| Human immunodeficiency virus (HIV) causes neurological disease in a majority of infected persons, resulting in minor cognitive and motor disorders which begin early in infection. The feline immunodeficiency virus (FIV) model of HIV infection recapitulates the progression of immune system destruction and clinical and subclinical neurological abnormalities. In this study, we examined virological, neuropathological, and neurochemical parameters of cats infected at 3 days and 2 months of age.; Cerebral subcortical white matter volume was reduced 23% (n = 6) compared to age-matched controls (n = 6) in cats infected as neonates and killed 3 months post inoculation (PI), but was normal in cats 6 months PI (n = 6 infected, n = 6 controls). Caudate nucleus volume was reduced 19% in cats infected as juveniles and killed 6 (n = 6) and 24 (n = 6) months PI compared to 6 month old controls (n = 6). Cerebral neocortical gray matter volume was decreased 14% (n = 6) in cats infected as juveniles and killed 24 months PI compared to 6 month old controls (n = 6).; Neurochemical analysis of the caudate nucleus of cats infected as neonates revealed increased dopamine content at 3 and 18 months PI (222 +/- 27 pmol/mg protein, n = 6; 1785 +/- 281 pmol/mg protein, n = 4; respectively) compared against uninfected age matched controls (46 +/- 10 pmol/mg protein, n = 8; 422 +/- 64 pmol/mg protein, n = 7; respectively). Tyrosine hydroxylase immunoreactivity was increased 6 and 18 months PI (215 +/- 19% of control, n = 5 infected, n = 6 controls; and 163 +/- 16% of control, n = 6 infected, n = 6 controls; respectively).; In summary, low brain viral and proviral loads did not correlate with electrodiagnostic abnormalities, suggesting host responses to infection perpetuate functional disturbances. Cerebral neocortical gray matter atrophy without neuronal loss might be due to cell shrinkage, dendritic simplification, or filial cell loss, all of which might be reversible. Neurochemical abnormalities implicate altered dopamine synthesis and turnover in the caudate nucleus during FIV infection. Reductions in GLT1 mRNA in the caudate nucleus and reductions in glutamine synthetase activity in the frontal cortex both suggest astrocytic injury occurs during FIV infection of the feline central nervous system. (Abstract shortened by UMI.)... |
