title: In vivo phosphorylation in the rat basal nucleus induces PHF-like and APP immunoreactivity.
abstract: In vivo phosphorylation was stimulated in the rat basal nucleus by stereotaxic injection of the phosphatase inhibitor okadaic acid (OA). Hyperphosphorylation of neurofilaments and of the microtubule-associated proteins tau and MAP2 was associated with their redistribution from the axonal compartment into the cell bodies of large projection neurones where they appeared as paired helical filament (PHF)-like immunoreactivity. Astrocytes showed a dramatic increase in APP immunoreactivity and changed their appearance to a stellate shape with long processes. The results demonstrate that abnormal tau phosphorylation and changes in the expression and/or metabolism of APP can be induced in vivo by altering protein phosphorylation. The present experimental paradigm might, therefore, provide a useful tool to model early steps of the pathomechanism of Alzheimer's disease.
authors.affiliation: Department of Neurochemistry, Paul Flechsig Institute for Brain Research, University of Leipzig, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Arendt
authors.forename: F
authors.initials: F
authors.lastname: Hanisch
authors.forename: M
authors.initials: M
authors.lastname: Holzer
authors.forename: M K
authors.initials: MK
authors.lastname: Brückner
mesh_terms: D000544:Alzheimer Disease; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D001479:Basal Ganglia / Q000378:metabolism*; D003599:Cytoskeleton / Q000187:drug effects; D004195:Disease Models, Animal; D004988:Ethers, Cyclic / Q000494:pharmacology* / Q000633:toxicity; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000187:drug effects; D016874:Neurofibrillary Tangles; D019319:Okadaic Acid; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013238:Stereotaxic Techniques; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016564:Amyloid beta-Protein Precursor; D004988:Ethers, Cyclic; D008869:Microtubule-Associated Proteins; D016875:tau Proteins; D019319:Okadaic Acid