Emerson de Oliveira Ferreira, Jéssica Maria Pessoa Gomes, Kelly Rose Tavares Neves, Francisco Arnaldo Viana Lima, Glauce Socorro de Barros Viana, Geanne Matos de Andrade
{"title":"母体用阿立哌唑治疗可防止幼年雄性小鼠丙戊酸诱导的自闭症样表型的发展。","authors":"Emerson de Oliveira Ferreira, Jéssica Maria Pessoa Gomes, Kelly Rose Tavares Neves, Francisco Arnaldo Viana Lima, Glauce Socorro de Barros Viana, Geanne Matos de Andrade","doi":"10.1097/FBP.0000000000000718","DOIUrl":null,"url":null,"abstract":"<p><p>Autism spectrum disorder (ASD) describes a heterogeneous group of neurodevelopmental conditions characterized by deficits in social communication and repetitive behaviors. Aripiprazole (APZ) is an atypical antipsychotic that can safeguard mice against autism-like behavior induced by valproic acid (VPA). In the present study, we examined the effects of maternal treatment with APZ (10 mg/kg) in juvenile mice prenatally exposed to VPA on neurodevelopmental behaviors, social interactions, communication, and working memory, as well as synaptophysin (SYP), synaptosomal-associated protein, 25 kDa (SNAP-25) and microtubule-associated protein 2 (MAP-2) expression in the medial prefrontal cortex (mPFC) and cell viability in the hippocampus. In addition, to evaluate possible APZ interference with the anticonvulsant properties of VPA on pentylenetetrazole (PTZ)-induced seizures were evaluated. Maternal treatment with APZ significantly prevented body weight loss, self-righting, eye-opening, social interactions, social communication, and working memory deficits in mice prenatally exposed to VPA. Additionally, the decrease in the SYP, SNAP-25, and MAP-2 expressions in the mPFC and cell death in the hippocampus was prevented by APZ. Furthermore, APZ (10 mg/kg) did not interfere with the anticonvulsant effect of VPA (15 mg/kg) in animals with PTZ-induced seizures. These findings indicate that maternal treatment with APZ in pregnant mice exposed to VPA protects animals against the ASD-like behavioral phenotype, and this effect may be related, at least in part, to synaptic plasticity and neuronal protection in the PFC and hippocampus. APZ may serve as an effective pharmacological therapeutic target against autistic behaviors in the VPA animal model of ASD, which should be further investigated to verify its clinical relevance.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":null,"pages":null},"PeriodicalIF":1.6000,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"Maternal treatment with aripiprazole prevents the development of a valproic acid-induced autism-like phenotype in juvenile male mice.\",\"authors\":\"Emerson de Oliveira Ferreira, Jéssica Maria Pessoa Gomes, Kelly Rose Tavares Neves, Francisco Arnaldo Viana Lima, Glauce Socorro de Barros Viana, Geanne Matos de Andrade\",\"doi\":\"10.1097/FBP.0000000000000718\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Autism spectrum disorder (ASD) describes a heterogeneous group of neurodevelopmental conditions characterized by deficits in social communication and repetitive behaviors. Aripiprazole (APZ) is an atypical antipsychotic that can safeguard mice against autism-like behavior induced by valproic acid (VPA). In the present study, we examined the effects of maternal treatment with APZ (10 mg/kg) in juvenile mice prenatally exposed to VPA on neurodevelopmental behaviors, social interactions, communication, and working memory, as well as synaptophysin (SYP), synaptosomal-associated protein, 25 kDa (SNAP-25) and microtubule-associated protein 2 (MAP-2) expression in the medial prefrontal cortex (mPFC) and cell viability in the hippocampus. In addition, to evaluate possible APZ interference with the anticonvulsant properties of VPA on pentylenetetrazole (PTZ)-induced seizures were evaluated. Maternal treatment with APZ significantly prevented body weight loss, self-righting, eye-opening, social interactions, social communication, and working memory deficits in mice prenatally exposed to VPA. Additionally, the decrease in the SYP, SNAP-25, and MAP-2 expressions in the mPFC and cell death in the hippocampus was prevented by APZ. Furthermore, APZ (10 mg/kg) did not interfere with the anticonvulsant effect of VPA (15 mg/kg) in animals with PTZ-induced seizures. These findings indicate that maternal treatment with APZ in pregnant mice exposed to VPA protects animals against the ASD-like behavioral phenotype, and this effect may be related, at least in part, to synaptic plasticity and neuronal protection in the PFC and hippocampus. APZ may serve as an effective pharmacological therapeutic target against autistic behaviors in the VPA animal model of ASD, which should be further investigated to verify its clinical relevance.