Tina T Vo, Shandell Pahlen, Anqing Zheng, Sian Yu, Emery Lor, Nicholas D Bowman, Robin P Corley, Naomi P Friedman, Sally J Wadsworth, Chandra A Reynolds
{"title":"From controllers to cognition: the importance of selection factors on video game and gameplay mechanic-derived cognitive differences.","authors":"Tina T Vo, Shandell Pahlen, Anqing Zheng, Sian Yu, Emery Lor, Nicholas D Bowman, Robin P Corley, Naomi P Friedman, Sally J Wadsworth, Chandra A Reynolds","doi":"10.1186/s12993-024-00258-7","DOIUrl":"https://doi.org/10.1186/s12993-024-00258-7","url":null,"abstract":"<p><p>Playing video games, especially games with action-based mechanics, is correlated with better cognitive performance, yet these performance advantages may originate from intrinsic factors such as earlier life cognitive differences. We investigated whether gaming-cognition associations in a sample past young adulthood remain robust after accounting for adolescent cognitive functioning. Using data from the Colorado Adoption/Twin Study of Lifespan behavioral development and cognitive aging (CATSLife; N = 1241, M<sub>age</sub> = 33.3, %, age range = 28-51, Female = 52.9%), we compared cognitive performance of adult recreational gamers (40.6%) to non-gamers (59.4%) and between different types of gamers. Measures included processing speed, spatial reasoning, and working memory cognitive tasks, gaming status, and gameplay type engagement. The majority of gamer participants reported exclusively playing puzzle/strategy/life simulation games (53.0%) or action type games (33.1%); a smaller proportion reported playing both types of games (10.3%). Overall, gamers significantly outperformed non-gamers across most cognitive tasks (Cohen's d = 0.17-0.25), with limited evidence of a differential gameplay mechanic effect across tasks. Selection effects were evident whereby after adolescent IQ adjustment, gamer cognitive effects diminished by over 35% but persisted for spatial performance. Adolescent IQ predicted puzzle/strategy/life simulation preference but not action-type games, suggesting a selection effect. Our study replicates prior gaming findings and reveals that earlier life functioning contributes to adult gaming-cognition associations. Gamer-spatial associations are not fully attributable to intrinsic factors, and playing video games, regardless of a specific gameplay mechanic or genre, may represent a cognitively engaging lifestyle behavior that may benefit cognitive functioning, with implications for preserved cognition.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":"20 1","pages":"35"},"PeriodicalIF":4.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142870819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shruthi S Sharma, Arun Sasidharan, D Yoganarasimha, T R Laxmi
{"title":"Characterization of neuronal oscillations in the prelimbic cortex, nucleus accumbens and CA1 hippocampus during object retrieval task in rats predisposed to early life stress.","authors":"Shruthi S Sharma, Arun Sasidharan, D Yoganarasimha, T R Laxmi","doi":"10.1186/s12993-024-00255-w","DOIUrl":"https://doi.org/10.1186/s12993-024-00255-w","url":null,"abstract":"<p><strong>Background: </strong>Early life stress (ELS) during the stress hypo-responsive period (SHRP) alters the curiosity-like behavior later during adolescence. Previous studies have shown maternal separation (MS) stress-induced heightened curiosity and associated risk-taking behavior in the object retrieval task (ORT). However, the neural correlates of curiosity in adolescent rats predisposed to early life stress remain unexplored. Hence, the present study aimed to investigate the neural oscillatory patterns and network characteristics in the regions implicated in curiosity behavior, such as the Prelimbic cortex (PL), Nucleus Accumbens (NAc), and CA1 of the Hippocampus. The local field potentials data were analysed to understand the neural activity patterns in these areas during the risky zone crossing and object retrieval phase of the ORT in MS rats and compared with the normal control (NC) group.</p><p><strong>Results: </strong>In comparison to NC, MS rats showed a reduction in the theta power at 8-12 Hz, beta power at 12-20 Hz, and gamma power at 20-40 Hz range in the PL during risky zone crossing time. MS rats also showed reduced cross-correlation between PL-CA1 and reduced theta coherence between NAc-CA1 during risky zone crossing. During the object retrieval phase, the MS rats showed reduced peak cross-correlation between PL-CA1 and PL-NAc. Behaviourally, MS rats displayed an increased preference for the curiosity platform and retrieved more hidden objects, thus accounting for a higher curiosity index than controls.