Neuropharmacology最新文献

{"title":"Neuropeptide S system mediates nicotine-induced reward-facilitatory behavior","authors":"Harish M. Kawade ,&nbsp;Utkarsh P. Patil ,&nbsp;Deepali M. Pandhare ,&nbsp;Nishikant K. Subhedar ,&nbsp;Dadasaheb M. Kokare","doi":"10.1016/j.neuropharm.2025.110543","DOIUrl":"10.1016/j.neuropharm.2025.110543","url":null,"abstract":"<div><div>Neuropeptide S (NPS), a 20-amino acid bioactive molecule has emerged as a promising treatment target for substance abuse in preclinical research. However, its role in nicotine reward, a major contributor to tobacco addiction, remains unexplored. This study investigated the involvement of the NPS system in reward-related effects of nicotine using the intracranial self-stimulation (ICSS) procedure in operant chamber. Adult male Wistar rats were implanted with bipolar electrode targeting the lateral hypothalamus-medial forebrain bundle and trained under a fixed-ratio 1 schedule across a range of brain stimulation frequencies (165-33 Hz). Under control conditions, the trained rats displayed a frequency-dependent increase in lever-press activity. Intracerebroventricular (i.c.v.) infusion of NPS (0.5–2 nmol) facilitated ICSS behaviour, while NPS receptor antagonist SHA-68 (0.1–10 nmol) was not effective. However, SHA-68 pretreatment (i.c.v.) dose dependently blocked the ICSS-facilitatory action of nicotine (0.25 mg/kg; subcutaneous, s.c.). A single nicotine injection (s.c.) activated NPS-containing neurons in the pericoerulear area (peri-LC), and increased NPS protein levels in the lateral hypothalamus (LH). Repeated nicotine administration (s.c.) elevated NPS mRNA expression in the peri-LC, and increased protein levels in the LH, paraventricular thalamus and peri-LC. However, these changes seem region specific since the nicotine treatment, in single or multiple doses, ensued no response in parabrachial nucleus, amygdala or ventral tegmental area. In sum, we suggest that the endogenous NPS system plays a critical role in reward-related effects of nicotine.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"278 ","pages":"Article 110543"},"PeriodicalIF":4.6,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144223131","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":"Unlocking molecular secrets: The role of miRNAs in Parkinson's disease dynamics","authors":"Rehab A. Ismail ,&nbsp;Mohamed Abobakr ,&nbsp;Mostafa Mohamed ,&nbsp;Ahmed Hussieny ,&nbsp;Mohamed Alaa ,&nbsp;Mostafa tarek ,&nbsp;Shereen Saeid Elshaer","doi":"10.1016/j.neuropharm.2025.110542","DOIUrl":"10.1016/j.neuropharm.2025.110542","url":null,"abstract":"<div><div>Parkinson's disease (PD) is a devastating neurological age-related ailment that causes dysfunction in the motor system, leading to symptoms such as involuntary shaking at rest, muscle stiffness with jerky movements, difficulty with walking, sluggish movement, and issues in sustaining posture. A state of insufficient dopamine in the striatum can be linked to a significant decrease in dopaminergic neurons within the substantia nigra pars compacta. Likewise, the formation of Lewy bodies is a distinctive pathogenic feature of PD. Although contemporary therapeutic strategies for PD focus on preserving dopaminergic neurons or restoring dopamine levels in the brain, it is crucial to recognize that achieving total remission of the illness is still inaccessible. MicroRNAs (miRNAs) are a group of tiny RNAs that do not code for proteins. They play a substantial role in controlling gene expression after the process of transcription. miRNAs have a pivotal role in the underlying pathological mechanisms of various neurodegenerative diseases, including PD. The objective of this research initiative is to create a molecular network in order to identify miRNAs that have significant impacts on the evolution of PD, with the intention of utilising them for instant diagnosis as well as prompt prognosis.