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The alpha7-nicotinic receptor contributes to gp120-induced neurotoxicity: implications in HIV-associated neurocognitive disorders.
Capó-Vélez, Coral M; Morales-Vargas, Bryan; García-González, Aurian; Grajales-Reyes, José G; Delgado-Vélez, Manuel; Madera, Bismark; Báez-Pagán, Carlos A; Quesada, Orestes; Lasalde-Dominicci, José A.
Afiliação
  • Capó-Vélez CM; University of Puerto Rico, Río Piedras Campus, Department of Biology, San Juan, P.R, 00931-3360, Puerto Rico.
  • Morales-Vargas B; University of Puerto Rico, Molecular Sciences and Research Center, San Juan, P.R, 00926, Puerto Rico.
  • García-González A; University of Puerto Rico, Río Piedras Campus, Department of Biology, San Juan, P.R, 00931-3360, Puerto Rico.
  • Grajales-Reyes JG; University of Puerto Rico, Río Piedras Campus, Department of Biology, San Juan, P.R, 00931-3360, Puerto Rico.
  • Delgado-Vélez M; University of Puerto Rico, Río Piedras Campus, Department of Biology, San Juan, P.R, 00931-3360, Puerto Rico.
  • Madera B; University of Puerto Rico, Río Piedras Campus, Department of Biology, San Juan, P.R, 00931-3360, Puerto Rico.
  • Báez-Pagán CA; University of Puerto Rico, Molecular Sciences and Research Center, San Juan, P.R, 00926, Puerto Rico.
  • Quesada O; University of Puerto Rico, Río Piedras Campus, Department of Biology, San Juan, P.R, 00931-3360, Puerto Rico.
  • Lasalde-Dominicci JA; University of Puerto Rico, Molecular Sciences and Research Center, San Juan, P.R, 00926, Puerto Rico.
Sci Rep ; 8(1): 1829, 2018 01 29.
Article em En | MEDLINE | ID: mdl-29379089
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteína gp120 do Envelope de HIV / Infecções por HIV / HIV-1 / Transtornos Neurocognitivos / Síndromes Neurotóxicas / Receptor Nicotínico de Acetilcolina alfa7 / Neurônios Tipo de estudo: Risk_factors_studies Limite: Animals Idioma: En Revista: Sci Rep Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Porto Rico País de publicação: Reino Unido
Texto completo
Adicionar na Minha BVS
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteína gp120 do Envelope de HIV / Infecções por HIV / HIV-1 / Transtornos Neurocognitivos / Síndromes Neurotóxicas / Receptor Nicotínico de Acetilcolina alfa7 / Neurônios Tipo de estudo: Risk_factors_studies Limite: Animals Idioma: En Revista: Sci Rep Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Porto Rico País de publicação: Reino Unido