</p><p><strong>Conclusion: </strong>In summary, a reduced synchronization between the PL, NAc, and CA1 during the object retrieval task indicates how early MS stress during a critical developmental period impacts the limbic circuit connectivity. This corresponded with enhanced curiosity index in adolescent MS rats, predicting an altered intrinsic motivation and hence a higher susceptibility to substance use disorders during adolescence.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":"20 1","pages":"34"},"PeriodicalIF":4.7,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chih-Zen Chang, Shu-Chuan Wu, Aij-Lie Kwan, Chih-Lung Lin
{"title":"Retraction Note: 4'‑O‑β‑D‑glucosyl‑5‑O‑methylvisamminol, an active ingredient of Saposhnikovia divaricata, attenuates high‑mobility group box 1 and subarachnoid hemorrhage‑induced vasospasm in a rat model.","authors":"Chih-Zen Chang, Shu-Chuan Wu, Aij-Lie Kwan, Chih-Lung Lin","doi":"10.1186/s12993-024-00263-w","DOIUrl":"10.1186/s12993-024-00263-w","url":null,"abstract":"","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":"20 1","pages":"33"},"PeriodicalIF":4.7,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11636009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chih-Lin Lee, Yu-Shan Su, Chi-Yu Chang, Tzu-Yun Kung, Yu-Kai Ma, Pei-Yun Zeng, Ching-Chuan Cheng, Yu-Jen Chang, Yu-Ju Chou, Tsung-Han Kuo
{"title":"Uncovering hidden prosocial behaviors underlying aggression motivation in mice and young children.","authors":"Chih-Lin Lee, Yu-Shan Su, Chi-Yu Chang, Tzu-Yun Kung, Yu-Kai Ma, Pei-Yun Zeng, Ching-Chuan Cheng, Yu-Jen Chang, Yu-Ju Chou, Tsung-Han Kuo","doi":"10.1186/s12993-024-00260-z","DOIUrl":"10.1186/s12993-024-00260-z","url":null,"abstract":"<p><strong>Background: </strong>Animals exhibit a wide range of social behaviors, including positive actions that promote social cohesion and negative behaviors associated with asserting dominance. While these behaviors are often viewed as opposites, they can also exist independently or coexist in complex ways, necessitating further investigation into their interrelationships.</p><p><strong>Results: </strong>To study the interplay between these two types of behaviors, we examined mouse social behaviors using resident-intruder assays and revealed a negative correlation between social aggression and prosocial allogrooming. Suppressing aggressive motivation through various manipulations, including social subordination, olfaction ablation, and inhibition of aggressive neural circuits, led to an increased display of allogrooming behavior. The mouse findings prompted us to further explore the relationship between aggression and prosocial behaviors in preschool children. Similarly, we observed a negative association between aggression and prosocial behaviors, which were potentially influenced by their inhibitory control abilities.</p><p><strong>Conclusions: </strong>Through this cross-species study, we uncovered the inhibitory impact of aggressive neural circuits on mouse allogrooming and established a link between aggression and prosocial behaviors in children. These insights offer valuable implications for understanding and potentially influencing social interactions in both animal and human contexts, with potential applications in preschool education practices.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":"20 1","pages":"32"},"PeriodicalIF":4.7,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11605964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Romi Sagi, Moumita Chakraborty, Milos Bogdanovic, Hila Asraf, Israel Sekler, Ora Kofman, Hagit Cohen, Michal Hershfinkel
{"title":"Loss of the zinc receptor ZnR/GPR39 in mice enhances anxiety-related behavior and motor deficits, and modulates KCC2 expression in the amygdala.","authors":"Romi Sagi, Moumita Chakraborty, Milos Bogdanovic, Hila Asraf, Israel Sekler, Ora Kofman, Hagit Cohen, Michal Hershfinkel","doi":"10.1186/s12993-024-00254-x","DOIUrl":"10.1186/s12993-024-00254-x","url":null,"abstract":"<p><strong>Background: </strong>Mood disorders, particularly depression and anxiety, are associated with zinc dyshomeostasis and aberrant GABAergic signaling. Activation of ZnR/GPR39 by synaptic zinc in the hippocampus triggers phosphorylation of extracellular regulated kinase (ERK1/2), which regulates the K<sup>+</sup>/Cl<sup>-</sup> cotransporter (KCC2) and thereby GABAergic inhibitory neurotransmission and seizure activity. Therefore, we studied whether impaired ZnR/GPR39 signaling is linked to anxiety-related behavior in male or female mice.