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The Role of gp‐120‐Induced Up‐Regulation of the α7 Nicotinic Acetylcholine Receptor in HIV‐Associated Dementia
Author(s) -
Ramos Felix M,
Ballester Leomar,
Santiago Laura,
García Wilfredo,
Acevedo Lauren,
Ríos Raymond,
Mercado Jose,
Capó Coral,
Lasalde Jose
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.lb412
Subject(s) - nicotinic agonist , neurocognitive , acetylcholine receptor , neuroscience , neuroinflammation , human immunodeficiency virus (hiv) , receptor , biology , medicine , immunology , cognition , biochemistry , inflammation
Over 30 million people are infected with HIV worldwide. Approximately 30% of HIV+ patients develop HIV associated neurocognitive disorder (HAND), which is characterized by cognitive impairment, motor dysfunction and behavioral changes. HIV does not directly infect neurons and the molecular mechanisms by which infection leads to neurocognitive decline are not understood. Several hypotheses have emerged to explain the development of HAND in HIV+ individuals, including neuroinflammation mediated by microglia and direct neuronal toxicity by soluble HIV proteins. We focused our studies on the HIV protein gp120. HIV‐gp120 interacts with several membrane receptors including CD4, CCR5, CXCR4 and nicotinic receptors (nAChRs). However, the role that nAChRs play in the development of HAND has not been investigated. We studied how gp120 affects the expression and function of α7‐nAChR in neuroblastoma cells (SH‐SY5Y). Electrophysiology, imaging and qRT‐PCR experiments were conducted on cells exposed to gp120. We found an increase in the levels and function of α7‐nAChRs after treatment with gp120. In addition, qRT‐PCR experiments with HAND+ and HAND‐ samples showed that levels of α7‐nAChRs are higher in basal ganglia in a subset of HAND+ samples. Our data suggest that α7‐nAChRs may play an important role in the development of HAND.