Journal of Neuroscience Research最新文献

{"title":"Modulation of Hypothalamic Dopamine Neuron Activity by Interaction Between Caloric State and Amphetamine in Zebrafish Larvae.","authors":"Pushkar Bansal, Mitchell F Roitman, Erica E Jung","doi":"10.1002/jnr.25396","DOIUrl":"https://doi.org/10.1002/jnr.25396","url":null,"abstract":"<p><p>Dopamine (DA) signaling is evoked by both food and drugs that humans come to abuse. Moreover, physiological state (e.g., hunger versus satiety) can modulate the response. However, there is great heterogeneity among DA neurons. Limited studies have been performed that could resolve the interaction between physiological state and drug responsivity across groups of DA neurons. Here, we measured the activity of neurons in transgenic Tg (th2:GCaMP7s) zebrafish larva that expresses a calcium indicator (GCaMP7s) in A11 (posterior tuberculum) and a part of A14 (caudal hypothalamus and intermediate hypothalamus) DA populations located in the hypothalamus of the larval zebrafish. Fish were recorded in one of two physiological states: ad-libitum fed (AL) and food deprived (FD) and before and after acute exposure to different doses of the stimulant drug amphetamine (0, 0.7, and 1.5 μM). We quantified fluorescence change, activity duration, peak rise/fall time, and latency in the calcium spikes of the DA neurons. Our results show that baseline DA neuron activity amplitude, spike duration, and correlation between inter- and intra-DA neurons were higher in the FD than in the AL state. Dose-dependent AMPH treatment further increased the intensity of these parameters in the neuron spikes but only in the FD state. The DA activity correlation relatively increased in AL state post-AMPH treatment. Given that hunger increases drug reactivity and the probability of relapse to drug seeking, the results support populations of DA neurons as potential critical mediators of the interaction between physiological state and drug reinforcement.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypothalamus Connectivity in Adolescent Myalgic Encephalomyelitis/Chronic Fatigue Syndrome","authors":"Hollie Byrne,&nbsp;Sarah J. Knight,&nbsp;Elisha K. Josev,&nbsp;Adam Scheinberg,&nbsp;Richard Beare,&nbsp;Joseph Y. M. Yang,&nbsp;Stuart Oldham,&nbsp;Katherine Rowe,&nbsp;Marc L. Seal","doi":"10.1002/jnr.25392","DOIUrl":"10.1002/jnr.25392","url":null,"abstract":"<p>Adolescent Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disabling illness of unknown etiology. Increasing evidence suggests hypothalamic involvement in ME/CFS pathophysiology, which has rarely been explored using magnetic resonance imaging (MRI) in the condition. This work aimed to use MRI to examine hypothalamus connectivity in adolescents with ME/CFS and explore how this relates to fatigue severity and illness duration. 25 adolescents with ME/CFS and 23 healthy controls completed a neuroimaging protocol consisting of structural and multishell diffusion-weighted imaging sequences, in addition to the PedsQL Multidimensional Fatigue Scale to assess fatigue severity. Information about illness duration was acquired at diagnosis. Preprocessing and streamlines tractography was performed using <i>QSIPrep</i> combined with a custom parcellation scheme to create structural networks. The number (degree) and weight (strength) of connections between lateralized hypothalamus regions and cortical and subcortical nodes were extracted, and relationships between connectivity measures, fatigue severity, and illness duration were performed using Bayesian regression models. We observed weak-to-moderate evidence of increased degree, but not strength, of connections from the bilateral anterior-inferior (left: <i>pd</i> [%] = 99.18, median [95% CI] = −22.68[−40.96 to 4.45]; right: <i>pd</i> [%] = 99.86, median [95% CI] = −23.35[−38.47 to 8.20]), left anterior-superior (<i>pd</i> [%] = 99.33, median [95% CI] = −18.83[−33.45 to 4.07]) and total left hypothalamus (<i>pd</i> [%] = 99.44, median [95% CI] = −47.18[−83.74 to 11.03]) in the ME/CFS group compared with controls. Conversely, bilateral posterior hypothalamus degree decreased with increasing ME/CFS illness duration (left: <i>pd</i> [%] = 98.13, median [95% CI]: −0.47[−0.89 to 0.03]; right: <i>pd</i> [%] = 98.50, median [95% CI]:-0.43[−0.82 to 0.05]). Finally, a weak relationship between right intermediate hypothalamus connectivity strength and fatigue severity was identified in the ME/CFS group (<i>pd</i> [%] = 99.35, median [95% CI] = −0.28[−0.51 to 0.06]), which was absent in controls. These findings suggest changes in hypothalamus connectivity may occur in adolescents with ME/CFS, warranting further investigation.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jnr.25392","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Parvalbumin Interneurons in Autism Spectrum Disorder","authors":"Yiwei Yao,&nbsp;Qian Li","doi":"10.1002/jnr.25391","DOIUrl":"https://doi.org/10.1002/jnr.25391","url":null,"abstract":"<div>\u0000 \u0000 <p>As an important subtype of GABAergic interneurons, parvalbumin (PV) interneurons play a critical role in regulating cortical circuits and neural networks. Abnormalities in the development or function of PV interneurons have been linked to autism spectrum disorder (ASD), a neurodevelopmental disorder characterized by social and language deficits. In this review, we focus on the abnormalities of PV interneurons in ASD, including quantity and function and discuss the underlying mechanisms of impairments in PV interneurons in the pathology of ASD. Finally, we propose potential therapeutic approaches targeting PV interneurons, such as transplanting MGE progenitor cells and utilizing optogenetic stimulation in the treatment of ASD.</p>\u0000 </div>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ascending Vagal Sensory and Central Noradrenergic Pathways Modulate Retrieval of Passive Avoidance Memory in Male Rats","authors":"Caitlyn M. Edwards,&nbsp;Inge Estefania Guerrero,&nbsp;Danielle Thompson,&nbsp;Tyla Dolezel,&nbsp;Linda Rinaman","doi":"10.1002/jnr.25390","DOIUrl":"10.1002/jnr.25390","url":null,"abstract":"<div>\u0000 \u0000 <p>Visceral feedback from the body is often subconscious, but plays an important role in guiding motivated behaviors. Vagal sensory neurons relay “gut feelings” to noradrenergic (NA) neurons in the caudal nucleus of the solitary tract (cNTS), which in turn project to the anterior ventrolateral bed nucleus of the stria terminalis (vlBNST) and other hypothalamic-limbic forebrain regions. Prior work supports a role for these circuits in modulating memory consolidation and extinction, but a potential role in retrieval of conditioned avoidance remains untested. To examine this, adult male rats underwent passive avoidance conditioning. We then lesioned gut-sensing vagal afferents by injecting cholecystokinin-conjugated saporin toxin (CSAP) into the vagal nodose ganglia (Experiment 1), or lesioned NA inputs to the vlBNST by injecting saporin toxin conjugated to an antibody against dopamine-beta hydroxylase (DSAP) into the vlBNST (Experiment 2). When avoidance behavior was later assessed, rats with vagal CSAP lesions or NA DSAP lesions displayed significantly increased conditioned passive avoidance. These new findings support the view that gut vagal afferents and the cNTS^NA-to-vlBNST circuit play a role in modulating the expression/retrieval of learned passive avoidance. Overall, our data suggest a dynamic modulatory role of vagal sensory feedback to the limbic forebrain in integrating interoceptive signals with contextual cues that elicit conditioned avoidance behavior.</p>\u0000 </div>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of Nocifensive Behavior in NaV1.7–, NaV1.8–, and NaV1.9–Channelrhodopsin-2 Mice by Selective Optogenetic Activation of Targeted Sodium Channel Subtype-Expressing Afferents","authors":"Toyoaki Maruta,&nbsp;Satoshi Kouroki,&nbsp;Mio Kurogi,&nbsp;Kotaro Hidaka,&nbsp;Tomohiro Koshida,&nbsp;Ayako Miura,&nbsp;Hikaru Nakagawa,&nbsp;Toshihiko Yanagita,&nbsp;Ryu Takeya,&nbsp;Isao Tsuneyoshi","doi":"10.1002/jnr.25386","DOIUrl":"10.1002/jnr.25386","url":null,"abstract":"<p>Voltage-gated sodium channels, including Na_V1.7, Na_V1.8, and Na_V1.9, play important roles in pain transmission and chronic pain development. However, the specific mechanisms of their action