Synaptic Plasticity and Neurological Disorders in Neurotropic Viral Infections

Figure 3

A model of HIV-induced neurotoxicity. Infected microglia or macrophages release viral proteins, chemokines, and cytokines. This activates uninfected microglia and macrophages. Neuronal injury, synapse damage, and cell death occur because immune activated and HIV-infected brain microglia and macrophages release neurotoxic elements. Excessive influx of Ca²⁺ ions occurs because of the overactivation of NMDA receptor-coupled ion channels that mediate neuronal injury. As a consequence, potentially harmful enzymes, release of glutamate, and free-radical formation are triggered. Subsequently, glutamate overstimulates NMDA receptors on nearby neurons, which causes additional injury. Upregulation of HDAC2 expression and increased eIF2α-phosphorylation leads to the dysregulated synaptic plasticity gene and protein expression which results in impaired synaptic plasticity.