Expression of Amyloid precursor protein, tau and presenilin RNAs in rat hippocampus following deafferentation lesions

In this study, entorhinal cortex lesions and/or medial septal area choliner gic lesions were used in the rat to mimic some of the principal and earlies t affects in Alzheimer's disease, namely hippocampal deafferentation. We wi shed to test the hypothesis that deafferentation lesions cause changes in t he 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 subf ields of hippocampus when examined 1 week after entorhinal cortex Lesion, b ur was reduced. compared to sham operated controls, after medial septal are a cholinergic lesions. Cholinergic lesions were combined with entorhinal co rtex lesions and produced no change in APP mRNA levels compared to controls . No significant changes were observed in the parietal cortex after entorhi nal cortex or cholinergic lesions either alone or in combination. Tau mRNA level in hippocampus was unchanged after lesions. Presenilin-1 mRNA was exp ressed 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 differentia lly affected by glutamatergic and cholinergic afferent input, and that pres enilin-1, but not tau, may be subject to the same type of control in vivo. (C) 2001 Elsevier Science B.V. All rights reserved.