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P2‐245: Dysregulation of brain insulin signaling: A mechanistic link between diabetes and Alzheimer's disease
Author(s) -
Gong Cheng-Xin,
Liu Ying,
Deng Yanqiu,
Liu Fei,
Grundke-Iqbal Inge,
Iqbal Khalid
Publication year - 2010
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2010.05.1294
Subject(s) - insulin receptor , protein kinase b , pi3k/akt/mtor pathway , insulin resistance , insulin , gsk 3 , endocrinology , medicine , irs1 , phosphoinositide 3 kinase , insulin receptor substrate , signal transduction , diabetes mellitus , biology , microbiology and biotechnology
disease characterized by memory impairments and cognitive deterioration, numerous aspects of brain plasticity are impaired. For example, we have recently shown that neurogenesis is significantly impaired in the brains of transgenic mice harboring APPswe/PS1DE9. In this study we examined the hypothesis that experience of transgenic mice harboring APPswe/ PS1DE9 in an enriched environment would enhance brain plasticity, manifested in enhanced neurogenesis and hippocampal learning and reduced neuropathology. Methods: Extent of neurogenesis and neuropathology were examined in the brain of young APPswe/PS1DE9 mice that experienced environmental enrichment and/or standard housing condition. Results: We show that experience of APPswe/PS1DE9 mice in enriched environmental conditions upregulates neural progenitor cell proliferation and neural maturation in the dentate gyrus of the hippocampus. Environmental enrichment also reduced levels of soluble oligomeric beta-amyloid peptides and of hyperphosphorylated tau, the precursors of AD hallmarks. Functionally, environmental enrichment significantly enhanced hippocampal LTP, without notable alternation in basal synaptic transmission. In addition, we also observed upregulation of the main anterograde motor protein, kinesin-1, in the brains of these transgenic mice, suggesting the enhancement of axonal transport. Conclusions: This study shows that environmental experience can enhance neuroplasticity, attenuate pathology and enhance synaptic plasticity in transgenic mouse models of AD. This study establishes the high significance of environmental factors and lifestyle in the development of AD.