Neuropharmacology最新文献

{"title":"Kcc-ReHo and Cohe-ReHo in bipolar disorder: their associated genes and potential for diagnosis and treatment prediction","authors":"Dan Lv ,&nbsp;Hao-hao Yan ,&nbsp;Chun-guo Zhang ,&nbsp;Xiao-ling Li ,&nbsp;Le-yi Zhang ,&nbsp;Jia-quan Liang ,&nbsp;Chao-hua Tang ,&nbsp;Wei-bin Wu ,&nbsp;Wen Deng ,&nbsp;Guo-jun Xie ,&nbsp;Wen-bin Guo","doi":"10.1016/j.neuropharm.2025.110575","DOIUrl":"10.1016/j.neuropharm.2025.110575","url":null,"abstract":"<div><div>The neural mechanisms underlying resting-state cerebral functional activity in bipolar disorder (BD) and the effects of pharmacotherapy on it remain unclear. This study investigated changes in local brain activity in BD patients (BDPs) following treatment, evaluated the diagnostic and prognostic potential of regional homogeneity (ReHo), and explored associated genes and biological processes. Resting-state fMRI data and clinical variables were collected from 68 BDPs (at baseline and after 3 months of pharmacotherapy) and 80 healthy controls (HCs). Local brain activity was assessed using Kendall's coefficient of concordance ReHo (KCC-ReHo) and Coherence ReHo (Cohe-ReHo). Support Vector Machine (SVM) and Support Vector Regression (SVR) were employed for classification and treatment response prediction. Neuroimaging-transcriptomic analysis was conducted to explore the relationship between altered ReHo and gene expression profiles from the Allen Human Brain Atlas. BDPs exhibited greater KCC-ReHo and Cohe-ReHo values in the striatum and cerebellum circuit, but lower values in the prefrontal cortex compared to HCs. Following pharmacotherapy, KCC-ReHo values in the cerebellum circuit decreased. Classification accuracy was 68 % (AUC: 0.76 and 0.75 for KCC-ReHo and Cohe-ReHo, respectively), with predicted treatment response moderately correlating with actual outcomes (<em>r</em> = 0.34 and 0.31). Twenty-seven genes were found to be associated with ReHo group differences. Our findings underscore the dysfunction of the prefrontal-striatum and cerebellar circuits as key neuropathological mechanisms in BD. The observed reduction in cerebellar activity post-pharmacotherapy suggests a potential therapeutic mechanism, while neuroimaging-transcriptomic analysis highlights the genetic underpinnings of these alterations in BDPs.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"278 ","pages":"Article 110575"},"PeriodicalIF":4.6,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144502329","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":"Neuroprotective potential of novel CARTp analogs in the hippocampus of THY-Tau22 mouse model of Tau pathology","authors":"Vilém Charvát ,&nbsp;Petra Vaculová ,&nbsp;Blanka Železná ,&nbsp;Lenka Maletínská ,&nbsp;Andrea Pačesová","doi":"10.1016/j.neuropharm.2025.110578","DOIUrl":"10.1016/j.neuropharm.2025.110578","url":null,"abstract":"<div><div>Anorexigenic neuropeptides have shown a remarkable potential in the treatment of neurodegenerative disorders, such as Alzheimer's disease (AD). One of the strong anorexigenic neuropeptides is called cocaine- and amphetamine-regulated transcript peptide (CARTp), which is the third most abundant transcript in the hypothalamus. Previously, we introduced a novel palmitoylated analog of 2-SS-CART(61–102), a specific analog of natural CART(61–102) with two disulfide bridges, with anorexigenic and neuroprotective properties. This study explores the impact of 2-SS-CART(61–102) and its palmitoylated analog, palm-2-SS-CART(61–102), on the early progression of Tau pathology characteristic of AD, utilizing the THY-Tau22 transgenic mouse model. Chronic subcutaneous treatment with CARTp analogs improved short-term spatial memory in the Y-maze, reduced the number of neurofibrillary tangles (NFT) in the hippocampal CA1 region, and decreased the level of GFAP + astrocytes in the hippocampus of THY-Tau22 mice. Furthermore, treatment with CARTp analogs showed increased levels of synaptic markers in the hippocampus. A beneficial effect on these attributes makes CARTp analogs promising for AD therapy.