</p>\",\"PeriodicalId\":8832,\"journal\":{\"name\":\"Behavioural Pharmacology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.6000,\"publicationDate\":\"2023-04-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Behavioural Pharmacology\",\"FirstCategoryId\":\"102\",\"ListUrlMain\":\"https://doi.org/10.1097/FBP.0000000000000718\",\"RegionNum\":4,\"RegionCategory\":\"心理学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BEHAVIORAL SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Behavioural Pharmacology","FirstCategoryId":"102","ListUrlMain":"https://doi.org/10.1097/FBP.0000000000000718","RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BEHAVIORAL SCIENCES","Score":null,"Total":0}
Maternal treatment with aripiprazole prevents the development of a valproic acid-induced autism-like phenotype in juvenile male mice.
Autism spectrum disorder (ASD) describes a heterogeneous group of neurodevelopmental conditions characterized by deficits in social communication and repetitive behaviors. Aripiprazole (APZ) is an atypical antipsychotic that can safeguard mice against autism-like behavior induced by valproic acid (VPA). In the present study, we examined the effects of maternal treatment with APZ (10 mg/kg) in juvenile mice prenatally exposed to VPA on neurodevelopmental behaviors, social interactions, communication, and working memory, as well as synaptophysin (SYP), synaptosomal-associated protein, 25 kDa (SNAP-25) and microtubule-associated protein 2 (MAP-2) expression in the medial prefrontal cortex (mPFC) and cell viability in the hippocampus. In addition, to evaluate possible APZ interference with the anticonvulsant properties of VPA on pentylenetetrazole (PTZ)-induced seizures were evaluated. Maternal treatment with APZ significantly prevented body weight loss, self-righting, eye-opening, social interactions, social communication, and working memory deficits in mice prenatally exposed to VPA. Additionally, the decrease in the SYP, SNAP-25, and MAP-2 expressions in the mPFC and cell death in the hippocampus was prevented by APZ. Furthermore, APZ (10 mg/kg) did not interfere with the anticonvulsant effect of VPA (15 mg/kg) in animals with PTZ-induced seizures. These findings indicate that maternal treatment with APZ in pregnant mice exposed to VPA protects animals against the ASD-like behavioral phenotype, and this effect may be related, at least in part, to synaptic plasticity and neuronal protection in the PFC and hippocampus. APZ may serve as an effective pharmacological therapeutic target against autistic behaviors in the VPA animal model of ASD, which should be further investigated to verify its clinical relevance.
期刊介绍:
Behavioural Pharmacology accepts original full and short research reports in diverse areas ranging from ethopharmacology to the pharmacology of schedule-controlled operant behaviour, provided that their primary focus is behavioural. Suitable topics include drug, chemical and hormonal effects on behaviour, the neurochemical mechanisms under-lying behaviour, and behavioural methods for the study of drug action. Both animal and human studies are welcome; however, studies reporting neurochemical data should have a predominantly behavioural focus, and human studies should not consist exclusively of clinical trials or case reports. Preference is given to studies that demonstrate and develop the potential of behavioural methods, and to papers reporting findings of direct relevance to clinical problems. Papers making a significant theoretical contribution are particularly welcome and, where possible and merited, space is made available for authors to explore fully the theoretical implications of their findings. Reviews of an area of the literature or at an appropriate stage in the development of an author’s own work are welcome. Commentaries in areas of current interest are also considered for publication, as are Reviews and Commentaries in areas outside behavioural pharmacology, but of importance and interest to behavioural pharmacologists. Behavioural Pharmacology publishes frequent Special Issues on current hot topics. The editors welcome correspondence about whether a paper in preparation might be suitable for inclusion in a Special Issue.