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P4‐023: PPAR‐gamma agonism promotes the formation of a nuclear pERK‐PPAR‐gamma complex that mediates cognitive rescue in Tg2576 Alzheimer's mice
Author(s) -
Jahrling Jordan,
Denner Larry,
Dineley Kelly
Publication year - 2012
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.2012.05.1724
Subject(s) - hippocampus , hippocampal formation , neuroscience , mapk/erk pathway , psychology , memory consolidation , cognitive decline , medicine , biology , signal transduction , dementia , disease , microbiology and biotechnology
enhanced spatial learning and memory performance. Further, amyloid-beta injection to rat CA1 area impaired spatial learning and memory; it also markedly decreased the expression level of the NMDA receptor subunits NR1 and NR2B. Meanwhile, it significantly increased the expression level of STAT1. Transfection of NR1 siRNA and NR2B siRNA both increased the expression of STAT1 at the same time that it decreased the expression of NR1 and NR2B, respectively. Further, transfection of STAT1 siRNA to rat CA1 area rescued amyloid-beta induced spatial memory impairment. Moreover, overexpression of NR1 and NR2B plasmids to CA1 area reversed amyloid-beta induced spatial memory impairment; it also reversed amyloidbeta induced elevation of STAT1 expression.Conclusions: These results together suggest that amyloid-beta impairs water maze performance through decreased expression of NR1 and NR2B that consequently leads to increased expression of STAT1, whereas STAT1 plays an inhibitory role on spatial memory formation. The downstream genes that are regulated by STAT1 involved in spatial memory are currently under investigation.