title: The effect of constitutive over-expression of insulin-like growth factor 1 on the cognitive function in aged mice.
abstract: The neurotrophic factor insulin-like growth factor (IGF)-1 promotes neurogenesis in the mammalian brain and provides protection against brain injury. However, studies regarding the effects of IGF-1 on cognitive function in aged mice remain limited. We investigated the effects of overexpression of IGF-1 specifically in neural stem cells of the hippocampal dentate gyrus on the recognitive function in 18-month-old transgenic mice. Immunohistocytochemistry and Nissl staining revealed the increased population of BrdU-positive cells as well as the upregulated expression of Nestin and neuronal nuclei (NeuN), respective markers for neural progenitors and neurons, in the hippocampus of the aged IGF-1 transgenic mice versus the wild-type, suggesting that IGF-1 overexpression promotes neurogenesis. In addition, the IGF-1 receptor (IGF-1R), the phosphorylation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and extracellular signal-regulated kinase (ERK) were enhanced in the transgenic mice than in the wild-type. Transgenic mice also showed superior performance in the Morris water maze and step-down memory tests to their wild-type counterparts. Moreover, the learning and memory abilities of transgenic mice were significantly undermined with the blockage of CaMKII and ERK signaling pathway. Accordingly, our findings indicated that IGF-1 may mitigate the aged-associated cognitive decline via promoting neurogenesis in the hippocampus and activating CaMKII and ERK signaling by binding with IGF-1R.
authors.affiliation: Laboratory Animal Center, Xuzhou Medical College, Xuzhou 221004, Jiangsu, China.
authors.forename: Ankang
authors.initials: A
authors.lastname: Hu
authors.affiliation: Research Center for Neurobiology, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Honghua
authors.initials: H
authors.lastname: Yuan
authors.affiliation: Laboratory Animal Center, Xuzhou Medical College, Xuzhou 221004, Jiangsu, China.
authors.forename: Lianlian
authors.initials: L
authors.lastname: Wu
authors.affiliation: Laboratory Animal Center, Xuzhou Medical College, Xuzhou 221004, Jiangsu, China.
authors.forename: Renjin
authors.initials: R
authors.lastname: Chen
authors.affiliation: Laboratory Animal Center, Xuzhou Medical College, Xuzhou 221004, Jiangsu, China.
authors.forename: Quangang
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Research Center for Neurobiology, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Tengye
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Research Center for Neurobiology, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Research Center for Neurobiology, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.affiliation: Laboratory Animal Center, Xuzhou Medical College, Xuzhou 221004, Jiangsu, China. Electronic address: zxr1967@126.com.
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Zhu
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D003071:Cognition / Q000502:physiology*; D018891:Dentate Gyrus / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015870:Gene Expression; D006624:Hippocampus / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D018782:Maze Learning; D008568:Memory / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000378:metabolism; D055495:Neurogenesis; D009474:Neurons / Q000378:metabolism; D010766:Phosphorylation; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Aged mice; Cognitive ability; Hippocampus; IGF-1; p-CaMKII; p-ERK1/2