7-Chlorokynurenate Ameliorates Neuronal Injury Mediated by HIV Envelope Protein gp120 in Rodent Retinal Cultures.
Prior studies with in vitro model systems have suggested that at least part of the neurological manifestations of AIDS may stem from neuronal injury involving the HIV-1 coat protein gp120. This form of neuronal damage is most probably mediated indirectly by a complex set of cellular interactions among macrophages, astrocytes, and neurons, resulting in a final common pathway of overstimulation of N-methyl-d-aspartate (NMDA) receptors. We studied the neuroprotective effect from gp120-induced neuronal injury of an antagonist of the glycine site of the NMDA receptor, 7-chlorokynurenate. In identified rat retinal ganglion cells in culture, we found that 50 microM 7-chlorokynurenate significantly abrogated the injury engendered by 20 pM gp120. Addition of 300 microM exogenous glycine prevented this protective effect of 50 microM 7-chlorokynurenate. These data suggest that glycine site antagonists of the NMDA receptor may have therapeutic potential for ameliorating neuronal damage associated with gp120.
Lipton
Stuart A.
SA
Laboratory of Cellular & Molecular Neuroscience, Children's Hospital, and the Departments of Neurology, Children's Hospital, Beth Israel Hospital, Brigham & Women's Hospital, and Massachusetts General Hospital; Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA.