midbrain","authors":"Kai-Li Wang ,&nbsp;Wei-Sen Gao ,&nbsp;Abdul Nasir ,&nbsp;Yuan-Fang Wang ,&nbsp;Meng Yuan ,&nbsp;Zhen-Zhen Zhang ,&nbsp;Qian Bai ,&nbsp;Zhi-Song Li","doi":"10.1016/j.neuropharm.2025.110485","DOIUrl":"10.1016/j.neuropharm.2025.110485","url":null,"abstract":"<div><div>Sleep deprivation (SD) is a growing public health concern with implications for pain sensitivity and well-being. Although the relationship between sleep and pain is well understood, the underlying mechanisms remain largely unknown. This study investigates how SD influences pain sensitivity by modulating gene expression in the nucleus accumbens (NAc) and ventral tegmental area (VTA) of mice. Using the CPW sleep deprivation model, mice were deprived of sleep for three days, simulating preoperative conditions. Behavioral tests revealed heightened mechanical and thermal hypersensitivity post-SD. Brain MRI, immunofluorescence, and RNA sequencing analyses showed significant changes in the expression of non-coding RNAs (ncRNAs) and mRNAs in NAc and VTA, implicating several pain-related genes. Functional enrichment analysis highlighted pathways associated with neurotransmission, inflammation, and stress response. The study identified <em>Hcrt</em> and <em>Apoe</em> as critical modulators of SD-induced hyperalgesia, with potential therapeutic implications for managing pain associated with SD. Findings suggest that overlapping pathways exist between sleep and pain sensitivity, offering insights into the molecular mechanisms that connect sleep disorders with heightened pain responses.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"275 ","pages":"Article 110485"},"PeriodicalIF":4.6,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}