James P. Keblesh, Benjamin C. Reiner, Jianuo Liu and Huangui Xiong

Neurophysiology laboratory, the Center for Neurovirology and Neurodegenerative Disorders, and Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5880, U.S.A.

Abstract

HIV-1-associated dementia (HAD) describes the cognitive impairments and behavioral disturbances which afflict many HIV-infected individuals. Although the incidence of HAD has decreased significantly in the era of HAART, it remains a significant complication of HIV-1 infection as patients with acquired immune deficient syndrome (AIDS) live longer, antiretroviral drugs remain unable to effectively cross the blood-brain barrier (BBB), and HIV-1 resistance grows due to viral strain mutation. Although the precise mechanism leading to HAD is incompletely understood, it is commonly accepted its progression involves a critical mass of infected and activated mononuclear phagocytes (MP; brain perivascular macro- phages and microglia) releasing immune and viral products in brain. These cellular and viral products induce neuronal dysfunction and injury via various signaling pathways. Emerging evidence indicates that voltage-gated potassium (K_v) channels, key regulators of cell excitability and animal behavior (learning and memory), are involved in the pathogenesis of HAD/HAND. Here we survey the literature and find HAD related alterations in cellular and viral products can alter MP and neuronal K_v channel activity, leading to MP and neuronal dysfunction and cognitive deficits. Thus, MP and neuronal K_v channels may be a new target in the effort to develop therapies for HAD and perhaps other inflammatory neurodegenerative disorders.