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"278 ","pages":"Article 110542"},"PeriodicalIF":4.6,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144223132","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":"Prolonged nicotine exposure, via electronic cigarette, selectively increases Bdnf/TrkB transcription, dynorphin peptide levels and OLIG2 in male rat VTA","authors":"Laura Rullo ,&nbsp;Camilla Morosini ,&nbsp;Loredana Maria Losapio ,&nbsp;Fabio Vivarelli ,&nbsp;Moreno Paolini ,&nbsp;Lucy C. Fairclough ,&nbsp;Donatella Canistro ,&nbsp;Patrizia Romualdi ,&nbsp;Sanzio Candeletti","doi":"10.1016/j.neuropharm.2025.110540","DOIUrl":"10.1016/j.neuropharm.2025.110540","url":null,"abstract":"<div><div>Different drugs of abuse affect the Central Nervous System (CNS) neuronal networks and reshape the expression of neuroplasticity-related genes in crucial parts of the mesocorticolimbic reward circuitry, such as the ventral tegmental area (VTA) and the nucleus accumbens (NAc). Recent evidence suggests that neuronal activity and life experience, including repeated drug exposure, can modulate oligodendrogenesis thus altering neuronal myelination. This study aimed to investigate whether the prolonged exposure to nicotine, via electronic cigarettes, affects oligodendrocyte differentiation. Results showed that exposure to nicotine mainstream enhances the expression of OLIG2, a transcription factor essential for oligodendrocyte differentiation, in male rat VTA. This effect was associated with increased mRNA levels of the epigenetic enzyme <em>Kdm6b</em>, which is involved in regulating OLIG2 expression and synaptic plasticity. In the same brain region, nicotine increased <em>Bdnf</em> and <em>TrkB</em> gene expression as well as dynorphin peptide levels, which are positive regulators for oligodendroglial differentiation. Noteworthy, these molecular changes occurred alongside a reduction in neurofilament light levels, suggesting potential axonal remodelling associated with enhanced oligodendrogenesis. No significant changes in investigated parameters were detected in the NAc, thus suggesting that the reported molecular alterations selectively occurred in the VTA. Protein correlation analysis revealed that prolonged nicotine exposure primarily affects neuroplasticity-related protein networks within this area. Overall, these findings suggest that prolonged nicotine exposure, through electronic cigarettes, induces alterations of oligodendrogenesis modulators in the VTA. These molecular changes may impact axonal conduction velocity and reward circuitry connectivity, promoting neuronal adaptations that could be relevant for the development of addictive behaviour.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"278 ","pages":"Article 110540"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216339","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 effects of urolithin a in a mouse model of intracerebral hemorrhage","authors":"Yan Guo ,&nbsp;Xiangyu Zhang ,&nbsp;Jianzhong Deng ,&nbsp;Qiuyang Su ,&nbsp;Yuanyuan Liu ,&nbsp;Gaili Yan ,&nbsp;Sara Xue ,&nbsp;V. Wee Yong ,&nbsp;Mengzhou Xue","doi":"10.1016/j.neuropharm.2025.110538","DOIUrl":"10.1016/j.neuropharm.2025.110538","url":null,"abstract":"<div><div>Intracerebral hemorrhage (ICH) accounts for 10–15 % of all stroke cases and is associated with high mortality and morbidity. Brain injury caused by ICH includes primary and secondary brain injury. Neuroinflammation and apoptosis play important roles in the pathological process of secondary brain injury after ICH. Urolithin A (UroA) is a metabolite derived from ellagic acid and has been confirmed to be anti-inflammatory, anti-oxidant and anti-apoptotic. The aim of this study was to investigate the effects of UroA on neuroinflammation and neuronal apoptosis in a mouse model of ICH induced by collagenase. Compared with ICH mice given vehicle, intraperitoneal injection of UroA (2.5 mg/kg) significantly reduced neurological impairment and brain water content 3 days after ICH. UroA reduced Evans Blue exudation and the loss of zonula occludens-1 and Occludin. Western blot showed that UroA significantly decreased the concentration of matrix metalloproteinases-9 (MMP-9). UroA treatment significantly attenuated the density of activated microglia and infiltrated neutrophils after 3 days of ICH. Finally, UroA inhibited cell death around the hematoma, attenuated ipsilateral brain injury, and improved neurological function in mice with ICH. UroA plays a neuroprotective role in ICH by inhibiting the expression of MMP-9 and reducing neuroinflammation, blood-brain barrier destruction, brain cell death and brain injury.