</p><p><strong>Results: </strong>Using the acoustic startle response, elevated plus maze, and open field test, we found increased anxiety-related behavior in ZnR/GPR39 knockout (KO) mice. Despite a well-established sex difference, where females are typically more prone to anxiety, both male and female ZnR/GPR39 KO mice exhibited increased anxiety-related behavior compared to wildtype (WT) mice. Additionally, ZnR/GPR39 KO mice displayed impaired motor coordination in the pole and rotarod tests but did not show reduced muscle strength, as indicated by a grip test. Finally, we found intrinsic alterations in the expression level of KCC2, a major Cl<sup>-</sup> transporter regulating GABAergic signaling, in the amygdala of naïve ZnR/GPR39 KO mice compared to controls.</p><p><strong>Conclusions: </strong>Our findings indicate that loss of ZnR/GPR39 enhances anxiety-related behavior in both male and female mice. Moreover, ZnR/GPR39 KO mice exhibit impaired motor coordination, which may be associated with increased anxiety. Finally, we demonstrate that loss of ZnR/GPR39 modulates the expression of KCC2 in the amygdala. Thus, we propose that ZnR/GPR39 can serve as a target for regulating GABAergic signaling in anxiety treatment.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":"20 1","pages":"31"},"PeriodicalIF":4.7,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Spectral tuning and after-effects in neural entrainment.","authors":"Maëlan Q Menétrey, David Pascucci","doi":"10.1186/s12993-024-00259-6","DOIUrl":"10.1186/s12993-024-00259-6","url":null,"abstract":"<p><p>Neural entrainment has become a popular technique to non-invasively manipulate brain rhythms via external, periodic stimulation. However, there is still debate regarding its underlying mechanisms and effects on brain activity. Here, we used EEG recordings during a visual entrainment paradigm to assess characteristic changes in the spectral content of EEG signals due to entrainment. Our results demonstrate that entrainment not only increases synchrony between neural oscillations and the entraining stimulus but also elicits previously unreported spectral tuning effects and long-lasting after-effects. These findings offer compelling evidence for the presence of dedicated, flexible, and adaptive mechanisms for neural entrainment, which may have key roles in adjusting the sensitivity and dynamic range of brain oscillators in response to environmental temporal structures.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":"20 1","pages":"29"},"PeriodicalIF":4.7,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cutibacterium Acnes induces Alzheimer's disease-like pathology in brains of wistar rats through structural changes associated with microtubules.","authors":"Morteza Aliashrafi, Mohammad Nasehi, Seyed Davar Siadat, Mohammad-Hossein Mohammadi-Mahdiabadi-Hasani, Hakimeh Zali, Zahra Niknam","doi":"10.1186/s12993-024-00257-8","DOIUrl":"10.1186/s12993-024-00257-8","url":null,"abstract":"<p><strong>Background: </strong>Cutibacterium acnes(C. acnes), a Gram-positive anaerobe and a dominant bacterium species in the sebaceous follicles of the face was detected in the brain of Alzheimer's disease (AD) patients. It has been found that C. acnes activates non-specifically the innate immune system by producing proinflammatory cytokines and can participate in brain inflammation. We hypothesise that C. acnes could influence the brain through the structural alteration in axons and dendrites of neurons.</p><p><strong>Methods: </strong>In this regard, the hippocampus of rats was infected with C. acnes, and memory retention, amyloid-β (Aβ<sub>1-42</sub>) deposition, hyperphosphorylated tau protein (p-Tau) formation, and expression levels of MAP2 and β-tubulin proteins in the hippocampus tissues were investigated.</p><p><strong>Results: </strong>C. acnes-infected rats displayed memory deficits and Aβ<sub>1-42</sub> deposits were detected in their hippocampus tissue up to 7 days post-infection. C. acnes was neurotoxic and exerted detrimental effects on MAP2 and β-tubulin proteins, which are required for normal neuronal function. An elevated level of p-Tau was also identified in infected animals.</p><p><strong>Conclusion: </strong>Based on these results, we propose that C. acnes infection of the brain participates in the initiation of the pathogenesis of sporadic AD through degeneration of axons and dendrites.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":"20 1","pages":"30"},"PeriodicalIF":4.7,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11583404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sonia Burgaz, Elisa Navarro, Santiago Rodríguez-Carreiro, Carmen Navarrete, Martin Garrido-Rodríguez, Isabel Lastres-Becker, Julia Chocarro, José L Lanciego, Eduardo Muñoz, Javier Fernández-Ruiz