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"278 ","pages":"Article 110578"},"PeriodicalIF":4.6,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144510743","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":"Temporal and spatial patterns of secondary motor cortex calcium activity in cocaine self-administration: A study using miniScope imaging and machine learning","authors":"Amith Korada ,&nbsp;Yingying Chen ,&nbsp;Ziqian Bi ,&nbsp;Haoying Fu ,&nbsp;Michal A. Lange ,&nbsp;Joreylis Michelle F. Montgomery ,&nbsp;Chandrashekar Rayanki ,&nbsp;Changyong Guo ,&nbsp;Shiaofen Fang ,&nbsp;Yao-Ying Ma","doi":"10.1016/j.neuropharm.2025.110574","DOIUrl":"10.1016/j.neuropharm.2025.110574","url":null,"abstract":"<div><div>Addiction is a chronic mental disorder caused by disruptions in brain function. While most research has focused on the medial prefrontal cortex, our recent findings highlight the secondary motor cortex (M2) as a key region modulating cocaine-seeking behaviors during relapse. Mechanisms underlying the role of M2 in addiction remain unclear. We hypothesize that initial drug-taking behaviors directly reshape M2 neuronal activity. This study investigated the effects of five 1-hr daily intravenous self-administration (IVSA) sessions on M2 neuronal activity in male C57BL/6J mice using <em>in vivo</em> Ca²⁺ imaging <em>via</em> miniScopes. Temporal and spatial patterns of Ca²⁺ transients were analyzed across three IVSA factors: IV substance (i.e., saline <em>vs</em>. cocaine), IVSA days, and within-session stages. Machine learning models, including Recurrent Neural Networks for temporal patterns, and Neural Networks, Support Vector Machines, and Extreme Gradient Boosting for spatial patterns, were employed.</div></div><div><h3>Results</h3><div>Cocaine-treated mice displayed consistent drug-taking behaviors within sessions and increased intake on Day 5 compared to Day 1, unlike saline-treated mice, which showed reduced operant behaviors within each daily session. IV substance was the most sensitive factor influencing both temporal and spatial patterns of M2 Ca²⁺ transients, characterized by frequency and frequency-amplitude interactions, but not amplitude alone. A 15-s bin size optimized differentiation between saline and cocaine groups.</div></div><div><h3>Conclusion</h3><div>Both temporal and spatial alterations in M2 neuronal activity were detected during early cocaine exposure, revealing early changes that may contribute to later drug relapse. These findings underscore the importance of advanced imaging and machine learning techniques in advancing addiction research.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"278 ","pages":"Article 110574"},"PeriodicalIF":4.6,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512185","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":"Bioinformatics and validation reveal spinal cord cathepsin S potential degradation of perineuronal nets in neuropathic pain","authors":"Jiahui Pang ,&nbsp;Ziwei Hu ,&nbsp;Yubai Zhao ,&nbsp;Xinli Liu ,&nbsp;Bo Wang ,&nbsp;Qian Fang ,&nbsp;Yin Xu ,&nbsp;Yingxuan Hu ,&nbsp;Hui Zeng ,&nbsp;Wen Wu","doi":"10.1016/j.neuropharm.2025.110577","DOIUrl":"10.1016/j.neuropharm.2025.110577","url":null,"abstract":"<div><div>Neuropathic pain (NP), resulting from nerve damage or diseases, significantly impacts patients’ quality of life. Bioinformatics analysis can assist researchers in identifying key molecular pathways involved disease progression. This study aims to investigate the hub genes in the spinal cord of NP rats, with a particular focus on the relationship between Cathepsin S (CTSS) and perineuronal nets (PNNs). Bioinformatics analysis identified <em>Ctss</em> as a hub gene in NP dataset GSE18803. After injury, CTSS expression was significantly upregulated in the spinal cord of NP rats, and the immunofluorescence staining confirmed the degradation of PNNs in the ipsilateral spinal cord lamina V of NP rats. Furthermore, in vitro experiment demonstrated that CTSS promoted the degradation of PNNs. Finally, knockdown CTSS expression spinal cord relived pain and PNNs degradation in NP rats. These findings suggest that CTSS is upregulated in the spinal cord of NP rats and reveal CTSS potential degradation of PNNs.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"278 ","pages":"Article 110577"},"PeriodicalIF":4.6,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507098","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":"Hydroxysafflor yellow A attenuates the blood-brain barrier dysfunction and neuroinflammation through anti-inflammatory microglial polarization after intracerebral hemorrhage","authors":"Fei Zheng ,&nbsp;Xiaohang Guo ,&nbsp;Qiuju Yan ,&nbsp;Yaya Zhou ,&nbsp;En Hu ,&nbsp;Haonan Zhu ,&nbsp;Menghan Cheng ,&nbsp;Zhe Yu ,&nbsp;Mingrui Hu ,&nbsp;Ruoqi Ding ,&nbsp;Haigang Li ,&nbsp;Wei Zhang ,&nbsp;Tao Tang ,&nbsp;Yang Wang ,&nbsp;Teng Li ,&nbsp;Changqing Deng","doi":"10.1016/j.neuropharm.2025.110576","DOIUrl":"10.1016/j.neuropharm.2025.110576","url":null,"abstract":"<div><div>The