title: Prenatal stress disturbs hippocampal KIF17 and NR2B in spatial cognition in male offspring.
abstract: Numerous studies have demonstrated that prenatal stress disturbs the hippocampal-mediated learning and memory processes in offspring. The underlying mechanisms for this effect, however, remain vague. It is well documented that N-methyl-D-aspartate (NMDA) receptors play a pivotal role in learning and memory, which are related to dynamically trafficking and regulating NMDA receptors by their response motor proteins. Over the past few years, increasing numbers of studies have elucidated that hippocampal-mediated learning and memory are regulated by KIF17 (kinesin superfamily motor protein 17), which specifically transports and regulates the NMDA receptor subunit NR2B in hippocampal neurons. The present study shows the influence of prenatal stress on KIF17 and NR2B expression and hippocampal NR2A/NR2B ratio partially reflecting function of KIF17, using mice as models. It was found that prenatal stress significantly decreased the hippocampal KIF17 and NR2B level in offspring at postnatal stages of 3 weeks and 9 weeks. Moreover, hippocampal KIF17 in the prenatally stressed pups continued to be weakened even after serial Morris water maze trainings, but not NR2B. Finally, the synaptic NR2A/NR2B level was upregulated in offspring exposed to prenatal stress, which revealed the dysfunction of KIF17. Thus, we conclude that prenatal stress leads to long-lasting deterioration of the expression and function of hippocampal KIF17 in offspring, which may be related to deficits of spatial cognition caused by prenatal stress. These data underpin the hypotheses that a physiopathology of neurodevelopmental origin in early life leads to defects in learning and memory in later life.
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Tongji University, Shanghai, People's Republic of China.
authors.forename: Depeng
authors.initials: D
authors.lastname: Zhao
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.forename: Xueyu
authors.initials: X
authors.lastname: Chen
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.forename: Ai
authors.initials: A
authors.lastname: Zhang
authors.forename: Jiuhong
authors.initials: J
authors.lastname: Kang
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhou
authors.forename: Tao
authors.initials: T
authors.lastname: Duan
mesh_terms: D000818:Animals; D005260:Female; D006624:Hippocampus / Q000378:metabolism*; D016547:Kinesins / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013312:Stress, Physiological / Q000502:physiology*
chemical_list: C409642:KIF17 protein, mouse; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D016547:Kinesins