Effects of combination antiretroviral drugs (cART) on hippocampal neuroplasticity in female mice.

The incidence of HIV-associated neurocognitive disorder (HAND) continues despite the introduction of combination antiretroviral drugs (cART). Several studies have reported the neurotoxicity of individual antiretroviral drugs (monotherapy), while the common approach for HIV treatment is through cART. Hence, the current study investigated the effects of long-term exposure to cART on cognitive function, oxidative damage, autophagy, and neuroplasticity in the hippocampus of mice. Female Balb/c mice received a once-a-day oral dose of cART composed of emtricitabine + tenofovir disoproxil fumarate or vehicle for 8 weeks. On week 7 of drug administration, all mice were assessed for spatial learning in the Morris water maze (MWM), and then on week 8, mice were sacrificed, and hippocampal tissue dissected from the brain. For biochemical analyses, we measured the concentration of 4-hydroxynonenal, and the expression of autophagic marker LC3B, synaptophysin, and brain-derived neurotrophic factor (BDNF) in the hippocampus. Our results showed that cART exposure increased escape latency in the MWM test. The cART-treated mice also showed increased 4-hydroxynonenal concentration and expression of LC3B. Furthermore, cART treatment decreased the expression of synaptophysin and BDNF. These findings further support the evidence that cART may be neurotoxic and therefore may play a role in the neuropathogenesis of HAND.