The effect of methamphetamine and amphetamine on the activity of matrix metalloproteinase-2 and 9 in BV2 microglia cells.

Abstract

Methamphetamine (METH) and amphetamine (AMPH) are psychostimulants that are indirect agonists resulting in excess dopamine release within the brain leading to drug-induced neurodegeneration. Microglia cells respond to this neural damage and release matrix metalloproteinase (MMPs) that play an important role in tissue remodeling and potentially a breakdown of the blood brain barrier. Since MMP-2 and 9 enzyme activity can be measured by gelatin zymography, we stimulated a microglia cell line, BV2, exposed to different concentrations of lipopolysaccharide (LPS), to determine the maximum activity of MMP-2 and 9 under stimulatory conditions. This will model microglia exposure to a neurodegenerative environment. The concentration of LPS with the most activity will then be used in conjunction with a dilution series of METH and AMPH. The MMP activity levels from those treated cells will be assessed through gelatin zymographic techniques. Due to tissue damage and BBB remodeling that occurs after abusing psychostimulants, we hypothesize that the activity of MMP-2 and 9 will be up regulated when exposed to METH and AMPH in the presence of LPS stimulation. The upregulation of MMP activity may be linked to the neurodegeneration that occurs in the brain due to misuse of psychostimulants.