remain unclear, highlighting the need for in vivo stimulation studies of these channels. Optogenetics, a novel technique for targeting the activation or inhibition of specific neural circuits using light, offers a promising solution. In our previous study, we used optogenetics to selectively excite Na_V1.7-expressing neurons in the dorsal root ganglion of mice to induce nocifensive behavior. Here, we further characterize the impact of nocifensive behavior by activation of Na_V1.7, Na_V1.8, or Na_V1.9-expressing neurons. Using CRISPR/Cas9-mediated homologous recombination, Na_V1.7–iCre, Na_V1.8–iCre, or Na_V1.9–iCre mice expressing iCre recombinase under the control of the endogenous Na_V1.7, Na_V1.8, or Na_V1.9 gene promoter were produced. These mice were then bred with channelrhodopsin-2 (ChR2) Cre–reporter Ai32 mice to obtain Na_V1.7–ChR2, Na_V1.8–ChR2, or Na_V1.9–ChR2 mice. Blue light exposure triggered paw withdrawal in all mice, with the strongest response in Na_V1.8–ChR2 mice. These light sensitivity differences observed across Na_V1.x–ChR2 mice may be dependent on ChR2 expression or reflect the inherent disparities in their pain transmission roles. In conclusion, we have generated noninvasive pain models, with optically activated peripheral nociceptors. We believe that studies using optogenetics will further elucidate the role of sodium channel subtypes in pain transmission.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jnr.25386","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thalamocortical Dysconnectivity in Treatment-Resistant Depression","authors":"Pei-Chi Tu,&nbsp;Wei-Chen Lin,&nbsp;Wan-Chen Chang,&nbsp;Tung-Ping Su,&nbsp;Cheng-Ta Li,&nbsp;Ya-Mei Bai,&nbsp;Shih-Jen Tsai,&nbsp;Mu-Hong Chen","doi":"10.1002/jnr.25388","DOIUrl":"10.1002/jnr.25388","url":null,"abstract":"<p>Thalamocortical connectivity is associated with cognitive and affective processing. The role of thalamocortical connectivity in the pathomechanism of treatment-resistant depression (TRD) remains unclear. This study included 48 patients with TRD and 48 healthy individuals. We investigated thalamocortical connectivity by performing resting-state functional MRI with the bilateral thalamus as the seed. In addition, patients with TRD were evaluated using the Montgomery–Åsberg Depression Rating Scale (MADRS). Compared with the healthy individuals, the patients with TRD exhibited increased functional connectivity (FC) of the thalamus with the insula and superior temporal cortex and reduced the FC of the thalamus with the anterior paracingulate cortex and cerebellum crus II. Our study may support the crucial role of thalamocortical dysconnectivity in the TRD pathomechanism. However, the small sample size may limit the statistical power. A future study with a large sample size of patients with TRD would be required to validate our findings.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jnr.25388","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Comparative Effects Between Long-Term and Short-Term Treatment of Finasteride on Anxiety-Like and Depression-Like Behaviors in Early Senescent Male Rats","authors":"Hiranya Pintana,&nbsp;Nattayaporn Apaijai,&nbsp;Titikorn Chunchai,&nbsp;Chanisa Thonusin,&nbsp;Thiraphat Saengmearnuparp,&nbsp;Aphisek Kongkaew,&nbsp;Nipon Chattipakorn,&nbsp;Siriporn C. Chattipakorn","doi":"10.1002/jnr.25389","DOIUrl":"10.1002/jnr.25389","url":null,"abstract":"<div>\u0000 \u0000 <p>This study aims to compare the efficacy of 5-alpha-reductase inhibitors (5ARIs) on anxiety and depression between long-term and short-term treatment followed by withdrawal in <span>d</span>-galactose (Dgal)–induced senescent male rats. Thirty-two, 8-week-old, male Wistar rats were divided into two groups: control rats and Dgal-treated rats (150 mg/kg/day; subcutaneously) for 18 weeks. At week 13, Dgal-treated rats were subdivided into three subgroups: (1) vehicle (DgV), (2) long-term treatment with 5ARIs, Finasteride 5 mg/kg/day, per oral for 6 weeks (DgF), (3) short-term treatment with 5ARIs, Finasteride 5 mg/kg/day, per oral for 2 weeks followed by a 4-week withdrawal period (DgW). Anxiety and depression were assessed using