The comparative effectiveness of metformin and risperidone in a rat model of valproic acid-induced autism, Potential role for enhanced autophagy.
Rationale: Risperidone is the first antipsychotic to be approved by Food and Drug Administration (FDA) for treating autism spectrum disorder (ASD). The potential efficacy of metformin in preventing and/or controlling ASD behavioral deficits was also recently reported. Suppression of hippocampus auto...
| Publicado en: | Psychopharmacology Vol. 240; no. 6; pp. 1313 - 1333 |
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| Autores principales: | , , , , |
| Formato: | Journal Article |
| Publicado: |
Springer Nature
Jun2023
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=163723336&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 163723336 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00333158 EJD jtl: Psychopharmacology issn: 00333158 maglogo: N pubinfo: dt: Jun2023 vid: 240 iid: 6 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 163723336 163480496 10.1007/s00213-023-06371-1 163723336 ppf: 1313 ppct: 20 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: The comparative effectiveness of metformin and risperidone in a rat model of valproic acid-induced autism, Potential role for enhanced autophagy. aug: au: Atia, Amany AA Ashour, Rehab H Zaki, Marwa MAF Rahman, Karawan MA Ramadan, Nehal M affil: Department of Clinical Pharmacology, Faculty of Medicine, Mansoura University, 60 El-Gomhoria Street, 35516, Mansoura, Al-Dakahlia, Egypt sug: ab: Rationale: Risperidone is the first antipsychotic to be approved by Food and Drug Administration (FDA) for treating autism spectrum disorder (ASD). The potential efficacy of metformin in preventing and/or controlling ASD behavioral deficits was also recently reported. Suppression of hippocampus autophagy was suggested as a potential pathologic mechanism in ASD. Objectives: Is metformin's ability to improve ASD clinical phenotype driven by its autophagy-enhancing properties? And does hippocampus autophagy enhancement underlie risperidone's efficacy as well? Both questions are yet to be answered. Methods: The effectiveness of metformin on alleviation of ASD-like behavioral deficits in adolescent rats exposed prenatally to valproic acid (VPA) was compared to that of risperidone. The potential modulatory effects of risperidone on hippocampal autophagic activity were also assessed and compared to those of metformin. Results: Male offspring exposed to VPA during gestation exhibited marked anxiety, social impairment and aggravation of stereotyped grooming; such deficits were efficiently rescued by postnatal risperidone or metformin therapy. This autistic phenotype was associated with suppressed hippocampal autophagy; as evidenced by reduced gene/dendritic protein expression of LC3B (microtubule-associated proteins 1 light chain 3B) and increased somatic P62 (Sequestosome 1) protein aggregates. Interestingly, compared to risperidone, the effectiveness of metformin in controlling ASD symptoms and improving hippocampal neuronal survival was well correlated to its ability to markedly induce pyramidal neuronal LC3B expression while lowering P62 accumulation. Conclusions: Our work highlights, for the first time, positive modulation of hippocampus autophagy as potential mechanism underlying improvements in autistic behaviors, observed with metformin, as well as risperidone, therapy. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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