Infection by the human immunodeficiency virus (HIV) results in neurodegeneration caused by aberrant activation of glial cells with ensuing neuronal death. Since patients with HIV/AIDS often develop opportunistic infections, we studied the role of systemic immune activation on neurological function and viral replication in the brain. For this purpose, we repeatedly administered lipopolysaccharide (LPS), a component of the membrane of gram-negative bacteria, to cats infected with feline immunodeficiency virus (FIV), as an animal model of HIV encephalopathy. After behavioral assessment, animals were sacrificed and proteins and mRNA were extracted from cerebral cortex and basal ganglia, for immunoblotting of neuronal markers and RT-PCR analyses of genes for inflammatory cytokines and neurotrophic factors. FIV-infected cats treated with LPS developed less severe neurobehavioral deficits (mean deficit score 1.4 ± 0.2 in FIV-LPS group versus 3.6 ± 0.2 in FIV group, p < 0.05) and showed lower brain viral load than the FIV-infected control group. Moreover, we observed reduced loss of the presynaptic protein synaptophysin and the vesicular acetylcholine transporter, and up-regulation of the mRNA for brain-derived neurotrophic factor (BDNF) in the basal ganglia, despite high levels of the pro-inflammatory cytokine IL-1beta. Other neurotrophins (IGF-1, GDNF), as well as the mannose receptor, were not affected by LPS treatment. Thus, systemic LPS improved neurological function and synaptic architecture in FIV-infected animals through a mechanism involving increased expression of BDNF and reduced viral replication. Our findings emphasize the beneficial aspects of selective activation of innate immunity in neurological disease.

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