Environmental enrichment restores cognitive deficits induced by prenatal maternal seizure.
Maternal seizure has adverse effects on brain histology as well as on learning and memory ability in progeny. An enriched environment (EE) is known to promote structural changes in the brain and improve cognitive and motor deficits following a variety of brain injuries. Whether EE treatment in early postnatal periods could restore cognitive impairment induced by prenatal maternal seizure is unknown. Adult female Sprague-Dawley rats were randomly separated into two groups and were injected intraperitoneally either saline or pentylenetetrazol (PTZ) for 30 days. Then the fully kindled rats and control animals were allowed to mate. PTZ administration was continued until delivery, while the control group received saline at the same time. After weaning at postnatal day 22, one-half of the male offspring in the control and in the prenatal maternal group were given the environmental enrichment treatment through all the experiments until they were tested. Morris water maze testing was performed at 8 weeks of age. Western blot and synaptic ultrastructure analysis were then performed. We found that EE treatment reversed spatial learning deficits induced by prenatal maternal seizure. An EE also reversed the changes in synaptic ultrastructure following prenatal maternal seizure. In addition, prenatal maternal seizure significantly decreased phosphorylation states of cAMP response element binding (CREB) in the hippocampus, whereas EE reversed this reduced expression. These findings suggest that EE treatment on early postnatal periods could be a potential therapy for improving cognitive deficits induced by prenatal maternal seizure.
Key Laboratory of Neurology of Hebei Province, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China.
Tao
T
Xie
Wei-ping
WP
Wang
Li-jing
LJ
Jia
Zhuo-feng
ZF
Mao
Zhen-zhen
ZZ
Qu
Shao-qun
SQ
Luan
Min-chen
MC
Kan
D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D050882:CREB-Binding Protein / Q000378:metabolism; D002452:Cell Count; D003072:Cognition Disorders / Q000209:etiology* / Q000473:pathology / Q000628:therapy*; D003292:Convulsants / Q000633:toxicity; D004777:Environment; D004827:Epilepsy / Q000139:chemically induced / Q000401:mortality / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D006624:Hippocampus / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D046529:Microscopy, Electron, Transmission; D010433:Pentylenetetrazole / Q000633:toxicity; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D013997:Time Factors
D019208:Brain-Derived Neurotrophic Factor; D003292:Convulsants; D050882:CREB-Binding Protein; C494365:Crebbp protein, rat; D010433:Pentylenetetrazole