PMID- 29481896
OWN - NLM
STAT- MEDLINE
DCOM- 20190214
LR  - 20220408
IS  - 1878-4216 (Electronic)
IS  - 0278-5846 (Linking)
VI  - 84
IP  - Pt A
DP  - 2018 Jun 8
TI  - Zinc as a therapy in a rat model of autism prenatally induced by valproic acid.
PG  - 173-180
LID - S0278-5846(17)30859-X [pii]
LID - 10.1016/j.pnpbp.2018.02.008 [doi]
AB  - 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.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Cezar, Luana Carvalho
AU  - Cezar LC
AD  - University of Sao Paulo, School of Veterinary Medicine, Department of Pathology, 
      Sao Paulo, Brazil. Electronic address: cezarlc@usp.br.
FAU - Kirsten, Thiago Berti
AU  - Kirsten TB
AD  - Paulista University, Environmental and Experimental Pathology, Sao Paulo, Brazil.
FAU - da Fonseca, Caio Cesar Navarrete
AU  - da Fonseca CCN
AD  - Federal University of Sao Paulo, Department of Morphology and Genetics, Sao 
      Paulo, Brazil.
FAU - de Lima, Ana Paula Nascimento
AU  - de Lima APN
AD  - University of Sao Paulo, School of Veterinary Medicine, Department of Pathology, 
      Sao Paulo, Brazil.
FAU - Bernardi, Maria Martha
AU  - Bernardi MM
AD  - Paulista University, Environmental and Experimental Pathology, Sao Paulo, Brazil.
FAU - Felicio, Luciano Freitas
AU  - Felicio LF
AD  - University of Sao Paulo, School of Veterinary Medicine, Department of Pathology, 
      Sao Paulo, Brazil.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180223
PL  - England
TA  - Prog Neuropsychopharmacol Biol Psychiatry
JT  - Progress in neuro-psychopharmacology & biological psychiatry
JID - 8211617
RN  - 0 (Neuroprotective Agents)
RN  - 614OI1Z5WI (Valproic Acid)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - J41CSQ7QDS (Zinc)
SB  - IM
MH  - Animals
MH  - Autistic Disorder/*prevention & control
MH  - Corpus Striatum/drug effects/growth & development/metabolism
MH  - Disease Models, Animal
MH  - Female
MH  - Male
MH  - Neuroprotective Agents/*pharmacology
MH  - Pregnancy
MH  - *Prenatal Exposure Delayed Effects
MH  - Rats, Wistar
MH  - Social Behavior
MH  - Tyrosine 3-Monooxygenase/metabolism
MH  - Ultrasonics
MH  - Valproic Acid/*toxicity
MH  - Vocalization, Animal/drug effects
MH  - Zinc/*pharmacology
OTO - NOTNLM
OT  - Animal model
OT  - Autistic-like behavior
OT  - Dopamine
OT  - Valproic acid
OT  - Zinc deficiency
EDAT- 2018/02/27 06:00
MHDA- 2019/02/15 06:00
CRDT- 2018/02/27 06:00
PHST- 2017/10/11 00:00 [received]
PHST- 2018/02/05 00:00 [revised]
PHST- 2018/02/17 00:00 [accepted]
PHST- 2018/02/27 06:00 [pubmed]
PHST- 2019/02/15 06:00 [medline]
PHST- 2018/02/27 06:00 [entrez]
AID - S0278-5846(17)30859-X [pii]
AID - 10.1016/j.pnpbp.2018.02.008 [doi]
PST - ppublish
SO  - Prog Neuropsychopharmacol Biol Psychiatry. 2018 Jun 8;84(Pt A):173-180. doi: 
      10.1016/j.pnpbp.2018.02.008. Epub 2018 Feb 23.