| First Author | Capó-Vélez CM | Year | 2018 |
| Journal | Sci Rep | Volume | 8 |
| Issue | 1 | Pages | 1829 |
| PubMed ID | 29379089 | Mgi Jnum | J:265792 |
| Mgi Id | MGI:6148664 | Doi | 10.1038/s41598-018-20271-x |
| Citation | Capo-Velez CM, et al. (2018) The alpha7-nicotinic receptor contributes to gp120-induced neurotoxicity: implications in HIV-associated neurocognitive disorders. Sci Rep 8(1):1829 |
| abstractText | Currently, there are no specific therapies to treat HIV-1 associated neurocognitive disorders (HAND). The HIV-1 envelope, gp120, induces neuropathological changes similar to those in HAND patients; furthermore, it triggers an upregulation of the alpha7-nicotinic acetylcholine receptor (alpha7-nAChR), facilitating intracellular calcium overload and neuronal cell death. Using a gp120IIIB-transgenic mouse (gp120-tgm) model, we demonstrate that alpha7-nAChRs are upregulated on striatal neurons. Activation of alpha7-nAChRs leads to an increase in both intracellular calcium and percentage of apoptotic cells, which can be abrogated by antagonizing the receptor, suggesting a role for alpha7-nAChRs in gp120-induced neurotoxicity. Moreover, we demonstrate for the first time that gp120-tgm have learning deficiencies on a striatum-dependent behavioral task. They also show locomotor deficiencies, which improved with alpha7-nAChR antagonists, further supporting a role for this receptor in gp120-induced neurotoxicity. Together, these results uncover a new mechanism through which gp120-induced modulation of alpha7-nAChRs in the striatum can contribute to HAND development. |
