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Relationship between methamphetamine exposure and matrix metalloproteinase 9 expression.
Yun Liu1, Sheketta Brown, Jamaluddin Shaikh
1Department of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
Neuroreport
|September 4, 2008
Summary
Matrix metalloproteinase (MMP) 9 is not involved in methamphetamine neurotoxicity. Studies show MMP9 gene expression changes do not correlate with dopamine loss, and knockout mice still experience neurotoxicity.
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- Methamphetamine (MA) abuse leads to significant neurotoxicity, particularly affecting dopamine pathways.
- Matrix metalloproteinase 9 (MMP9) is implicated in various neurological processes, including neuroinflammation and tissue remodeling.
Purpose of the Study:
- To investigate the role of MMP9 in the neurotoxic effects of methamphetamine.
- To determine if MMP9 contributes to methamphetamine-induced dopamine depletion.
Main Methods:
- Administered stimulant and toxic doses of methamphetamine to mice.
- Measured MMP9 gene expression in the brain at various time points.
- Assessed striatal dopamine levels as a marker of neurotoxicity.
- Utilized MMP9 knockout mice to evaluate MA neurotoxicity in the absence of MMP9.
Main Results:
- Methamphetamine rapidly upregulated MMP9 gene expression, with levels returning to baseline in stimulant-treated mice but remaining elevated in toxic dose groups.
- Striatal dopamine reductions, indicative of neurotoxicity, occurred 1-7 days post-exposure but were not associated with concurrent MMP9 expression changes.
- MMP9 knockout mice exhibited normal methamphetamine-induced neurotoxicity, indicating MMP9 is not essential for this process.
Conclusions:
- MMP9 gene expression is upregulated by methamphetamine but does not appear to mediate methamphetamine-induced neurotoxicity.
- The findings suggest MMP9 may play a role in the nervous system's response to methamphetamine, potentially in tissue remodeling rather than direct toxicity.
