PMID: 9185666Jun 1, 1997Paper

Protein phosphatase inhibitors induce modification of synapse structure and tau hyperphosphorylation in cultured rat hippocampal neurons

Journal of Neuroscience Research
F Malchiodi-AlbediM Falchi

Abstract

Protein phosphatase inhibitors, okadaic acid and Caliculin A, were used to investigate how perturbation of phosphorylation and dephosphorylation processes might affect neurite and synapse structure in cultures of fetal rat hippocampal neurons. Drug treatments induced neuritic tree modification, with retraction of the processes and the appearance of dilatations along the neurites. The characteristic dotlike pattern of immunoreactivity of synaptic vesicle proteins disappeared. Normal synapses were extremely rare by ultrastructural observation. Vesicles of various diameters accumulated in the dilatations, as did organelles and amorphous material, suggesting impaired axonal transport. Hyperphosphorylation of tau protein was also observed as indicated by the shift in the electrophoretic mobility of a 32P-labeled 55-kDa band and by immunoblot with epitope-specific tau antibody. Our results show that inhibition of protein phosphatases 1 and 2A results in a modification of the neuritic tree structure, with loss of neuronal processes, phosphorylation of a tau isoform, and a decrease in the number of synapses. These neuronal features are present in Alzheimer's disease (AD). Our results suggest that the two events might be related and pro...Continue Reading

Citations

Oct 5, 2001·Learning & Memory·C A Stafstrom-DavisT A Houpt
Apr 29, 2009·International Journal of Molecular Sciences·Rudy J CastellaniGeorge Perry
Jul 21, 1998·Annals of the New York Academy of Sciences·E Friedman, H Y Wang
Oct 26, 2010·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Joshua A HarrillWilliam R Mundy

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