Maternal stress produces learning deficits associated with impairment of NMDA receptor-mediated synaptic plasticity.
Stress in adulthood can have a profound effect on physiology and behavior, but the extent to which prolonged maternal stress affects the brain function of offspring when they are adult remains primarily unknown. In the present work, chronic immobilization stress to pregnant mice affected fetal growth and development. When pups born from stressed mice were reared to adulthood in an environment identical to that of nonstressed controls, several physiological parameters were essentially unaltered. However, spatial learning and memory was significantly impaired in the maternally stressed offspring in adulthood. Furthermore, electrophysiological examination revealed a significant reduction in NMDA receptor-mediated long-term potentiation in the CA1 area of hippocampal slices. Subsequent biochemical analysis demonstrated a substantial decrease in NR1 and NR2B subunits of the NMDA receptor in synapses of the hippocampus, and the interaction between these two subunits appeared to be reduced. These results suggest that prolonged maternal stress leads to long-lasting malfunction of the hippocampus, which extends to and is manifested in adulthood.
School of Biological Sciences, Seoul National University, Seoul 151-742, Korea.
Gi Hoon
GH
Son
Dongho
D
Geum
Sooyoung
S
Chung
Eun Joo
EJ
Kim
Ji-Hoon
JH
Jo
Chang-Mee
CM
Kim
Kun Ho
KH
Lee
Hyun
H
Kim
Sukwoo
S
Choi
Hyun Taek
HT
Kim
Chang-Joong
CJ
Lee
Kyungjin
K
Kim
D000818:Animals; D000831:Animals, Newborn; D005260:Female; D006624:Hippocampus / Q000254:growth & development / Q000378:metabolism / Q000503:physiopathology*; D007859:Learning Disabilities / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D017774:Long-Term Potentiation / Q000502:physiology; D008297:Male; D008569:Memory Disorders / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008813:Mice, Inbred ICR; D009473:Neuronal Plasticity / Q000502:physiology; D009924:Organ Culture Techniques; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism / Q000503:physiopathology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000378:metabolism / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000502:physiology*
C409466:NR1 NMDA receptor; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate