Progressive degeneration of dopamine neurons in 6-hydroxydopamine rat model of Parkinson's disease does not involve activation of caspase-9 and caspase-3

Allison D. Ebert, Jae Hann Hoo, Martha C. Bohn

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

6-Hydroxydopamine (6-OHDA), a neurotoxin that causes the death of dopamine (DA) neurons, is commonly used to produce experimental models of Parkinson's disease (PD) in rodents. In the rat model of PD first described by Sauer and Oertel, DA neurons progressively die over several weeks following a striatal injection of 6-OHDA. It is generally assumed that DA neurons die through apoptosis after exposure to 6-OHDA, but data supporting activation of a caspase enzymatic cascade are lacking. In this study, we sought to determine if caspases involved in the intrinsic apoptotic cascade play a role in the initial stages of 6-OHDA-induced death of DA neurons in the progressively lesioned rat model of PD. We found that injection of 6-OHDA into adult rat striatum did not activate caspase-9 or caspase-3 or increase levels of caspase-dependent cleavage products in the substantia nigra at various survival times up to 7 days after the lesion, even though this paradigm produced DA neuronal loss. These data suggest that in the adult rat brain DA neurons whose terminals are challenged with 6-OHDA do not die through a classical caspase-dependent apoptotic mechanism.

Original languageEnglish
Pages (from-to)317-325
Number of pages9
JournalJournal of Neuroscience Research
Volume86
Issue number2
DOIs
StatePublished - 1 Feb 2008

Keywords

  • Apoptosis
  • Neuronal death
  • Poly(ADP-ribose) polymerase (PARP)
  • Substantia nigra
  • Tau

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