The formation of PHF-1 and SMI-31 positive dystrophic neurites in rat hippocampus following acute injection of okadaic acid

Within neurofibrillary tangles and dystrophic neurites of Alzheimer's disea se (AD), tau protein is hyperphosphorylated. in the present study, we provi de evidence that acute injection of okadaic acid (1 mM, 0.5 mu l) into the dorsal hippocampus induces the formation of paired helical filament (PHF)-1 , Sternberger monoclonals incorporated (SMI)-31, and amyloid precursor prot ein (APP) positive dystrophic neurites in the lacunosum-molecular layer of CA1 and molecular layer of dentate gyrus. Okadaic acid evoked a marked loss of microtubule associated protein (MAP)-2 immunoreactivity, PHF-1 immunore active terminals were fine, and SMI-31 immunoreactive terminals appeared at granular terminals and at the ring-like or elongated dystrophic neu rites. APP positive dystrophic neu rites exhibited large bu Ib-like globular term inals. Interestingly, APP dystrophic neurites were co-localized with SMI-31 immunoreactivity in the core. APP immunoreactivity became stronger over 24 h even in vehicle injected area. These results may provide the morpho logi cal evidence for the animal model to study dystrophic neurites formation of AD. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.