title: Inhibition of MAPK/ERK signaling blocks hippocampal neurogenesis and impairs cognitive performance in prenatally infected neonatal rats.
abstract: Hippocampus endogenous neurogenesis has been postulated to play a favorable role in brain restoration after injury. However, the underlying molecular mechanisms have been insufficiently deciphered. Here we investigated the potential regulatory capacity of MAPK/ERK signaling on neurogenesis and the associated cognitive performance in prenatally infected neonatal rats. From our data, intrauterine infection could induce hippocampal neuronal apoptosis and promote endogenous repair by evoking neural stem cell proliferation and survival. We also found intrauterine infection could induce increased levels of p-ERK, p-CREB and BDNF, which might be responsible for the potential endogenous rescue system. Furthermore, inhibition of MAPK/ERK signaling could aggravate hippocampal neuronal apoptosis, decrease neurogenesis, and impair the offspring's cognitive performances and could also down-regulate the levels of p-ERK, p-CREB and BDNF. Our data strongly suggest that the activation of MAPK/ERK signaling may play a significant role in promoting survival of newly generated neural stem cells via an anti-apoptotic mechanism, which may be particularly important in endogenous neuroprotection associated with cognitive performance development in prenatally infected rats.
authors.affiliation: Department of Neurology, Children's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Peifang
authors.initials: P
authors.lastname: Jiang
authors.forename: Tao
authors.initials: T
authors.lastname: Zhu
authors.forename: Zhezhi
authors.initials: Z
authors.lastname: Xia
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Weizhong
authors.initials: W
authors.lastname: Gu
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Tianming
authors.initials: T
authors.lastname: Yuan
authors.forename: Huimin
authors.initials: H
authors.lastname: Yu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002070:Butadienes / Q000494:pharmacology; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004927:Escherichia coli Infections / Q000150:complications / Q000473:pathology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D009570:Nitriles / Q000494:pharmacology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000473:pathology*; D051381:Rats
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D002070:Butadienes; D017362:Cyclic AMP Response Element-Binding Protein; D004791:Enzyme Inhibitors; D009570:Nitriles; C113580:U 0126; D048049:Extracellular Signal-Regulated MAP Kinases