Potential Effects of Nrf2 in Exercise Intervention of Neurotoxicity Caused by Methamphetamine Oxidative Stress

Figure 1

The important function of oxidative stress in the central nervous system toxicity of METH. METH enters DA energetic neurons by through the plasma membrane and prevents DA reuptake by inhibiting DAT and VMAT2, resulting in increased release of DA and excessive accumulation in the extracellular space (including synaptic clearance). Excessive quinones, ROS, and RNS accumulate in the endings of DA neurons, leading to a surge in oxidative stress levels. Extracellular ROS and RNS diffuse toward MSN neuronal and nonneuronal cells, such as the BBB neurovascular unit, astrocytes, and/or glia. Adverse effects include abnormal activation of D1 receptors; induced release of glutamate neuronal transmitters; activation of NMDA and AMPA receptors; increased intracellular Ca²⁺ concentration; further increased oxidative stress level and protein oxidation; disrupted homeostasis of the endoplasmic reticulum (ER) and mitochondria; impaired intracellular clearance system function; DNA oxidative damage and stability loss; early gene expression activation, increased inflammatory gene expression; damaged astrocytes; activation of microglia; impaired endothelial function of the BBB; increased permeability; and inflammatory factor overflow. Created with http://BioRender.com.