destruction of the blood-brain barrier (BBB) is the most common life-threatening event of intracerebral hemorrhage (ICH). Balancing microglia polarization is a prospective therapeutic strategy for BBB injury. This study aims to explore the neuroprotective effects and the underlying mechanisms of Hydroxysafflor yellow A (HSYA) from the perspective of BBB disruption and neuroinflammation. ICH was induced by intracerebral injection of collagenase Ⅶ in C57BL/6J male mice, and HSYA was injected through the tail vein for three days. We established three oral concentrations for HSYA and found that the administration of HSYA (20 mg/kg/d) significantly improved the neurological deficits of ICH mice and reversed the histopathological damage of the brain. Using IgG and Evans Blue staining, we demonstrated that HSYA prominently facilitated the BBB repair after ICH with no bleeding risk. HSYA greatly enhanced the expression of tight junction proteins (ZO-1, occludin, and claudin-5) but decreased MMP9. HSYA also significantly reduced the CD68⁺ microglia with pro-inflammation mediators (IL-1β, IL-6, TNF-α, iNOS, HO-1, and COX2) and increased the Arg-1⁺ microglia with anti-inflammation mediators (IL-10, and TGF-β). We identified the PI3K/Akt signaling pathway through database mining and bioinformatics analysis and verified the activation of PI3K/Akt by HSYA intervention. Further, employing the PI3K-specific antagonist LY294002 confirmed that the pre-administration of LY294002 mostly negated the neuroprotective effects of HSYA. HSYA activates the PI3K/Akt/mTOR signaling pathway, balancing microglial polarization and improving BBB integrity, highlighting its potential to be an effective drug option for ICH treatment.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"278 ","pages":"Article 110576"},"PeriodicalIF":4.6,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144490880","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":"Irisin ameliorates cognitive impairment in a lipopolysaccharide-induced neuroinflammation mouse model by inhibiting the NLRP3 inflammasome pathway in microglia","authors":"Da-Qi Zhang ,&nbsp;Ge Li ,&nbsp;Zong-Dong Fu ,&nbsp;Yu-Sheng Huang ,&nbsp;Xiao-Li Feng ,&nbsp;Li-Jun Chen ,&nbsp;Rong Wang ,&nbsp;Wen-Jie Zhao ,&nbsp;Qifu Li","doi":"10.1016/j.neuropharm.2025.110572","DOIUrl":"10.1016/j.neuropharm.2025.110572","url":null,"abstract":"<div><div>Neuroinflammation is implicated in the development of neurodegenerative diseases. Irisin was first identified as an exercise-induced skeletal muscle-secreted glycosylated protein. The main physiological functions of irisin were initially thought to include the promotion of angiogenesis; improvement of oxidative metabolism; and regulation of glucose, lipid, and mitochondrial metabolism. However, despite its demonstrated neuroprotective effects in Alzheimer's disease, the precise role of irisin in neuroinflammation, particularly in lipopolysaccharide (LPS)-induced cognitive impairment, remains unclear. This study was performed to investigate the protective effects and mechanisms of irisin on LPS-induced inflammatory cognitive impairment both <em>in vivo</em> and <em>in vitro</em>. We induced cognitive impairment in mice using LPS and evaluated cognitive function by employing the Morris water maze test. Further, we used immunofluorescence staining and flow cytometry to assess microglial activation and polarization in the cortex and hippocampus, two brain regions involved in cognitive behaviors. Western blotting was used to detect the levels of proteins related to the NLRP3 signaling pathway. Furthermore, we measured tumor necrosis factor -α, interleukin (IL)-6, CCL2, IL-4 and IL-10 levels in BV2 cells using a mouse enzyme-linked immunosorbent assay kit and characterized M1 and M2 polarization using flow cytometry. Irisin administration improved learning and cognitive abilities but inhibited microglial activation and M1 polarization in LPS-treated mice. Irisin significantly decreased the expression of NLRP3 inflammasome signaling pathway molecules in LPS-treated mice. Further, irisin suppressed microglial activation and reduced the production of proinflammatory cytokines in BV2 cells. Moreover, irisin protected PC12 cells from LPS-activated BV2 microglia-induced neurotoxicity and inhibited apoptosis in PC12 cells induced by BV2 conditioned medium. Irisin mitigated inflammatory cognitive dysfunction and suppressed microglial activation and M1-type polarization by inhibiting the NLRP3 signaling pathway.