title: proNGF inhibits neurogenesis and induces glial activation in adult mouse dentate gyrus.
abstract: Recent studies have shown that the precursor of nerve growth factor (proNGF) is highly elevated in aging brains and in the brains of patients with Alzheimer's Disease. proNGF accumulates in hippocampus which is an important neurogenic region related to learning and memory. However, it remains unclear whether proNGF has an influence on hippocampal neurogenesis. In this study, we demonstrated that the high-affinity receptor of proNGF, p75 neurotrophic factor (p75NTR), was expressed both on cells undergoing mitosis and postmitotic mature cells in mouse hippocampus. proNGF infusion into adult mouse hippocampus significantly reduced the density of BrdU-incorporating cells and the density of BrdU/Doublecortin double positive cells in the subgranular zone of hippocampus, indicating an inhibitory effect of proNGF on hippocampal neurogenesis. proNGF infusion also induced prominent cell apoptosis and activated residential astrocyte and microglia, which might further impair the hippocampal neurogenesis. These results implied that proNGF played a pivotal role in regulating the hippocampal neurogenesis and might account for the memory deficit and cognitive impairment.
authors.affiliation: Neurobiology Laboratory, Jiangsu Center for Drug Screening, China Pharmaceutical University, 24# Tongjiaxiang, Nanjing, 210009, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Guo
authors.forename: Jianing
authors.initials: J
authors.lastname: Wang
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
authors.forename: Mingming
authors.initials: M
authors.lastname: Chen
authors.forename: Tao
authors.initials: T
authors.lastname: Pang
authors.forename: Luyong
authors.initials: L
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Liao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001483:Base Sequence; D049109:Cell Proliferation; D017931:DNA Primers; D018891:Dentate Gyrus / Q000166:cytology*; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020932:Nerve Growth Factor / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology*; D009457:Neuroglia / Q000166:cytology*; D011498:Protein Precursors / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D011498:Protein Precursors; C489226:pro-nerve growth factor, mouse; D020932:Nerve Growth Factor