Role of microglia in methamphetamine-induced neurotoxicity

Abstract

Methamphetamine (Meth) is an addictive psychostimulant widely abused around the world. The chronic use of Meth produces neurotoxicity featured by dopaminergic terminal damage and microgliosis, resulting in serious neurological and behavioral consequences. Ample evidence indicate that Meth causes microglial activation and resultant secretion of pro-inflammatory molecules leading to neural injury. However, the mechanisms underlying Meth-induced microglial activation remain to be determined. In this review, we attempt to address the effects of Meth on human immunodeficiency virus (HIV)-associated microglia activation both in vitro and in-vivo. Meth abuse not only increases HIV transmission but also exacerbates progression of HIV-associated neurocognitive disorders (HAND) through activation of microglia. In addition, the therapeutic potential of anti-inflammatory drugs on ameliorating Meth-induced microglia activation and resultant neuronal injury is discussed.

Keywords: Drug abuse; methamphetamine; microglia; neuroinflammation; neurotoxicity.

Figure 1

Schematic diagrams illustrating the roles played by microglia in health and disease (Meth abuse) conditions. In health, microglia activation is restricted by neuronal immunosuppressive signals. In turn, the microglia secretes neurotrophic factors to support the neuronal function. In Meth abuse condition (disease), however, Meth causes neuronal cell damage, especially the dopaminergic neuronal terminals. The damaged neurons release danger-associated signals leading to microglia activation. The activated microglia produces proinflammatory substances (neurotoxins), exacerbating Meth-associated neurotoxic activity. Thus, inhibition of microglia activation and resultant production of proinflammatory substances could be an important strategy for therapeutic intervention.