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"278 ","pages":"Article 110572"},"PeriodicalIF":4.6,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144366882","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":"Blocking IL-17A inhibits methamphetamine-induced hyperlocomotion and conditioned place preference and prevents methamphetamine abstinence-induced depression-like behaviors in mice","authors":"Saadet Inan ,&nbsp;Sonita Wiah ,&nbsp;Alexandra Szmacinski ,&nbsp;Scott Dunn ,&nbsp;Joseph J. Meissler ,&nbsp;Ekaterina K. Koltsova ,&nbsp;Sergey Grivennikov ,&nbsp;Scott M. Rawls","doi":"10.1016/j.neuropharm.2025.110571","DOIUrl":"10.1016/j.neuropharm.2025.110571","url":null,"abstract":"<div><div>We demonstrated previously that blocking IL-17A, a proinflammatory cytokine, prevents oxycodone-induced depression-like effects and anxiety-like effects during abstinence from MDPV (a psychostimulant) in rats. Here, we tested the hypothesis that eliminating IL-17A signaling (pharmacological antagonism using IL-17A Ab or genetic deletion of IL-17RC) would inhibit behavioral and neurochemical effects elicited by methamphetamine (METH) exposure and abstinence in adult mice. We investigated rewarding and locomotor-activating effects of METH and withdrawal-induced anxiety- and depression-like effects during METH abstinence. Mice received saline or METH (5 mg/kg, IP) once daily for 18 d. Locomotion was measured on days 1 and 15. Anxiety- and depression-like effects were investigated 72 and 96 h after the last METH injection using the elevated plus maze and forced swim test, respectively. IL-17A antibody (Ab, 60 μg/100 μl, IP) was injected every 3rd day of METH exposure. METH-induced hyperlocomotion was significantly reduced in IL-17RC knockout mice or by treatment with the IL-17A Ab (100 μg/100 μl). Neutralization of IL-17A or genetic deletion of IL-17RC prevented development of depression-like effects during METH abstinence. Also, mRNA levels of IL-17RC, but not IL-17RA, in the NAC were enhanced during METH abstinence. Development of METH conditioned place preference (CPP) was prevented by IL-17A Ab but was not affected by IL-17RC deletion in mice conditioned with METH (3 mg/kg) for 4 d. Our data show that abolishing IL-17A signaling reduces METH-induced hyperlocomotion and CPP and attenuates depression-like effects during METH abstinence. These results highlight studying IL-17A blockade as a neuroimmune-based approach to mitigate METH adverse effects.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"278 ","pages":"Article 110571"},"PeriodicalIF":4.6,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144366881","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":"Intrinsic activation of the coagulation pathway induces mouse sciatic nerve hypoexcitability","authors":"Shani Berkowitz ,&nbsp;Valery Golderman ,&nbsp;Zehavit Goldberg ,&nbsp;Joab Chapman ,&nbsp;Amir Dori ,&nbsp;Nicola Maggio ,&nbsp;Jérôme Joël Devaux ,&nbsp;Efrat Shavit-Stein","doi":"10.1016/j.neuropharm.2025.110569","DOIUrl":"10.1016/j.neuropharm.2025.110569","url":null,"abstract":"<div><h3>Background</h3><div>Thrombin and its protease-activated receptor 1 (PAR1) modulate neuronal function in experimental settings, but the effects of activating intrinsic neuronal coagulation factors remain unclear. We investigated how activation of this pathway influences peripheral nerve function in an isolated mouse sciatic nerve model.</div></div><div><h3>Methods</h3><div>We used an <em>ex vivo</em> mouse sciatic nerve model to evaluate the effects of coagulation activation on neural excitability. Isolated nerves from male C57BL/6J mice were treated with Russell's viper venom factor X (FX) activator (RVV-X, 0.3 U/ml), FX inhibitor (apixaban, 1 μM), thrombin (200 U/ml), or a PAR1 antagonist (SCH 79797, 1 μM). Electrophysiological recordings assessed evoked neural responses. Thrombin and FX activity were quantified in tissue and artificial cerebrospinal fluid (aCSF). mRNA and immunofluorescence analyses localized coagulation-related components.</div></div><div><h3>Results</h3><div>RVV-X and thrombin treatments significantly attenuated neural responses to repeated stimulation (p &lt; 0.0001), while apixaban and the PAR1 antagonist prevented these effects (p &gt; 0.9999). RVV-X markedly increased thrombin activity in aCSF (p &lt; 0.0001). mRNA and immunofluorescence analyses confirmed that coagulation-related components were primarily expressed in the paranodal region of the sciatic nerve.