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Sci Rep. 2018 Jan 29;8(1):1829. doi: 10.1038/s41598-018-20271-x.

The alpha7-nicotinic receptor contributes to gp120-induced neurotoxicity: implications in HIV-associated neurocognitive disorders.

Author information

1
University of Puerto Rico, Río Piedras Campus, Department of Biology, San Juan, P.R, 00931-3360, Puerto Rico.
2
University of Puerto Rico, Molecular Sciences and Research Center, San Juan, P.R, 00926, Puerto Rico.
3
University of Puerto Rico, Río Piedras Campus, Department of Physical Sciences, San Juan, P.R, 00931-3360, Puerto Rico.
4
University of Puerto Rico, Río Piedras Campus, Department of Biology, San Juan, P.R, 00931-3360, Puerto Rico. jlasalde@gmail.com.
5
University of Puerto Rico, Río Piedras Campus, Department of Chemistry, San Juan, P.R, 00931-3360, Puerto Rico. jlasalde@gmail.com.
6
University of Puerto Rico, Molecular Sciences and Research Center, San Juan, P.R, 00926, Puerto Rico. jlasalde@gmail.com.

Abstract

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 α7-nicotinic acetylcholine receptor (α7-nAChR), facilitating intracellular calcium overload and neuronal cell death. Using a gp120IIIB-transgenic mouse (gp120-tgm) model, we demonstrate that α7-nAChRs are upregulated on striatal neurons. Activation of α7-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 α7-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 α7-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 α7-nAChRs in the striatum can contribute to HAND development.

PMID:
29379089
PMCID:
PMC5788855
DOI:
10.1038/s41598-018-20271-x
[Indexed for MEDLINE]
Free PMC Article

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