PMID- 30144942
OWN - NLM
STAT- MEDLINE
DCOM- 20181211
LR  - 20181211
IS  - 1532-2785 (Electronic)
IS  - 0143-4179 (Linking)
VI  - 71
DP  - 2018 Oct
TI  - Maternal voluntary exercise ameliorates learning deficit in rat pups exposed, in 
      utero, to valproic acid; role of BDNF and VEGF and their receptors.
PG  - 43-53
LID - S0143-4179(18)30041-6 [pii]
LID - 10.1016/j.npep.2018.06.006 [doi]
AB  - In utero exposure to therapeutic doses of valproic acid (VPA) during pregnancy 
      can produce physical malformation and CNS abnormalities in the offspring. There 
      is evidence indicating that even lower doses of VPA during pregnancy could cause 
      cognitive impairment in offspring. It has been demonstrated that maternal 
      exercise has positive effects on offspring's cognitive function. In this study we 
      evaluated the preventive potential of maternal voluntary exercise on cognitive 
      deficits induced by in utero exposure to VPA, in rat pups. Furthermore, the 
      alteration of hippocampal brain-derived neurotrophic factor (BDNF) and vascular 
      endothelial growth factor (VEGF) and their respective receptors were measured. In 
      treatment groups, pregnant rats received VPA (10 and 20 mg/kg) daily on the 
      gestation days (GD) 7 for twelve days with or without access to a running wheel. 
      In control groups, rats received saline with or without access to a running 
      wheel. On postnatal day (PND) 30, learning and memory of rat pups were assessed 
      using the Morris Water Maze (MWM) task. Also, on PND 30, hippocampal BDNF and 
      VEGF were measured by ELISA and western blot analysis respectively. VEGFR (VEGF 
      receptor) and TrkB (Tyrosine receptor kinase B, the receptor for BDNF) 
      expressions were assessed using immunofluorescence staining. Results revealed 
      that maternal voluntary exercise enhanced learning in offspring but had little 
      effect on memory retention. Exposure to VPA during pregnancy disturbed learning 
      and memory in rat pups. Maternal voluntary exercise could ameliorate some aspects 
      of cognitive deficit induced by VPA. TrkB and VEGFR2 expression were enhanced in 
      pups from running mothers. VPA, at both doses, suppressed exercise induced 
      expression of these two receptors. Voluntary exercise and to a much greater 
      extent VPA administration increased hippocampal BDNF. Voluntary exercise of 
      mothers caused an enhance expression of VEGF in rat pups as did VPA 
      administration, although to a smaller amount.
CI  - Copyright (c) 2018. Published by Elsevier Ltd.
FAU - Rahimi, R
AU  - Rahimi R
AD  - Department of Pharmacology, School of Medicine, Iran University for Medical 
      Sciences, Tehran, Iran.
FAU - Akhavan, M M
AU  - Akhavan MM
AD  - Department of Pharmacology, School of Medicine, Iran University for Medical 
      Sciences, Tehran, Iran.
FAU - Kamyab, K
AU  - Kamyab K
AD  - Department of Pathology, Razi Skin Hospital, Tehran University of Medical 
      Sciences, Iran.
FAU - Ebrahimi, S A
AU  - Ebrahimi SA
AD  - Department of Pharmacology, School of Medicine, Iran University for Medical 
      Sciences, Tehran, Iran.. Electronic address: ebrahimi.sa@iums.ac.ir.
LA  - eng
PT  - Journal Article
DEP - 20180630
PL  - Netherlands
TA  - Neuropeptides
JT  - Neuropeptides
JID - 8103156
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 614OI1Z5WI (Valproic Acid)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.10.1 (Receptors, Vascular Endothelial Growth Factor)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/physiology
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Cognition/drug effects
MH  - Female
MH  - Learning/*drug effects
MH  - Male
MH  - Maze Learning/drug effects
MH  - Physical Conditioning, Animal/*physiology
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/*metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor, trkB/metabolism
MH  - Receptors, Vascular Endothelial Growth Factor/metabolism
MH  - Valproic Acid/*pharmacology
MH  - Vascular Endothelial Growth Factor A/*metabolism
OTO - NOTNLM
OT  - Brain-derived neurotrophic factor
OT  - Cognitive dysfunction
OT  - Hippocampus
OT  - Maternal voluntary exercise
OT  - Valproate
OT  - Vascular endothelial growth factor
OT  - Water maze
EDAT- 2018/08/27 06:00
MHDA- 2018/12/12 06:00
CRDT- 2018/08/27 06:00
PHST- 2018/02/26 00:00 [received]
PHST- 2018/05/16 00:00 [revised]
PHST- 2018/06/28 00:00 [accepted]
PHST- 2018/08/27 06:00 [pubmed]
PHST- 2018/12/12 06:00 [medline]
PHST- 2018/08/27 06:00 [entrez]
AID - S0143-4179(18)30041-6 [pii]
AID - 10.1016/j.npep.2018.06.006 [doi]
PST - ppublish
SO  - Neuropeptides. 2018 Oct;71:43-53. doi: 10.1016/j.npep.2018.06.006. Epub 2018 Jun 
      30.