title: Expression of amyloid precursor protein, tau and presenilin RNAs in rat hippocampus following deafferentation lesions.
abstract: In this study, entorhinal cortex lesions and/or medial septal area cholinergic lesions were used in the rat to mimic some of the principal and earliest affects in Alzheimer's disease, namely hippocampal deafferentation. We wished to test the hypothesis that deafferentation lesions cause changes in the regulation of three proteins that are known to be important in Alzheimer's disease pathology, namely amyloid precursor protein, presenilin and tau. Expression of amyloid precursor protein mRNA was increased in several subfields of hippocampus when examined 1 week after entorhinal cortex lesion, but was reduced, compared to sham operated controls, after medial septal area cholinergic lesions. Cholinergic lesions were combined with entorhinal cortex lesions and produced no change in APP mRNA levels compared to controls. No significant changes were observed in the parietal cortex after entorhinal cortex or cholinergic lesions either alone or in combination. Tau mRNA level in hippocampus was unchanged after lesions. Presenilin-1 mRNA was expressed in the hippocampus at very low levels, and appeared to be increased following entorhinal cortex lesion. Our results support the hypothesis that amyloid precursor protein expression in hippocampal neurons is differentially affected by glutamatergic and cholinergic afferent input, and that presenilin-1, but not tau, may be subject to the same type of control in vivo.
authors: Biochemical Neuropharmacology Group, Centre for Neuroscience Research, GKT School of Biomedical Sciences, King's College London, Hodgkin Building, Guy's Hospital Campus, SE1 1UL, London, UK.
authors: M J
authors: MJ
authors: Ramirez
authors: K E
authors: KE
authors: Heslop
authors: P T
authors: PT
authors: Francis
authors: M
authors: M
authors: Rattray
mesh_terms: D000110:Acetylcholinesterase / Q000032:analysis; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D015415:Biomarkers; D002799:Cholinergic Fibers / Q000473:pathology; D003714:Denervation; D004195:Disease Models, Animal; D018728:Entorhinal Cortex / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D017403:In Situ Hybridization; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D053764:Presenilin-1; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D016875:tau Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D053764:Presenilin-1; D012333:RNA, Messenger; D016875:tau Proteins; D000110:Acetylcholinesterase