the elevated-plus maze (EPM) and splash test (ST). Blood was collected for biochemical analysis. After euthanasia, the brains were removed to examine brain inflammation, oxidative stress, neuroactive steroids, brain metabolites, and brain senescent markers. We found that DgV rats exhibited metabolic disturbance with a reduced preference index of the EPM, and grooming duration in ST. Increased brain neurotoxic metabolites, along with increased brain inflammation/oxidative stress, and reduced microglia complexity were observed in the DgV rats. Both therapeutic approaches improved metabolic parameters and preference index in the open arm of EPM in Dgal-treated rats, while grooming duration and microglia complexity were increased only in DgF rats. Our results indicate that Fin reduces depression-like and anxiety-like behaviors by reducing brain inflammation, oxidative stress, and brain senescent. In conclusion, long-term treatment with 5ARIs is more effective in alleviating depression than short-term treatment followed by withdrawal in Dgal-induced early senescent male rats.</p>\u0000 </div>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of the mPFC-NAc Pathway Reduces Motor Impulsivity but Does Not Affect Risk-Related Decision-Making in Innately High-Impulsive Male Rats","authors":"Chloé Arrondeau,&nbsp;Ginna Urueña-Méndez,&nbsp;Florian Marchessaux,&nbsp;Raphaël Goutaudier,&nbsp;Nathalie Ginovart","doi":"10.1002/jnr.25387","DOIUrl":"10.1002/jnr.25387","url":null,"abstract":"<p>Attention-deficit/hyperactivity disorder (ADHD) and substance use disorders (SUD) are characterized by exacerbated motor and risk-related impulsivities, which are associated with decreased cortical activity. In rodents, the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) have been separately implicated in impulsive behaviors, but studies on the specific role of the mPFC-NAc pathway in these behaviors are limited. Here, we investigated whether heightened impulsive behaviors are associated with reduced mPFC activity in rodents and determined the involvement of the mPFC-NAc pathway in motor and risk-related impulsivities. We used the Roman High- (RHA) and Low-Avoidance (RLA) rat lines, which display divergent phenotypes in impulsivity. To investigate alterations in cortical activity in relation to impulsivity, regional brain glucose metabolism was measured using positron emission tomography and [¹⁸F]-fluorodeoxyglucose ([¹⁸F]FDG). Using chemogenetics, the activity of the mPFC-NAc pathway was either selectively activated in high-impulsive RHA rats or inhibited in low-impulsive RLA rats, and the effects of these manipulations on motor and risk-related impulsivity were concurrently assessed using the rat gambling task. We showed that basal [¹⁸F]FDG uptake was lower in the mPFC and NAc of RHA compared to RLA rats. Activation of the mPFC-NAc pathway in RHA rats reduced motor impulsivity, without affecting risk-related decision-making. Conversely, inhibition of the mPFC-NAc pathway had no effect in RLA rats. Our results suggest that the mPFC-NAc pathway controls motor impulsivity, but has limited involvement in risk-related decision-making in our current model. Our findings suggest that reducing fronto-striatal activity may help attenuate motor impulsivity in patients with impulse control dysregulation.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jnr.25387","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pentylenetetrazole-Induced Seizures Cause Short-Term Changes in the Phenotype of Microglial and Astroglial Cells in the Hippocampus and Temporal Cortex of Young Male Wistar Rats","authors":"Maria V. Zakharova,&nbsp;Anna A. Kovalenko,&nbsp;Olga E. Zubareva,&nbsp;Alexander P. Schwarz,&nbsp;Tatiana Y. Postnikova,&nbsp;Alina M. Trofimova,&nbsp;Aleksey V. Zaitsev","doi":"10.1002/jnr.25385","DOIUrl":"https://doi.org/10.1002/jnr.25385","url":null,"abstract":"<div>\u0000 \u0000 <p>Astrocytes and microglia can adopt two distinct phenotypes in various pathological processes: neurotoxic A1/M1 and neuroprotective A2/M2. Recent evidence suggests that these cells play a significant role in epileptogenesis. The objective of this study was to