Bennett BA, Lee GD.
J Neurovirol. 1998 Jun 3-6; 4: 342.
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC.
In both children and adults, HIV-1 infection is commonly associated with neurological manifestations that can include cognitive and motor impairments as well as various organic mental disorders. These CNS disturbances can occur in the absence of opportunistic infections and also in the absence of direct infection of neurons by HIV-1. This neurological impairment caused by HIV-1 has been proposed to involve an alteration of neuronal function by viral particles or cytokines released from infected cells. Our lab, as well as others, have shown that the HV-1 glycoprotein gp120 can elicit neurotoxicity when cultured cells are exposed to even very low concentrations (nanmolar). The precise mechanism by which this occurs is not known, but theories suggest that NMDA receptors (via enhanced intracellular Ca+) as well as nitric oxide may contribute to the neuronal degeneration. We previously showed that gp120 could elicit a neurotoxic response from cultured dopamine neurons after a 24-hour exposure and that this effect could be blocked by NMDA receptor antagonists or nitric oxide synthase inhibitors. Our current findings suggest that a neurotoxic effect can also be elicited from cultured serotonergic neurons. Low concentrations of gp120 (100 pM - 1 nM; 3 days) can induce a series of events which ultimately cause a reduction in the ability of these cells to transport serotonin (20-30% decrease). Serotonin cells, originating in the raphe nucleus, provide a diffuse innervation to various areas of the forebrain, cerebellum, brainstem and spinal cord. Deficits in this neuronal system would have complex effects on the nervous system and could have an impact upon serotonin-mediated behavioral events. These studies are being continued to determine if NMDA receptors and/or nitric oxide production are contributing factors to this gp120-induced neuronal damage.
Publication Types:
Keywords:
- Adult
- Capsid Proteins
- Cells, Cultured
- Central Nervous System
- Child
- HIV Envelope Protein gp120
- HIV Infections
- HIV-1
- Humans
- Neurons
- Neurosciences
- Raphe Nuclei
- Receptors, N-Methyl-D-Aspartate
- Serotonin
- immunology
Other ID:
UI: 102237371
From Meeting Abstracts