Sex-specific effects of prenatal chronic mild stress on adult spatial learning capacity and regional glutamate receptor expression profiles.
Both animal experiments and clinical studies have demonstrated that prenatal stress can cause cognitive disorders in offspring. To explore the scope of these deficits and identify potential underlying mechanisms, we examined the spatial learning and memory performance and glutamate receptor (GluR) expression patterns of adult rats exposed to prenatal chronic mild stress (PCMS). Principal component analysis (PCA) was employed to reveal the interrelationships among spatial learning indices and GluR expression changes. Female PCMS-exposed offspring exhibited markedly impaired spatial learning and memory in the Morris water maze (MWM) task compared to control females, while PCMS-exposed males showed better initial spatial learning in the MWM compared to control males. PCMS also altered basal and post-MWM glutamate receptor expression patterns, but these effects differed markedly between sexes. Male PCMS-exposed offspring exhibited elevated basal expression of NR1, mGluR5, and mGluR2/3 in the prefrontal cortex (PFC), whereas females showed no basal expression changes. Following MWM training, PCMS-exposed males expressed higher NR1 in the PFC and mammillary body (MB), higher mGluR2/3 in PFC, and lower NR2B in the hippocampus (HIP), PFC, and MB compared to unstressed MWM-trained males. Female PCMS-exposed offspring showed strongly reduced NR1 in MB and NR2B in the HIP, PFC, and MB, and increased mGluR2/3 in PFC compared to unstressed MWM-trained females. This is the first report suggesting that NMDA subunits in the MB are involved in spatial learning. Additionally, PCA further suggests that the NR1-NR2B form is the most important for spatial memory formation. These results reveal long-term sex-specific effects of PCMS on spatial learning and memory performance in adulthood and implicate GluR expression changes within HIP, PFC, and MB as possible molecular mechanisms underlying cognitive dysfunction in offspring exposed to prenatal stress.
Department of Psychiatry, The First Affiliated Hospital of China Medical University, PR China.
Yan
Y
Wang
College of Humanities and Social Sciences, Applied Psychology, China Medical University, PR China.
Yuchao
Y
Ma
Essential Qualities Oriented Education College, Liaoning Finance Vocation College, PR China.
Jingmin
J
Hu
Department of Psychiatry, The First Affiliated Hospital of China Medical University, PR China.
Xinxin
X
Zhang
College of Humanities and Social Sciences, Applied Psychology, China Medical University, PR China.
Wenwen
W
Cheng
Department of Psychiatry, The First Affiliated Hospital of China Medical University, PR China.
Han
H
Jiang
Psychological Counseling Room, Hebei Institute of Foreign Languages, PR China.
Min
M
Li
Center for Mental Health Control and Prevention, The Third People's Hospital of Liaoning, PR China.
Jintao
J
Ren
Department of Psychiatry, The First Affiliated Hospital of China Medical University, PR China.
Xiaosong
X
Zhang
Department of Psychiatry, The First Affiliated Hospital of China Medical University, PR China.
Mengxi
M
Liu
Department of Psychiatry, The First Affiliated Hospital of China Medical University, PR China.
Anji
A
Sun
Department of Psychiatry, The First Affiliated Hospital of China Medical University, PR China.
Qi
Q
Wang
Department of Psychiatry, The First Affiliated Hospital of China Medical University, PR China. Electronic address: xbli@mail.cmu.edu.cn.
Xiaobai
X
Li
D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005508:Food Deprivation; D007859:Learning Disabilities / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000378:metabolism*; D012727:Sex Characteristics; D065853:Spatial Learning / Q000502:physiology*; D013312:Stress, Physiological; D014868:Water Deprivation
D017470:Receptors, Glutamate
Gender difference; Glutamate receptor; Hippocampus; Learning and memory; Mammillary body; Prefrontal cortex; Prenatal stress