Chronic lurasidone treatment normalizes GABAergic marker alterations in the dorsal hippocampus of mice exposed to prenatal immune activation

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• 作者：A. Luoni^a ; ¹ ; J. Richetto^b ; ¹ ; L. Longo^a ; M.A. Riva^a ; ^{M.Riva@unimi.it}
• 关键词：Poly(I ; C) ; Infection ; GABA ; Hippocampus ; Lurasidone ; BDNF
• 刊名：European Neuropsychopharmacology
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：27
• 期：2
• 页码：170-179
• 全文大小：1071 K
• 卷排序：27

文摘

Prenatal maternal infection represents a risk factor for the development of psychopathologic conditions later in life. Clinical evidence is also supported by animal models in which the vulnerability to develop a schizophrenic-like phenotype likely originates from inflammatory processes as early as in the womb. Prenatal immune challenge, for example, induces a variety of long-term behavioral alterations in mice, such as deficits in recognition and spatial working memory, perseverative behaviors and social impairments, which are relevant to different symptom clusters of schizophrenia.Here, we investigated the modulation of GABAergic markers in the dorsal and ventral hippocampus of adult mice exposed to late prenatal immune challenge with the viral mimetic Poly(I:C) (polyriboinosinic-polyribocytidilic-acid) at gestational day 17, and we evaluated the ability of chronic treatment with the multi-receptor antipsychotic lurasidone to modulate the alterations produced by maternal infection. Poly(I:C) mice show a significant reduction of key GABAergic markers, such as GAD67 and parvalbumin, specifically in the dorsal hippocampus, which were normalized by chronic lurasidone administration. Moreover, chronic drug administration increases the expression of the pool of brain derived neurotrophic factor (BDNF) transcripts with the long 3’-UTR as well as the levels of mature BDNF protein in the synaptosomal compartment, selectively in dorsal hippocampus.All in all, our findings demonstrate that lurasidone is effective in ameliorating molecular abnormalities observed in Poly(I:C) mice, providing further support to the neuroplastic properties of this multi-receptor antipsychotic drug.