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Methamphetamine augments HIV‐1 Tat mediated memory deficits by altering the expression of synaptic proteins and neutrophic factors
Author(s) -
Nookala Anantha Ram,
Kumar Anil
Publication year - 2017
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.31.1_supplement.662.9
Subject(s) - meth , methamphetamine , neurotoxicity , morris water navigation task , neuroplasticity , genetically modified mouse , neurocognitive , synaptic plasticity , pharmacology , neuroinflammation , elevated plus maze , medicine , psychology , immunology , transgene , biology , hippocampus , neuroscience , disease , toxicity , chemistry , cognition , psychiatry , receptor , monomer , polymer , biochemistry , organic chemistry , acrylate , gene , anxiety
Methamphetamine (METH) abuse is common among individuals infected with HIV‐1 and has been shown to affect disease progression towards AIDS. These HIV‐1 infected individuals also exhibit greater neuronal injury and higher cognitive decline. Several HIV‐1 proteins, specifically gp120 and HIV‐1 Tat have been shown to affect neurocognition. HIV‐1 Tat, a viral protein released early during HIV‐1 replication has been implicated in HIV‐associated neurotoxicity mediated through production of pro‐inflammatory cytokines, reactive oxygen species and dysregulation of neuroplasticity, among many others in the central nervous system. However, combined effect of METH and HIV‐1 Tat on neurocognition and its potential effect on neuroplasticity mechanisms is not well documented. The present study was undertaken to determine the combined effect of METH and HIV‐1 Tat on behavior and neuroplasticity markers. Doxycycline (DOX)‐inducible HIV‐1 Tat (1–86) transgenic mice were administered 6mg/kg MA twice a day. Expression of Tat in various brain regions was confirmed by RT‐PCR. Behavior studies were performed in both males and female mice after 3 weeks of MA administration. We employed Y maze and Morris water maze to determine cognition in these mice. Working memory, indicated by number of spontaneous alterations, was decreased significantly in Tat mice that were administered METH. In the water maze task, there was a significant increase in escape latency in all the groups compared to control mice, and the memory deficit was larger in Tat transgenic mice that were administered MA. There is significant decrease in the protein expression of synapsin1, synaptophysin, arg3.1, PSD95 and BDNF in different brain regions. We also looked at the expression levels of a second marker of synaptodendritic integrity, Calmodulin kinase II (CaMKII) by immunoblotting. The results indicate that CaMKII is significantly decreased in HIV‐1 Tat mice that were treated with METH in both sexes. This study therefore provides novel insights into the interaction of HIV‐1 Tat and METH on the dysregulated expression of various plastic proteins in different brain regions. Support or Funding Information The work was supported by the grants DA025528, DA025011 and AA020806 from National institute of health (NIH).