title: Two memory associated genes regulated by amyloid precursor protein intracellular domain: Novel insights into the pathogenesis of learning and memory impairment in Alzheimer's disease.
abstract: In this study, we employed chromatin immunoprecipitation, a useful method for studying the locations of transcription factors bound to specific DNA regions in specific cells, to investigate amyloid precursor protein intracellular domain binding sites in chromatin DNA from hippocampal neurons of rats, and to screen out five putative genes associated with the learning and memory functions. The promoter regions of the calcium/calmodulin-dependent protein kinase II alpha and glutamate receptor-2 genes were amplified by PCR from DNA products immunoprecipitated by amyloid precursor protein intracellular domain. An electrophoretic mobility shift assay and western blot analysis suggested that the promoter regions of these two genes associated with learning and memory were bound by amyloid precursor protein intracellular domain (in complex form). Our experimental findings indicate that the amyloid precursor protein intracellular domain is involved in the transcriptional regulation of learning- and memory-associated genes in hippocampal neurons. These data may provide new insights into the molecular mechanism underlying the symptoms of progressive memory loss in Alzheimer's disease.
authors.affiliation: Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, Guangdong Province, China.
authors.forename: Chuandong
authors.initials: C
authors.lastname: Zheng
authors.affiliation: Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, Guangdong Province, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Gu
authors.affiliation: Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, Guangdong Province, China.
authors.forename: Zhimei
authors.initials: Z
authors.lastname: Zhong
authors.affiliation: Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, Guangdong Province, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhu
authors.affiliation: Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, Guangdong Province, China.
authors.forename: Tianming
authors.initials: T
authors.lastname: Gao
authors.affiliation: Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, Guangdong Province, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
keywords: Alzheimer's disease; amyloid precursor protein; amyloid precursor protein intracellular domain; chromatin DNA; chromatin immunoprecipitation; gene regulation