Exposure to social defeat stress in adolescence improves the working memory and anxiety-like behavior of adult female rats with intrauterine growth restriction, independently of hippocampal neurogenesis.
Intrauterine growth restriction (IUGR) is a risk factor for memory impairment and emotional disturbance during growth and adulthood. However, this risk might be modulated by environmental factors during development. Here we examined whether exposing adolescent male and female rats with thromboxane A2-induced IUGR to social defeat stress (SDS) affected their working memory and anxiety-like behavior in adulthood. We also used BrdU staining to investigate hippocampal cellular proliferation and BrdU and NeuN double staining to investigate neural differentiation in female IUGR rats. In the absence of adolescent stress, IUGR female rats, but not male rats, scored significantly lower in the T-maze test of working memory and exhibited higher anxiety-like behavior in the elevated-plus maze test compared with controls. Adolescent exposure to SDS abolished these behavioral impairments in IUGR females. In the absence of adolescent stress, hippocampal cellular proliferation was significantly higher in IUGR females than in non-IUGR female controls and was not influenced by adolescent exposure to SDS. Hippocampal neural differentiation was equivalent in non-stressed control and IUGR females. Neural differentiation was significantly increased by adolescent exposure to SDS in controls but not in IUGR females. There was no significant difference in the serum corticosterone concentrations between non-stressed control and IUGR females; however, adolescent exposure to SDS significantly increased serum corticosterone concentration in control females but not in IUGR females. These results demonstrate that adolescent exposure to SDS improves behavioral impairment independent of hippocampal neurogenesis in adult rats with IUGR.
Department of Physiology, St. Marianna University School of Medicine, Kawasaki, Japan; Department of Mental Disorder, National Center of Psychiatry and Neuroscience, Tokyo, Japan. Electronic address: mfuruta@marianna-u.ac.jp.
Miyako
M
Furuta
Department of Mental Disorder, National Center of Psychiatry and Neuroscience, Tokyo, Japan.
Midori
M
Ninomiya-Baba
Department of Mental Disorder, National Center of Psychiatry and Neuroscience, Tokyo, Japan.
Shuichi
S
Chiba
Department of Physiology, St. Marianna University School of Medicine, Kawasaki, Japan.
Toshiya
T
Funabashi
Department of Physiology, St. Marianna University School of Medicine, Kawasaki, Japan.
Tatsuo
T
Akema
Department of Mental Disorder, National Center of Psychiatry and Neuroscience, Tokyo, Japan.
Hiroshi
H
Kunugi
D000818:Animals; D001007:Anxiety / Q000523:psychology*; D001522:Behavior, Animal / Q000502:physiology*; D001835:Body Weight; D002454:Cell Differentiation; D049109:Cell Proliferation; D003345:Corticosterone / Q000097:blood; D005260:Female; D005317:Fetal Growth Retardation / Q000523:psychology*; D006624:Hippocampus / Q000196:embryology / Q000254:growth & development*; D008570:Memory, Short-Term / Q000502:physiology*; D011247:Pregnancy; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D012931:Social Environment; D013315:Stress, Psychological / Q000523:psychology*
D003345:Corticosterone
Anxiety-like behavior; Female rat; Hippocampal cellular proliferation; Hippocampal neurogenesis; Intrauterine growth restriction; Social defeat stress; Working memory