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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Cezar, Luana Carvalho [1] ; Kirsten, Thiago Berti [2] ; Navarrete da Fonseca, Caio Cesar [3] ; Nascimento de Lima, Ana Paula [1] ; Bernardi, Maria Martha [2] ; Felicio, Luciano Freitas [1]
Total Authors: 6
Affiliation:
[1] Univ Sao Paulo, Sch Vet Med, Dept Pathol, Ave Prof Dr Orlando Marques da Paiva 87, Sao Paulo - Brazil
[2] Univ Paulista, Environm & Expt Pathol, Sao Paulo - Brazil
[3] Univ Fed Sao Paulo, Dept Morphol & Genet, Sao Paulo - Brazil
Total Affiliations: 3
Document type: Journal article
Source: PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY; v. 84, n. A, p. 173-180, JUN 8 2018.
Web of Science Citations: 6
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. (AU)

FAPESP's process: 13/01610-7 - Subsistence and reproduction: opioidergic modulation of behavioral selection during lactation
Grantee:Luciano Freitas Felicio
Support type: Regular Research Grants