Human immunodeficiency virus type 1 (HIV-1) invades the central nervous system (CNS) shortly after infection and becomes localized in varying concentrations in different brain regions, the most vulnerable is the basal ganglia (BG). It is hypothesized that HIV-1-mediated neuropathogenesis involves degeneration of dopaminergic neurons in the substantia nigra and the loss of dopaminergic terminals in the BG, leading to deficits in the central dopaminergic activity, resulting in progressive impairment of neurocognitive and motor functions. In the era of highly active antiretroviral therapy (HAART), although the incidence of HIV-associated dementia (HAD) has decreased, the neurocognitive and neuropsychological deficits continue to persist after HAART. In this study, We investigated the impact of HIV-1 on dopaminergic activity with respect to concentrations of dopamine (DA) and homovanillic acid (HVA) in different regions of postmortem human brains of HIV-1-negative and HIV-1+ individuals and their relationship to neurocognitive impairment. We found that in HIV-1+ as well as HIV-negative cases, dopamine and HVA concentrations in ranged widely in different brain regions. In HIV-negative brain regions, the highest concentration of DA was found in putamen, caudate, substantia nigra, and the basal ganglia. In HIV-1+ cases, there was a significant decrease in DA levels in caudate nucleus, putamen, globus pallidus, and substantia nigra compared to that in HIV-negative cases. In HIV-1+ cases, a strong correlation was found between DA levels in substantia nigra and other brain regions. Concentration of HVA in HIV-negative cases was also highest in the regions containing high dopamine levels. However, no significant decrease in regional HVA levels was found in HIV-1+ cases. HIV-1 RNA load (nondetectable [ND] to log10 6.9 copies/g tissue) also ranged widely in the same brain regions of HIV-1+ cases. Interestingly, the brain regions having the highest HIV-1 RNA had the maximum decrease in DA levels. Age, gender, ethnicity, and postmortem interval were not correlated with decrease in DA levels. Profile of DA, HVA, and HIV-1 RNA levels in the brain regions of HIV-1+ individuals treated with HAART was similar to those not treated with HAART. A majority of HIV-1+ individuals had variable degrees of neurocognitive impairments, but no specific relationship was found between the regional DA content and severity of neurocognitive deficits. These findings suggest widespread deficits in dopamine in different brain regions of HIV-1-infected cases, and that these deficits may be the results of HIV-1-induced neurodegeneration in the subcortical regions of human brain.

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This study suggests that Cetrorelix reduces various inflammatory cytokines and growth factors in rat prostate and, at doses which do not induce castration levels of testosterone, can lower prostate weights. Our findings shed light on the mechanism of action of LHRH antagonists in BPH.

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The effects of a 10-week group-based cognitive-behavioral stress management (CBSM) intervention on psychological distress and plasma free testosterone in symptomatic, HIV-seropositive men were examined. Participants were randomized to either CBSM (n = 42) or a wait-list control group (n = 23). Men in the CBSM intervention showed significant increases in testosterone, whereas control participants showed significant decreases. Those participating in CBSM had significant distress reductions, whereas controls showed no such change. Alterations in free testosterone were inversely related to changes in distress states over time, independent of any changes in cortisol. These findings demonstrate that a short-term CBSM intervention increases free testosterone levels among symptomatic, HIV-seropositive men, and alterations in free testosterone are associated with changes in psychological distress observed during CBSM.

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Reduced level of serotonin (5-hydroxytryptamine, 5-HT) in humans has been associated with a number of mental health and behavioral problems including depression, aggression, violence, sexual dysfunctions, sleep and eating disorders. Even though among HIV-1-infected individuals, prevalence of mental health and behavioral problems are common, their relationship with central nervous system serotonin functions is not clearly understood. This investigation was carried out to study the status of CSF 5-HT in HIV-1+ subjects (n = 21), in the early stage of infection, and HIV-1– control subjects (n = 24). Samples of CSF were obtained by lumbar puncture and were analyzed for 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA), using high-performance liquid chromatography equipped with electrochemical detector. Levels of CSF 5-HT were significantly lower in the HIV-1+ group compared to the HIV-1– group. There was no significant difference in the CSF 5-HIAA levels between the two groups. In both groups, however, there was a significant correlation between CSF 5-HT and 5-HIAA. In the HIV-1 + group, although CSF 5-HT level was significantly negatively correlated with serostatus, there was no correlation between either CSF 5-HT or 5-HIAA levels and CD4 cell number or any behavioral measures evaluated in this study, including Beck’s Depression Inventory and state/trait anxiety scores. These data suggest that HIV-1 infection affects the CNS 5-HT status with no significant association with measures of depression and anxiety, at least in the early stage of infection.

Serotonin has been implicated to play an important role in regulating emotions and behavior, and it is well accepted that the platelet serotonergic system mirrors the presynaptic central serotonergic system. Since prevalence of psychiatric problems increases with age and women are known to be more vulnerable than men, the present investigation was carried out to study the relationship between serotonin activity and age in women. Levels of serotonin (5-hydroxytryptamine, 5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) were measured in platelets and plasma in women (n = 49) aged 40– 84 years (30 women aged 40–60 years and 19 women aged 61–84 years). There was a significant age difference between the two groups (mean: 47.6 ± 5.91 years in the younger and 73.0 ± 6.83 years in the older women, respectively, p < 0.00001). Platelet 5-HT as well as 5-HIAA levels were significantly higher in older women as compared to those in the younger women (89.41 ± 21.95 ng/10⁸ platelets in younger vs. 112.9 ± 36.07 in older women, p < 0.02, and 1.20 ± 1.10 in younger vs. 2.19 ± 1.88 ng/10⁸ platelets in older women, p < 0.05, respectively). Pearson correlation coefficients determined in the combined group (n = 49) showed a significant positive correlation between platelet 5-HT and age (r = 0.31, p < 0.03). Plasma 5-HT levels on the other hand were lower in older women compared to those in the younger women (4.50 ± 3.20 in younger vs. 1.04 ± 1.28 ng/ml plasma in older women, p < 0.0001) and a significant negative correlation was observed between plasma 5-HT and age (r = –0.44, p < 0.002). Plasma 5-HIAA concentration did not differ between the two groups. Platelet 5-HT levels in the younger group were independent of ethnicity. Since high serotonin activity has also been associated with psychiatric problems, our results of increased concentration of platelet 5-HT as well as 5-HIAA with age may have implications in predisposing aging women to behavioral/psychiatric problems.