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

Fiorella Malchiodi-Albedi, Tamara C. Petrucci, Barbara Picconi, Francesca Iosi, Mario Falchi

Research output: Contribution to journalArticlepeer-review

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 - 32UP-;abeled 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 provide a potential link between the biochemical hallmark of AD (hyperphosphorylation of tau) and a pathological finding of primary clinical relevance (the synaptic loss).

Original languageEnglish
Pages (from-to)425-438
Number of pages14
JournalJournal of Neuroscience Research
Volume48
Issue number5
DOIs
Publication statusPublished - Jun 1 1997

Keywords

  • Alzheimer's disease
  • Caliculin A
  • cytoskeleton
  • okadaic acid
  • synaptic proteins

ASJC Scopus subject areas

  • Neuroscience(all)

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