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"278 ","pages":"Article 110538"},"PeriodicalIF":4.6,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192043","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":"Evaluating the neuroprotective effects of the novel Kv2.1 blocker Zj7923 against ischemic stroke in vitro and in vivo","authors":"Tianjiao Yang,&nbsp;Weiping Wang,&nbsp;Zhuo Li,&nbsp;Jie Cai,&nbsp;Nan Feng,&nbsp;Shaofeng Xu,&nbsp;Ling Wang,&nbsp;Xiaoliang Wang","doi":"10.1016/j.neuropharm.2025.110537","DOIUrl":"10.1016/j.neuropharm.2025.110537","url":null,"abstract":"<div><div>The voltage-dependent potassium channel Kv2.1 correlates closely to the regulation of neuronal excitability and cellular apoptosis. Ischemia or oxidative treatment were known to stimulate the surge of Kv2.1-mediated current to activate neuronal apoptosis pathways, while inhibiting excessive Kv2.1 K⁺ current efflux could reduce neuronal apoptosis and exhibit neuroprotective effects. Here, we found a novel Kv2.1 selective blocker Zj7923 and investigated whether it produces neuroprotective function after ischemic stroke animal model. We demonstrate that Zj7923 potently inhibits Kv2.1 current with an IC₅₀ of 0.12 μM. Zj7923 had no obvious effect on the activation process of Kv2.1 channels, but could significantly accelerate the inactivation process of Kv2.1 channels. The mutations at Y380 and K356 in the outer vestibule of Kv2.1 channels weakened the inhibitory effect of Zj7923, and the IC₅₀ value of Zj7923 on the mutation channels increased to 3.66 μM and 3.20 μM, respectively, indicating that the compound may act on the above two positions. Zj7923 could increase the spontaneous firing rate of normal hippocampal pyramidal neurons and ameliorate OGD-induced impairment of neuronal excitability. Kv2.1 channel inhibition by Zj7923 provides protection against DTDP-induced apoptosis and its mechanism might be related to the modulation of the expression of apoptosis-related proteins, such as Bcl-2, Bax and cleaved caspase-3 proteins. <em>In vivo</em> pharmacodynamics evaluation, intravenous administration of Zj7923 in rats following transient middle cerebral artery occlusion significantly reduced infarct volume and improved neurological deficits. Our results indicate that Zj7923 exerts a neuronal protection from cerebral ischemia <em>in vitro</em> and <em>in vivo</em> by inhibiting Kv2.1 current and validate the potential value of developing drugs targeting Kv2.1 for ischemic stroke.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"278 ","pages":"Article 110537"},"PeriodicalIF":4.6,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192042","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":"FGF21 alleviates α-II-spectrin breakdown in a model of oxygen-glucose deprivation and modulates global protein phosphorylation in hippocampal neurons","authors":"Kiersten Gorse ,&nbsp;Kara Snyder ,&nbsp;Travis C. Jackson","doi":"10.1016/j.neuropharm.2025.110529","DOIUrl":"10.1016/j.neuropharm.2025.110529","url":null,"abstract":"<div><div>Fibroblast growth factor 21 (FGF21) is a pleiotropic hormone that promotes hippocampal neuroprotection in animal models of ischemic brain injury, but how it works is unclear. In the first experiment we subjected isolated hippocampal neurons to oxygen-glucose deprivation (OGD) injury to test if FGF21 induced neuroprotection is mediated by its direct effects on neurons. Further, because cold stress regulates FGF21 levels in animals, we also explored if post-insult temperature (37 °C versus 33.5 °C) modified FGF21 induced neuroprotection. Experiment 1 revealed that FGF21 treatment at 37 °C decreased α-II-spectrin breakdown product-145 (SBDP-145) levels but did not affect 24 h cell survival. Intraischemic therapeutic hypothermia (TH) decreased SBDP-145 levels and increased 24 h cell survival. Co-treatment with FGF21+TH augmented the effect of cooling to increase the levels of the cold-shock proteins (CSPs) RNA-binding motif 3 (RBM3) and cold-induced RNA-binding protein (CIRBP), without further effecting survival. In Experiment 2, to obtain additional insights on FGF21 signaling responses in neurons, we measured the global phosphoproteome in hippocampal neurons after a 30 min pulse treatment with FGF21, both in normothermic cells and in cells that were subjected to hypothermia for 48 h. This revealed a reprogramming effect of temperature on FGF21 signaling responses. We also identified myristoylated alanine-rich c-kinase substrate-like protein 1 (MARCKSL1) as a novel FGF21 target. In follow-up studies in the OGD model, FGF21 treatment prevented injury induced decreases in MARCKSL1 protein levels. We conclude that FGF21 has a direct inhibitory effect on α-II-spectrin breakdown and modifies neuronal signaling responses in a temperature dependent manner in hippocampal neurons.