{"title":"Investigation in the cannabigerol derivative VCE-003.2 as a disease-modifying agent in a mouse model of experimental synucleinopathy.","authors":"Sonia Burgaz, Elisa Navarro, Santiago Rodríguez-Carreiro, Carmen Navarrete, Martin Garrido-Rodríguez, Isabel Lastres-Becker, Julia Chocarro, José L Lanciego, Eduardo Muñoz, Javier Fernández-Ruiz","doi":"10.1186/s12993-024-00256-9","DOIUrl":"10.1186/s12993-024-00256-9","url":null,"abstract":"<p><strong>Background: </strong>The cannabigerol derivative VCE-003.2, which has activity at the peroxisome proliferator-activated receptor-γ has afforded neuroprotection in experimental models of Parkinson's disease (PD) based on mitochondrial dysfunction (6-hydroxydopamine-lesioned mice) and neuroinflammation (LPS-lesioned mice). Now, we aim to explore VCE-003.2 neuroprotective properties in a PD model that also involves protein dysregulation, other key event in PD pathogenesis.</p><p><strong>Methods: </strong>To this end, an adeno-associated viral vector serotype 9 coding for a mutated form of the α-synuclein gene (AAV9-SynA53T) was unilaterally delivered in the substantia nigra pars compacta (SNpc) of mice. This model leads to motor impairment and progressive loss of tyrosine hydroxylase-labelled neurons in the SNpc.</p><p><strong>Results: </strong>Oral administration of VCE-003.2 at 20 mg/kg for 14 days improved the performance of mice injected with AAV9-SynA53T in various motor tests, correlating with the preservation of tyrosine hydroxylase-labelled neurons in the SNpc. VCE-003.2 also reduced reactive microgliosis and astrogliosis in the SNpc. Furthermore, we conducted a transcriptomic analysis in the striatum of mice injected with AAV9-SynA53T and treated with either VCE-003.2 or vehicle, as well as control animals. This analysis aimed to identify gene families specifically altered by the pathology and/or VCE-003.2 treatment. Our data revealed pathology-induced changes in genes related to mitochondrial function, lysosomal cell pathways, immune responses, and lipid metabolism. In contrast, VCE-003.2 treatment predominantly affected the immune response through interferon signaling.</p><p><strong>Conclusion: </strong>Our study broadens the neuroprotective potential of VCE-003.2, previously described against mitochondrial dysfunction, oxidative stress, glial reactivity and neuroinflammation in PD. We now demonstrate its efficacy against another key pathogenic event in PD as α-synuclein dysregulation. Furthermore, our investigation sheds light on the molecular mechanisms underlying VCE-003.2 revealing its role in regulating interferon signaling. These findings, together with a favorable ADMET profile, enhance the preclinical interest of VCE-003.2 towards its future clinical development in PD.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":"20 1","pages":"28"},"PeriodicalIF":4.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cofilin linked to GluN2B subunits of NMDA receptors is required for behavioral sensitization by changing the dendritic spines of neurons in the caudate and putamen after repeated nicotine exposure.","authors":"Sunghyun Kim, Sumin Sohn, Eun Sang Choe","doi":"10.1186/s12993-024-00253-y","DOIUrl":"https://doi.org/10.1186/s12993-024-00253-y","url":null,"abstract":"<p><strong>Background: </strong>Nicotine dependence is associated with glutamatergic neurotransmission in the caudate and putamen (CPu) of the forebrain which includes alterations in the structure of dendritic spines at glutamate synapses. These changes after nicotine exposure can lead to the development of habitual behaviors such as smoking. The present study investigated the hypothesis that cofilin, an actin-binding protein that is linked to the GluN2B subunits of N-methyl-D-aspartate (NMDA) receptors regulates the morphology of dendritic spines in the neurons of the CPu after repeated exposure to nicotine.