Modeling HIV-1-Associated Neurocognitive Disorders and the Therapeutic Effects of the Phytoestrogen Metabolite S-Equol in the HIV-1 Transgenic Rat
Date of Award
Open Access Dissertation
Charles F. Mactutus
HIV-1 associated neurocognitive disorders (HAND) continue to afflict individuals with HIV-1 in the combination antiretroviral treatment (cART) era, most notably affecting executive function, as well as preattentive processing. Currently, there is no effective treatment for HAND, with only adjunctive treatment targeting symptomatic relief. There were two hypotheses in this dissertation: 1) that HIV-1 Tg rats will show disruptions in measures of executive function and preattentive processing, as well as neural network alterations in the prefrontal cortex (PFC), a brain region implicated in executive function, and 2) that administration of the phytoestrogen metabolite S-equol will improve performance as measured by executive function and attention, as well as neuronal network complexity in the PFC. In experiment 1, using prepulse inhibition of the auditory startle response and a series of operant tasks, deficits were revealed in perceptual sharpening, sustained attention, and core components of executive function. Daily oral S-equol treatments (0, 0.05, 0.1, and 0.2 mg), administered to the animals at 6-8 months of age, improved the performance of the HIV-1 Tg animals on the sustained attention task. Assessment of neuronal networks with diOlistic labeling of pyramidal neurons in the PFC suggested that the 0.2 mg dose of S-equol ameliorated alterations in the HIV-1 Tg animals as well.
In experiment 2, treatment with S-equol (0.2 mg), begun at 2-3 months of age, significantly delayed or prevented deficits in sustained attention. HIV-1 Tg animals that received S-equol also displayed enduring improvements in performance one month after the treatment ended, an effect not detected in any of the other groups. However, further assessments of increased demands on sustained attention as well as selective attention did not further differentiate the HIV-1 Tg and control animals.
In summary, the HIV-1 Tg rats displayed impaired performance in preattentive processing, attention, and executive function, prior to any clinical signs of wasting. S-equol was effective in both ameliorating and preventing attentional deficits, suggesting its potential use as a therapeutic for neurocognitive impairments in HAND.
Moran, L. M.(2013). Modeling HIV-1-Associated Neurocognitive Disorders and the Therapeutic Effects of the Phytoestrogen Metabolite S-Equol in the HIV-1 Transgenic Rat. (Doctoral dissertation). Retrieved from https://scholarcommons.sc.edu/etd/2467