The alpha7-nicotinic receptor contributes to gp120-induced neurotoxicity: implications in HIV-associated neurocognitive disorders
| Autor: | Bryan Morales-Vargas, Manuel Delgado-Vélez, Coral M. Capó-Vélez, Jose G. Grajales-Reyes, José A. Lasalde-Dominicci, Carlos A. Báez-Pagán, Aurian Garcia-Gonzalez, Bismark Madera, Orestes Quesada |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Neurotoxicity Syndrome alpha7 Nicotinic Acetylcholine Receptor Neurocognitive Disorders lcsh:Medicine HIV Infections Mice Transgenic Striatum HIV Envelope Protein gp120 Receptors Nicotinic Hippocampus Calcium in biology Article 03 medical and health sciences Mice 0302 clinical medicine Downregulation and upregulation medicine Animals Receptor lcsh:Science Acetylcholine receptor Neurons Multidisciplinary Cell Death business.industry lcsh:R Neurotoxicity medicine.disease Corpus Striatum 3. Good health Mice Inbred C57BL 030104 developmental biology Nicotinic agonist nervous system HIV-1 lcsh:Q Female Neurotoxicity Syndromes sense organs business Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Scientific Reports Scientific Reports, Vol 8, Iss 1, Pp 1-11 (2018) |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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