In vivo phosphorylation in the rat basal nucleus induces PHF-like and APP immunoreactivity.
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.
Arendt
T
T
Department of Neurochemistry, Paul Flechsig Institute for Brain Research, University of Leipzig, Germany.
Hanisch
F
F
Holzer
M
M
Brückner
M K
MK
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*
D016564:Amyloid beta-Protein Precursor; D004988:Ethers, Cyclic; D008869:Microtubule-Associated Proteins; D016875:tau Proteins; D019319:Okadaic Acid