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"278 ","pages":"Article 110529"},"PeriodicalIF":4.6,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187432","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 neuroprotective effects of N-acetylcysteine in psychiatric and neurodegenerative disorders: From modulation of glutamatergic transmission to restoration of synaptic plasticity.","authors":"Suwarna Chakraborty, Shankaranarayana Rao, Sunil Jamuna Tripathi","doi":"10.1016/j.neuropharm.2025.110527","DOIUrl":"https://doi.org/10.1016/j.neuropharm.2025.110527","url":null,"abstract":"<p><p>N-acetylcysteine (NAC) is an effective pleiotropic drug with a strong safety profile. It is predominantly used as a mucolytic agent and in the treatment of paracetamol overdose. However, extensive research in the last decade has shown the prominent efficacy of NAC in many neuropsychiatric and neurodegenerative disorders. NAC acts through multiple mechanisms; primarily, it releases cysteine and modulates glutamatergic and monoaminergic transmission. Further, it restores glutathione levels, promotes oxidative balance, reverses decreased synaptic plasticity, reduces neuroinflammation and mitochondrial dysfunction, and provides neurotrophic support. Additionally, it regulates one-carbon metabolism pathways, leading to the production of key metabolites. In this review, we will be discussing in-depth mechanisms of action of NAC and its promising ability to reverse neuropathological changes, particularly cognitive deficits, and associated plasticity changes in various psychiatric and neurodegenerative diseases, including depression, bipolar disorders, schizophrenia, Alzheimer's disease, Huntington's disease, traumatic brain injury, aging. Overall, several preclinical studies and clinical trials have demonstrated the efficacy of NAC in reversing regressive plasticity, cognitive deficits, and associated changes in the brain. NAC remains among the strongest candidates with a high safety profile for managing several types of neurological disorders.</p>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":" ","pages":"110527"},"PeriodicalIF":4.6,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143276","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 novel compound CP-10 suppresses microglia-mediated neuroinflammation and neutrophil chemotaxis and attenuates ischemic brain injury by targeting FPR1","authors":"Meng-qi Dong ,&nbsp;Yan Chen ,&nbsp;Qing Wang ,&nbsp;Hui-qin Li ,&nbsp;Ling-yun Bai ,&nbsp;Xiang Cao ,&nbsp;Yun Xu","doi":"10.1016/j.neuropharm.2025.110528","DOIUrl":"10.1016/j.neuropharm.2025.110528","url":null,"abstract":"<div><div>Ischemic stroke represents a major neurological disorder characterized by significant morbidity, where neuroinflammation plays a central role in exacerbating cerebral injury. Following ischemic events, microglial activation and the subsequent infiltration of peripheral immune cells, particularly neutrophils, contribute to the disruption of the blood-brain barrier and amplify neuronal damage. In the present study, as a part of our ongoing screening experiment to evaluate the anti-inflammatory effects of new compounds, a novel compound, namely N-{2-[(7-chloro-4-oxo-4H-pyrido[1,2-a] pyrimidin-2-yl) methoxy] phenyl}-2,2-dimethylpropanamide (referred to as CP-10 in this study), to test whether it could target microglial activation and neutrophil chemotaxis, both critical contributors to ischemic brain injury. CP-10 exhibited no apparent cytotoxicity to primary microglia or neurons at concentrations up to 30 μM. Transcriptomic analysis revealed that CP-10 modulated a wide range of inflammatory and immune response genes, particularly those associated with neutrophil chemotaxis, such as Cxcl1, Cxcl2, Cxcl3, and Cxcl5. Mechanistically, CP-10 exerted its effects by interacting with formyl peptide receptor 1 (FPR1), a receptor involved in microglial activation and neutrophil recruitment. In vivo, CP-10 significantly reduced infarct volume and neurological deficits in a mouse model of middle cerebral artery occlusion (MCAO), accompanied by reduced neutrophil infiltration and microglial activation in the ischemic penumbra. Furthermore, CP-10 inhibited key inflammatory signaling pathways, including NF-κB and MAPK, downstream of FPR1 activation. These findings position CP-10 as a promising candidate for ischemic stroke therapy, targeting neuroinflammation and immune cell chemotaxis via FPR1 modulation.