Neuroscience 2005 Abstract
| Presentation Number: | 1007.15 |
|---|---|
| Abstract Title: | Methamphetamine preconditions dopaminergic cells to oxidative stress. |
| Authors: |
El Ayadi, A.*1
; Lin, E.1
; Zigmond, M. J.1
1Dept Neurol, Univ. of Pittsburgh, Pittsburgh, PA |
| Primary Theme and Topics |
Disorders of the Nervous System - Neurodegenerative and Movement Disorders -- Parkinson's disease: Other |
| Session: |
1007. Parkinson's Disease III Poster |
| Presentation Time: | Wednesday, November 16, 2005 3:00 PM-4:00 PM |
| Location: | Washington Convention Center - Hall A-C, Board # QQ10 |
| Keywords: | Parkinson's disease, 6-OHDA, MN9D cells, preconditionning |
Exposure to a mild stressor can often precondition cells such that they are less sensitive to a more intense stress of the same or different type. Although most of this work has involved ischemic preconditioning, we have recently shown that preconditioning also can be seen as a result of mild oxidative stress in a cellular model of Parkinson’s disease (see Leak et al., SFN, 2005). In this report, we further extend our observations to include the use of methamphetamine (METH) as a preconditioning stimulus. METH acts by releasing dopamine (DA) from vesicles, inhibiting monoamine oxidase, and reversing high affinity DA transport across cell membranes. For these studies we used the dopaminergic cell line MN9D cultured in the presence of serum, measuring cellular viability with an assay for ATP. We first observed that exposure of MN9D cells to METH (5 mM) for 24 hr caused a large reduction in cellular viability (-89%). Next, MN9D cells were exposed to 6-hydroxydopamine (6-OHDA), a neurotoxin that is accumulated in DA cells and can cause cell death as a result of excessive oxidative stress. Exposure to 6-OHDA (100 µM) alone for 15 min caused a 54% loss of viability as measured 24 hr later. In contrast, when cells were pretreated with a lower concentration of METH (0.5 – 2.0 mM) for 24 hr prior to the 6-OHDA, the toxic effects of 6-OHDA were reduced by 34 to 42%. In an initial attempt to determine the role of endogenous DA in the neurotoxic effects of METH, cells were exposed to reserpine, a drug that depletes cells of DA by inhibiting its storage via the vesicular monoamine transporter. Reserpine (1 µM) decreased basal cell viability by 58%, and increased the toxic effects of 6-OHDA. Reserpine also reduced the protection against 6-OHDA afforded by METH, although it is not yet clear if that was simply a result of the increased toxicity of the 6-OHDA or a reflection of the role of DA in METH-induced preconditioning. Ongoing experiments are exploring further the mechanism underlying methamphetamine induced protection against subsequent insults.
Supported by NS19608 and DAMD17-03-1-0479
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2005 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2005. Online.
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