Background: CXCR4, an important co-receptor for HIV-1 infection, also plays an essential role in neuronal development. Neural progenitor cells (NPCs) have been shown to proliferate or differentiate into neurons or glia and may play important role in neuronal repair after damage by trauma or neuro-generative disorders, such as HIV-1 associated dementia (HAD). Within the brain, mononuclear phagocytes (MP, macrophages, and microglia) and astrocytes help to maintain homeostasis and could be initiators or mediators of this repair process. MP are also the primary population of HIV-1 infected cells in the brain and produce viral proteins such as gp120.

Methods: To examine the role of CXCR4 on NPC function and the possibility that HIV-1 and CXCR4 interactions may affect the neuronal repair process in HAD, we determined CXCR4 expression, signaling, and function on cultured NPCs from rat cortex.

Results: Using immunocytochemistry staining and receptor-ligand binding techniques, we found that CXCR4 was expressed in abundance on NPCs. Importantly, SDF1-a, the ligand for CXCR4, has been shown to be upregulated in astrocytes and neurons exposed to HIV-1 infected MP secretions. CXCR4 was also found to be functional on NPCs by measuring changes in SDF1-a mediated intracellular signaling. This included changes in IP3 formation and cAMP production. T140, a CXCR4 antagonist, and PTX, an inactivator of G-protein coupled receptors, could block these changes. Finally we discovered that SDF1-a and gp120 could inhibit bFGF mediated NPC proliferation.

Conclusions: This suggests that during HAD the production of viral proteins, such as gp120, from MP and the observed increase in SDF1-a production from astrocytes/neurons could influence the process of neural network repair through neural progenitor cells.