Premium
Astrogliosis and downregulation of EAAT2 in rats infused with Nef transfected astrocytes.
Author(s) -
Valles Ortiz Jaydie M.,
Cruz Myrella L.,
Rodriguez Yarelis L.,
Cintron Kevin M.,
Noel Richard J.
Publication year - 2018
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.2018.32.1_supplement.545.18
Subject(s) - astrogliosis , astrocyte , glial fibrillary acidic protein , excitotoxicity , neurotoxicity , morris water navigation task , hippocampus , glutamate receptor , hippocampal formation , dentate gyrus , glutamate aspartate transporter , biology , extracellular , chemistry , microbiology and biotechnology , endocrinology , neuroscience , medicine , central nervous system , biochemistry , toxicity , immunohistochemistry , immunology , excitatory amino acid transporter , receptor
Astrocytes play a major role in homeostasis and neuronal function by preventing excitotoxicity in the CNS. During HIV infection, astrocytes are reported to produce early viral proteins such as Nef, which is known to cause neurotoxicity. Excitatory amino acid transporter 2 (EAAT2) is one of the major astroglial transporters involved in the regulation of extracellular glutamate concentration. We investigated astrocytes transfected with Nef to understand the effect on learning, astrocyte morphology and glutamate transporter expression. Primary rat astrocytes expressing Nef or GFP were infused in the right hippocampus of 30‐day‐old male Sprague Dawley rats. Learning was assessed by Morris water maze five days after infusion. Brain tissues were collected for immunofluorescence staining and the morphological assessment of astrocytes and EAAT2 expression was assessed in different areas of the hippocampus (CA3 and dentate gyrus) using Image J software. In astrocytes, glial fibrillary acidic protein (GFAP) area fraction was significantly increased (P<0.05), while EAAT2 expression was significantly decreased (p<0.05) in the Nef‐treated group when compared to GFP controls. No differences in the length of processes in astrocytes were found, however the number of secondary processes was increased in the Nef‐treated animals. The increase of astrogliosis as measured by GFAP staining, the number of secondary processes, and the decrease of EAAT2 correlates with the learning impairment shown by the Nef‐treated group. These results suggest that there might be an astrocyte dysfunction that affects glutamate uptake at the synaptic cleft leading to neuronal toxicity. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .