Electrical stimulation of cerebellar fastigial nucleus protects rat brain, in vitro, from staurosporine-induced apoptosis

Ping Zhou, Liping Qian, Sara B. Glickstein, Eugene V. Golanov, Virginia M. Pickel, Donald J. Reis

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Electrical stimulation of the cerebellar fastigial nucleus (FN) elicits a prolonged (∼10 days) and substantial (50-80%) protection against ischemic and excitotoxic injuries. The mechanism(s) of protection are unknown. We investigated whether FN stimulation directly protects brain cells against apoptotic cell death in an in vitro rat brain slice culture model. Rats were electrically stimulated in FN or, as control, the cerebellar dentate nucleus (DN). Coronal slices through the forebrain were explanted, exposed to staurosporine, harvested, and analyzed for caspase-3 activity by a fluorescence assay. FN, but not DN, stimulation significantly reduced staurosporine-induced caspase-3 activity by 39 ± 7% at 3 h, 31 ± 3% at 6 h and 26 ± 4% at 10 h of incubation. Immunocytochemistry revealed FN-specific reductions in activated caspase-3 mainly in glial-like cells throughout the forebrain. FN stimulation also results in a 56.5% reduction in cytochrome c release upon staurosporine incubation. We conclude that neuroprotection elicited from FN stimulation can directly modify the sensitivity of brain cells to apoptotic stimuli and thereby suppress staurosporine induced apoptosis in adult rat brain slices. This model indicates that neuroprotection can be studied in vitro and provides new insight into the potential role of glial cells in ischemic protection of neurons induced by FN stimulation.

Original languageEnglish (US)
Pages (from-to)328-338
Number of pages11
JournalJournal of Neurochemistry
Volume79
Issue number2
DOIs
StatePublished - 2001

Keywords

  • Apoptosis
  • Caspases
  • Cerebellar fastigial nucleus
  • Neuroprotection
  • Slice culture
  • Staurosporine

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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