Zinc as a therapy in a rat model of autism prenatally induced by valproic acid

Zinc as a therapy in a rat model of autism prenatally induced by valproic acid

Author Cezar, Luana Carvalho Google Scholar
Kirsten, Thiago Berti Google Scholar
Fonseca, Caio Cesar Navarrete da Autor UNIFESP Google Scholar
Lima, Ana Paula Nascimento de Google Scholar
Bernardi, Maria Martha Google Scholar
Felicio, Luciano Freitas Google Scholar
Abstract Autism is characterized by numerous behavioral impairments, such as in communication, socialization and cognition. Recent studies have suggested that valproic acid (VPA), an anti-epileptic drug with teratogenic activity, is related to autism. In rodents, VPA exposure during pregnancy induces autistic-like effects. Exposure to VPA may alter zinc metabolism resulting in a transient deficiency of zinc. Therefore, we selected zinc as a prenatal treatment to prevent VPA-induced impairments in a rat model of autism. Wistar female rats received either saline solution or VPA (400 mg/kg, i.p) on gestational day (GD) 12.5. To test the zinc supplementation effect, after 1 h of treatment with saline or VPA, a dose of zinc (2 mg/kg, s.c.) was injected. The offspring were tested for abnormal communication behaviors with an ultrasound vocalization task on postnatal day (PND) 11, repetitive behaviors and cognitive ability with a T-maze task on PND 29, and social interaction with a play behavior task on PND 30. Tyrosine hydroxylase protein (TH) expression was evaluated in the striatum. Prenatal VPA decreased ultrasonic vocalization, induced repetitive/restricted behaviors and cognitive inflexibility, impaired socialization, and reduced striatal TH levels compared with control group. Zinc treatment reduced VPA-induced autistic-like behaviors. However, we found no evidence of an effect of zinc on the VPA-induced reduction in TH expression. The persistence of low TH expression in the VPA-Zn group suggests that Zn-induced behavioral improvement in autistic rats may not depend on TH activity.
Keywords Valproic acid
Zinc deficiency
Animal model
Autistic-like behavior
Dopamine
Language English
Sponsor National Council for the Improvement of Higher Education (CAPES)
Foundation for Research Support of Sao Paulo State (FAPESP)
Grant number CAPES: 1454914
FAPESP: 2013/01610-7
Date 2018
Published in Progress In Neuro-Psychopharmacology & Biological Psychiatry. Oxford, v. 84, p. 173-180, 2018.
ISSN 0278-5846 (Sherpa/Romeo, impact factor)
Publisher Pergamon-Elsevier Science Ltd
Extent 173-180
Origin http://dx.doi.org/10.1016/j.pnpbp.2018.02.008
Access rights Closed access
Type Article
Web of Science ID WOS:000429000300019
URI http://repositorio.unifesp.br/handle/11600/45978

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