Neuroscience 2005 Abstract
| Presentation Number: | 424.10 |
|---|---|
| Abstract Title: | 6-Hydroxydopamine causes an acute increase in cFos and MAP kinases in the rat striatum. |
| Authors: |
Fischer, M. L.*1
; Leak, R. K.1
; Zigmond, M. J.1
; Smith, A. D.1
1Neurology, Univ. of Pittsburgh, Pittsburgh, PA |
| Primary Theme and Topics |
Disorders of the Nervous System - Neurodegenerative and Movement Disorders -- Parkinson's disease: Therapies |
| Secondary Theme and Topics | Disorders of the Nervous System<br />- Neurotoxicity, Inflammation, and Neuroprotection<br />-- Cell death mechanisms |
| Session: |
424. Parkinson's Disease Models: 6-OHDA Poster |
| Presentation Time: | Monday, November 14, 2005 9:00 AM-10:00 AM |
| Location: | Washington Convention Center - Hall A-C, Board # MM16 |
| Keywords: | Parkinson's Disease, Extracellular Signal Regulated Kinase, cJun-N-terminal Kinase, Dopamine |
We have previously observed using Western blot analysis that the administration of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle causes an increase in the active forms of the MAP kinases (MAPK), ERK1/2 (pERK) and JNK1/2 (pJNK) (Smith et al., SFN, 2004). In this report we describe the effects of 6-OHDA on MAP kinases in the target region of the dopamine (DA) neurons, the dorsal striatum. Adult, male Sprague-Dawley rats received 6-OHDA (6 µg in 1 µl) into the striatum. After 15 min, 30 min, 1 hr, or 3 hr, animals were perfused with 4% paraformaldehyde containing phosphatase inhibitors. Striatal and substantia nigral blocks were then sectioned and stained for pERK and pJNK. By 15 min we observed an increase in pERK that persisted for at least 3 hr. A similar temporal profile was observed for pJNK, although the peak increase was lower than for pERK. The morphology of the cells containing the increased activated MAP kinases suggests that they were medium spiny neurons, although this has not yet been confirmed by double labeling. These changes were accompanied by a delayed increase in cfos, which was first detectable at 1 hr and remained for at least 3 hr. No changes in activated MAP kinases or cfos were observed in the substantia nigra at the timepoints examined. Activation of ERK1/2 and cfos induction has previously been reported following administration of drugs that activate DA receptors, and the induction of cfos can be attenuated by the administration of a DA antagonist. Thus, we hypothesize that changes in activated MAP kinases and in cfos represent the effects of endogenous DA being released in response to the neurotoxic actions of 6-OHDA. This suggests that initial changes in striatal pERK and cfos would be useful as short-term indices of the efficacy of neuroprotective treatments. Experiments are currently underway to test this hypothesis. (Supported by NS19608 and DAMD17-03-1-0479.)µµ.
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2005 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2005. Online.
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