</div></div><div><h3>Conclusions</h3><div>The FX-thrombin pathway is intrinsically present and functionally active in sciatic nerves of mice. Activation of this pathway reduces neuronal excitability via PAR1, suggesting a finely tuned feedback mechanism between coagulation factors and neural function. These findings highlight the potential role of coagulation-mediated mechanisms in peripheral nerve pathologies, which may serve as biomarkers and therapeutic targets for neurological diseases.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"278 ","pages":"Article 110569"},"PeriodicalIF":4.6,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476124","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":"Histaminergic transmission potentiates post-traumatic stress-induced expression of anxiety in mice","authors":"Vaibhav Maturkar,&nbsp;Richa Patel,&nbsp;Chhatrapal Patel,&nbsp;Venu Anand Das Vaishnav,&nbsp;Nishant Sudhir Jain","doi":"10.1016/j.neuropharm.2025.110564","DOIUrl":"10.1016/j.neuropharm.2025.110564","url":null,"abstract":"<div><div>Post-traumatic stress is associated with an increased expression of anxiety traits and is reported to be accompanied by altered brain histamine content. However, the contribution of the central histaminergic system in the stress induced anxiety, still remains unclear. Therefore, the present study explored the plausible role of central histaminergic transmission in stress-induced anxiety measures in mice using LDB test and in the expression of CORT, CREB, or BDNF levels in the whole brain, PFC, amygdala, and hippocampus of mice. The mice were exposed to the SPS protocol and subsequently left undisturbed for 7 days. On the 8th day, non-SPS/SPS exposed mice were treated i.c.v with histaminergic agents such as histamine, or histamine precursor, l-histidine, H₁ agonist, FMPH, H₂ agonist, amthamine, H₁ antagonist, cetirizine or H₂ antagonist, ranitidine or H₃ inverse agonist, thioperamide and thereafter evaluated for changes in expression of anxiety followed by estimation of CORT, CREB and BDNF levels in brain. Results revealed that SPS-exposed mice elicit heightened anxiety-like behavior accompanied by increased levels of blood or brain histamine and CORT with reduced BDNF/CREB expression in the all-brain tissues. Administration of histaminergic enhancing agents to SPS-exposed mice potentiated the higher expression of anxiety, also further enhanced CORT, and diminished the BDNF/CREB expression in all brain regions. Conversely, central injection of the H₁ receptor antagonist, cetirizine (0.1 μg/mouse) or H₂ receptor antagonist, ranitidine (10 μg/mouse, i.c.v) to SPS mice completely alleviated all the stressed induced changes while H₃ receptor inverse agonist, thioperamide (2, 10 μg/mouse) failed to affect CORT but restored basal anxiety, CREB and BDNF expression. Thus, the blockade of central histamine H₁/H₂/H₃ receptors might mitigate SPS-induced anxiety-like manifestations by extenuating the SPS-induced CORT, CREB, and BDNF expression.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"278 ","pages":"Article 110564"},"PeriodicalIF":4.6,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476123","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":"Adolescent nutritional influences on the brain: implications for eating behaviors","authors":"Mary Lazzaro ,&nbsp;Austin M. Mills ,&nbsp;Emily E. Noble","doi":"10.1016/j.neuropharm.2025.110570","DOIUrl":"10.1016/j.neuropharm.2025.110570","url":null,"abstract":"<div><div>Adolescence represents a life stage in which vast physiological and neuroendocrine changes contribute to rapid growth and development. Throughout this transition from childhood to adulthood, the adolescent brain is in a critical developmental period. This is especially true for the prefrontal cortex and hippocampus, essential areas for executive functioning. The formation of lasting synaptic connections and dynamic plasticity within the adolescent brain make it especially vulnerable to environmental insults, such as a poor-quality diet. Herein, we review research pertaining to the period of adolescence with respect to food intake control as well as the impact of the modern food environment on the development of the prefrontal cortex and hippocampus and discuss implications for ingestive behaviors throughout rest of life.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"278 ","pages":"Article 110570"},"PeriodicalIF":4.6,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144369100","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}