</p><p><strong>Results: </strong>Adult male rats received subcutaneous injections of nicotine (0.3 mg/kg/day) or vehicle for seven consecutive days. DiI staining was conducted to observe changes in dendritic spine morphology. Repeated subcutaneous injections of nicotine decreased the phosphorylation of cofilin while increasing the formation of thin spines and filopodia in the dendrites of medium spiny neurons (MSN) in the CPu of rats. Bilateral intra-CPu infusion of the cofilin inhibitor, cytochalasin D (12.5 µg/µL/side), restored the thin spines and filopodia from mushroom types after repeated exposure to nicotine. Similar results were obtained from the bilateral intra-CPu infusion of the selective GluN2B subunit antagonist, Ro 25-6981 (4 µM/µL/side). Bilateral intra-CPu infusion of cytochalasin D that interferes with the actin-cofilin interaction attenuated the repeated nicotine-induced increase in locomotor sensitization in rats.</p><p><strong>Conclusions: </strong>These findings suggest that active cofilin alters the structure of spine heads from mushroom to thin spine/filopodia by potentiating actin turnover, contributing to behavioral sensitization after nicotine exposure.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":"20 1","pages":"27"},"PeriodicalIF":4.7,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11479554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142456967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eman A E Farrag, Mona H Askar, Zienab Abdallah, Safinaz M Mahmoud, Eman A Abdulhai, Eman Abdelrazik, Eman Mohamad El Nashar, Faten Mohammed Alasiri, Asma Nasser Saeed Alqahtani, Mamdouh Eldesoqui, Ali M Eldib, Alshimaa Magdy
{"title":"Comparative effect of atorvastatin and risperidone on modulation of TLR4/NF-κB/NOX-2 in a rat model of valproic acid-induced autism.","authors":"Eman A E Farrag, Mona H Askar, Zienab Abdallah, Safinaz M Mahmoud, Eman A Abdulhai, Eman Abdelrazik, Eman Mohamad El Nashar, Faten Mohammed Alasiri, Asma Nasser Saeed Alqahtani, Mamdouh Eldesoqui, Ali M Eldib, Alshimaa Magdy","doi":"10.1186/s12993-024-00250-1","DOIUrl":"10.1186/s12993-024-00250-1","url":null,"abstract":"<p><strong>Background: </strong>Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that is significantly increasing, resulting in severe distress. The approved treatment for ASD only partially improves the sympoms, but it does not entirely reverse the symptoms. Developing novel disease-modifying drugs is essential for the continuous improvement of ASD. Because of its pleiotropic effect, atorvastatin has been garnered attention for treating neuronal degeneration. The present study aimed to investigate the therapeutic effects of atorvastatin in autism and compare it with an approved autism drug (risperidone) through the impact of these drugs on TLR4/NF-κB/NOX-2 and the apoptotic pathway in a valproic acid (VPA) induced rat model of autism.</p><p><strong>Methods: </strong>On gestational day 12.5, pregnant rats received a single IP injection of VPA (500 mg/kg), for VPA induced autism, risperidone and atorvastatin groups, or saline for control normal group. At postnatal day 21, male offsprings were randomly divided into four groups (n = 6): control, VPA induced autism, risperidone, and atorvastatin. Risperidone and atorvastatin were administered from postnatal day 21 to day 51. The study evaluated autism-like behaviors using the three-chamber test, the dark light test, and the open field test at the end of the study. Biochemical analysis of TLR4, NF-κB, NOX-2, and ROS using ELISA, RT-PCR, WB, histological examination with hematoxylin and eosin and immunohistochemical study of CAS-3 were performed.</p><p><strong>Results: </strong>Male offspring of prenatal VPA-exposed female rats exhibited significant autism-like behaviors and elevated TLR4, NF-κB, NOX-2, ROS, and caspase-3 expression. Histological analysis revealed structural alterations. Both risperidone and atorvastatin effectively mitigated the behavioral, biochemical, and structural changes associated with VPA-induced rat model of autism. Notably, atorvastatin group showed a more significant improvement than risperidone group.</p><p><strong>Conclusions: </strong>The research results unequivocally demonstrated that atorvastatin can modulate VPA-induced autism by suppressing inflammation, oxidative stress, and apoptosis through TLR4/NF-κB/NOX-2 signaling pathway. Atorvastatin could be a potential treatment for ASD.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":"20 1","pages":"26"},"PeriodicalIF":4.7,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142340239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}