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

摘要

Within neurofibrillary tangles and dystrophic neurites of Alzheimer's disease (AD), tau protein is hyperphosphorylated. In the present study, we provide evidence that acute injection of okadaic acid (1 mM, 0.5 microliter) into the dorsal hippocampus induces the formation of paired helical filament (PHF)-1, sternberger monoclonals incorporated (SMI)-31, and amyloid precursor protein (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 immunoreactive terminals were fine, and SMI-31 immunoreactive terminals appeared at granular terminals and at the ring-like or elongated dystrophic neurites. APP positive dystrophic neurites exhibited large bulb-like globular terminals. 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 morphological evidence for the animal model to study dystrophic neurites formation of AD.