UC Riverside

Antiretroviral therapy (ART) has played a key role in extending the longevity of individuals infected with HIV. Although life expectancy increased significantly, aging with the virus has presented a new study of interest as neurocognitive impairments begin manifestations in individuals living with HIV. These manifestations lead researchers to investigate the involvement of HIV and HIV-associated neurodegeneration (HAND). As interest in this area grows, researchers demonstrate the current pathology of neuro-HIV and the damage manifests in HAND patients. The current neuropathology of HIV neuronal damage demonstrates the initiation of CD4 and chemokine coreceptors, CCR5 and CXCR4 in the brain to activate macrophages and microglia for the release of neurotoxic substances to neurons. The use of ART has provided a decreased incidence of extreme neurological impairments in HIV patients, yet, there were no significant changes to the overall incidence of HAND with ART, producing a gap for treatment against neuro-HIV. Many researchers are currently investigating different targets in neuro-HIV pathogenesis, such as chemokines, cytokines, leukotrienes, etc., to inhibit inflammatory responses that could be used as potential treatments for neuroprotection. Montelukast is a cysteinyl-leukotriene receptor 1 antagonist, initially used as an anti-inflammatory drug for asthma. Cysteinyl leukotrienes have been shown to correlate with the inflammatory response of neuro-HIV, which is why we want to see if the drug will inhibit this response and demonstrate neuroprotection in HIV-infected brains. In this paper, we will investigate the effects of a cysteinyl leukotriene receptor 1 antagonist, Montelukast in HIV gp120 mice We will conduct a 2-month administration of Montelukast and saline to HIV-gp120 transgenic and wild-type mice and then analyze the effects of the Montelukast through immunofluorescence staining and statistical analysis. Our findings suggest the neuroprotective effects of Montelukast on MAP-2-positive neuronal dendrites, presynaptic synaptophysin-positive terminals, and Iba-1-positive microglia in the cortex. Iba-1 also demonstrated a significant decrease of microglia in the hippocampus, an indication of neuroprotection in the brain. However, no other significant changes indicating neuroprotection were observed in HIV-gp120 transgenic mice treated with Montelukast.