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"277 ","pages":"Article 110528"},"PeriodicalIF":4.6,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144139424","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":"Dimercaprol attenuates oxidative stress-induced damage of retinal ganglion cells in an in vitro and in vivo model of traumatic optic neuropathy","authors":"Xiangpeng Tan ,&nbsp;Meiting Han ,&nbsp;Mengke Han ,&nbsp;Shuo Ren ,&nbsp;Yue Sun ,&nbsp;Xiaoqing Zeng ,&nbsp;Xin Liu ,&nbsp;Lin Yan ,&nbsp;Abekah Gabriel ,&nbsp;Qingqing Yao ,&nbsp;Dulin Kong ,&nbsp;Xiaohui Wang ,&nbsp;Jianzhang Wu ,&nbsp;Wencan Wu","doi":"10.1016/j.neuropharm.2025.110525","DOIUrl":"10.1016/j.neuropharm.2025.110525","url":null,"abstract":"<div><div>Traumatic optic neuropathy (TON) is a prevalent form of optic neuropathy, which is a significant cause of irreversible blindness. To date, effective therapeutic interventions for TON are lacking, highlighting the urgent need for the development of new therapeutic drugs. In this study, a compound library comprising 480 Food and Drug Administration (FDA)-approved drugs was screened to identify potentially effective therapeutic drugs for TON. We reported that dimercaprol (DMP), an FDA-approved drug, can reduce L-Glutamic acid (Glu) and hydrogen peroxide (H₂O₂)-induced injury in a retinal cell line (R28 cell). Our findings further demonstrated that intracellular reactive oxygen species (ROS) and acrolein, a lipid peroxide, are major contributors to apoptosis-induced cell death <em>in vitro</em>. A series of functional assays revealed that DMP can inhibit apoptosis-induced by Glu via scavenging of intracellular ROS and acrolein in R28 cells and primary cortical neurones. Notably, DMP inhibited retinal ganglion cell complex (GCC) thinning and retinal ganglion cell (RGC) loss resulting from optic nerve crush (ONC) injury <em>in vivo</em>. Moreover, DMP effectively eliminated ONC-induced acrolein in the retina and inhibited RGC apoptosis <em>in vivo</em>. In conclusion, intracellular ROS and acrolein play significant roles in RGC loss in TON, and DMP effectively inhibits RGC apoptosis-induced by the oxidative stress pathway <em>in vitro</em> and <em>in vivo</em>. Therefore, DMP has emerged as a potential new therapeutic drug against TON.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"277 ","pages":"Article 110525"},"PeriodicalIF":4.6,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132479","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":"Low-dose cannabidiol treatment prevents chronic stress-induced phenotypes and is associated with multiple synaptic changes across various brain regions","authors":"Sara Borràs-Pernas ,&nbsp;Anna Sancho-Balsells ,&nbsp;Lisa Patterer ,&nbsp;Maoyu Wang ,&nbsp;Daniel del Toro ,&nbsp;Jordi Alberch ,&nbsp;Daniele Schibano ,&nbsp;Joan Espel ,&nbsp;Maya Heybeck ,&nbsp;Bernhard Scheidel ,&nbsp;Albert Giralt","doi":"10.1016/j.neuropharm.2025.110526","DOIUrl":"10.1016/j.neuropharm.2025.110526","url":null,"abstract":"<div><div>Major Depressive Disorder (MDD) is a heterogeneous and debilitating mood disorder often associated with stress. Although current treatments are available, they remain ineffective for approximately 30 % of affected individuals and are frequently accompanied by undesirable side effects. Cannabidiol (CBD) has emerged as a potential and safe therapeutic option for alleviating depressive symptoms; however, the underlying molecular mechanisms through which this compound exerts its beneficial effects are not yet fully understood. In this study, we demonstrate that a very low dose of CBD (1 mg/kg) can partially reverse some sequelae induced by chronic stress, a well-established mouse model used to simulate depressive-like symptoms. Using mass spectrometry to analyze different brain regions, we observed several improvements following CBD treatment, particularly in the medial prefrontal cortex (mPFC), across multiple neurotransmission systems (including glutamatergic and serotonergic pathways). Microstructural experiments, utilizing double-labeling of F-Actin and VGlut1-positive clusters, revealed a complete restoration of mature synapses in the mPFC of mice treated with CBD. In conclusion, our findings indicate that a very low dose of CBD is effective in counteracting the adverse effects of chronic stress, possibly through the synaptic remodeling of excitatory synapses in the mPFC.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"277 ","pages":"Article 110526"},"PeriodicalIF":4.6,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132480","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}