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
PubMed

Insights

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.