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Cortical Neurons Exposed to HIV‐1 Nef Exhibit Increased MAP2 Levels
Author(s) -
VargasZapata Valerie,
MartínezOrengo Neysha,
Noel Richard J.
Publication year - 2016
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.30.1_supplement.1179.1
Subject(s) - synaptophysin , neuroinflammation , biology , dendritic spine , astrocyte , neurotoxicity , neuron , neuroscience , microbiology and biotechnology , inflammation , immunology , immunohistochemistry , medicine , central nervous system , hippocampal formation , toxicity
Background Approximately 50% of HIV‐1 patients suffer from neuropathologies despite the success of anti‐retroviral therapy. The HIV viral protein Nef has been found in post mortem brain tissues of HIV‐1 patients with neurocognitive disorders. Studies have demonstrated that Nef is present in the brain even in the absence of viral replication raising the possibility for ongoing neurotoxicity at undetectable viral loads. Our work showed that rats suffer from learning impairments and neuronal loss when infused with astrocytes expressing Nef. This also correlates with an increased expression of inflammatory cytokines that promote neuroinflammation, but this mechanism is not well understood. We hypothesize that neurons undergo morphological changes in response to Nef‐induced inflammation. We tested the effects of Nef on neuron/dendritic marker MAP2 and the synaptic marker synaptophysin in cortical neurons derived from rats. Methods Cortical neurons were co‐cultured with astrocytes expressing Nef or GFP for 48 and 72 hours. Astrocyte lysates were collected for protein quantification and the supernatants for testing pro‐inflammatory markers. Neurons were stained for MAP2 and synaptophysin using immunoflourescense microscopy. Results Qualitative comparison of cortical neurons exposed to Nef show higher expression of MAP2 when compared to GFP control, most noticeable at 72 hours. Synaptophysin expression was stronger at 72 hours for both Nef and GFP exposed cells. Conclusions This preliminary data suggests that Nef increases MAP2 levels in cortical neurons in a time dependent manner. It is of our interest to investigate if the increments we are observing in MAP2 and synaptophysin expression are related to neurogenesis in response to inflammation or a mechanism of Nef leading to cell proliferation. Future directions Further studies will let us better understand the co‐localization and functional effects of MAP2 and synaptophysin in neurons exposed to Nef. Inflammatory markers will be used to study the correlation between Nef, inflammation, and neuronal morphologic changes. Experiments will also be performed in human cell lines and eventually in our in vivo model. Support or Funding Information MBRS‐RISE Program (R25GM082406), Dr. Noel's Lab (GM106970), PHSU‐PRI MAGIC Laboratory (MD007579)