Progressive degeneration of dopamine neurons in 6-hydroxydopamine rat model of Parkinson's disease does not involve activation of caspase-9 and caspase-3. J Neurosci Res 2008 Feb 01;86(2):317-25
Date
09/06/2007Pubmed ID
17787016DOI
10.1002/jnr.21480Scopus ID
2-s2.0-38849087433 (requires institutional sign-in at Scopus site) 17 CitationsAbstract
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.
Author List
Ebert AD, Hann HJ, Bohn MCAuthor
Allison D. Ebert PhD Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adrenergic AgentsAnimals
Apoptosis
Brain
Caspase 3
Caspase 9
Caspases
Dopamine
Enzyme Activation
Immunohistochemistry
Male
Nerve Degeneration
Neurons
Oxidopamine
Parkinsonian Disorders
Rats
Rats, Inbred F344