characterize the phenotype of astrocytes and microglial cells in the hippocampus and temporal cortex of young male Wistar rats at 3 h, 1, 3, and 7 days after pentylenetetrazole-induced seizures. RT-qPCR was employed to examine the expression of glial genes (<i>Gfap</i>, <i>Aif1</i>, <i>Slc1a1</i>, <i>Slc1a2</i>, <i>Slc1a3</i>, <i>Itpr2</i>, <i>Gdnf</i>, <i>Bdnf</i>, <i>Fgf2</i>, <i>Tgfb</i>, <i>Il1b</i>, <i>Tnf</i>, <i>Il1rn</i>, <i>Lcn2</i>, <i>S100a10</i>, <i>Nlrp3</i>, <i>Arg1</i>). The most notable alterations in the expression of glial genes were observed on the first day following seizures in the temporal cortex. An increase in the expression of the <i>Gfap</i>, <i>Slc1a2</i>, <i>Slc1a1</i>, <i>Il1b</i>, <i>Tnfa</i>, <i>Bdnf</i>, and <i>Fgf2</i> genes, and the A2 astrocyte condition marker <i>S100a10</i>, was observed. An increase in the expression of the <i>Gfap</i> and <i>Slc1a2</i> genes was observed in the hippocampus on the first day after seizures. However, in contrast to the changes observed in the cortex, the changes in the hippocampus were opposite for the <i>Il1rn</i>, <i>Bdnf</i>, <i>Tgfb</i>, and <i>Arg1</i> genes. Nevertheless, the alterations in GFAP and EAAT2 protein levels were not corroborated by Western blot analysis. Conversely, a more comprehensive immunohistochemical analysis confirmed an augmentation in the number of GFAP-positive cells in the hippocampus 1 day after seizures. Based on the presented evidence, we can conclude that a single convulsive seizure episode in 3-week-old rats results in transient astroglial activation and polarization to a neuroprotective phenotype (A2).</p>\u0000 </div>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142276555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cannabidiol Modulation of Nicotine-Induced Toxicity: Assessing Effects on Behavior, Brain-Derived Neurotrophic Factor, and Oxidative Stress in C57BL/6 Male Mice","authors":"Konstantinos Mesiakaris,&nbsp;Korina Atsopardi,&nbsp;George Lagoumintzis,&nbsp;Marigoula Margarity,&nbsp;Konstantinos Poulas","doi":"10.1002/jnr.25384","DOIUrl":"https://doi.org/10.1002/jnr.25384","url":null,"abstract":"<p>High doses of nicotine administered to rodents serve as a model for studying anxiety and test compounds' potential anxiolytic effects. At these doses, anxiety in rodents is accompanied by disruption of brain-derived neurotrophic factor (BDNF). The endocannabinoids and nicotine modulate several central nervous system processes via their specific receptors, impacting locomotion, anxiety, memory, nociception, and reward. Cannabidiol (CBD), an active ingredient of <i>Cannabis sativa</i> L., is devoid of psychoactive actions and has gained attention for its anxiolytic, antioxidant, and anti-inflammatory properties, among others. This work aims to examine the potential anxiety-reducing properties of CBD in a well-established experimental mouse model of anxiety-like behavior induced by high doses of nicotine on male C57BL/6 mice. In this context, the open-field behavioral test was specially conducted to assess CBD's effects on anxiety-like behavior and locomotion. Brain neuronal plasticity, modulated by BDNF, along with a diverse array of blood's metabolic markers, was examined as a means of evaluating systemic toxicity under various treatments. Finally, oxidative stress was evaluated through the measurement of glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA), while pro-inflammatory cytokine assessments were conducted to evaluate redox status and immune system function. Our research suggests that CBD shows potential in reducing anxiety-like behaviors induced by high doses of nicotine, by mitigating changes in BDNF protein levels in cerebral hemispheres and cerebellum. At the same time, CBD targets specific liver enzymes, maintains tissue's systemic toxicity (i.e., renal, kidney, and pancreatic), balances redox status (SOD, GSH, and MDA), and regulates the secretion of pro-inflammatory cytokines (TNF-alpha and IL-6).</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jnr.25384","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142275092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}