NDLI: D1/NMDA Receptors and Concurrent Methamphetamine+HIV-1 Tat Neurotoxicity

Content Provider	Springer Nature Link
Author	Aksev, Michael Y. Akseva, M. V. Mactutus, C. F. Booze, Rosemarie M.
Copyright Year	2012
Abstract	The interactive effects of HIV-1 infection and methamphetamine (METH) abuse in producing cognitive dysfunction represent a serious medical problem; however, the neural mechanisms underlying this interactive neurotoxicity remain elusive. In this study, we report that a combination of low, sub-toxic doses of METH + HIV-1 Tat 1–86 B, but not METH + HIV-1 gp120, directly induces death of rodent midbrain neurons in vitro. The effects of D1- and NMDA-receptor specific antagonists (SCH23390 and MK-801, respectively) on the neurotoxicity of different doses of METH or HIV-1 Tat alone and on the METH + HIV-1Tat interaction in midbrain neuronal cultures suggest that the induction of the cell death cascade by METH and Tat requires both dopaminergic (D1) and N-methyl D-aspartate (NMDA) receptor-mediated signaling. This interactive METH+Tat neurotoxicity does not occur in cultures of hippocampal neurons, which are predominately glutamatergic, express very low levels of dopamine receptors, and have no functional dopamine transporter (DAT). Thus, the presence of a subpopulation of neurons capable of dopamine release/uptake is essential for METH+Tat induction of the cell death cascade. Overall, our results support the hypothesis that METH and HIV-1 Tat disrupt the normal conjunction of signaling between D1 and NMDA receptors, resulting in neural dysfunction and death.
Starting Page	599
Ending Page	608
Page Count	10
File Format	PDF
ISSN	15571890
Journal	Journal of Neuroimmune Pharmacology
Volume Number	7
Issue Number	3
e-ISSN	15571904
Language	English
Publisher	Springer US
Publisher Date	2012-05-03
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Cell culture HIV-1 Tat HIV-1 gp120 SCH23390 MK-801 Immunology Pharmacology/Toxicology Neurosciences Virology Cell Biology
Content Type	Text
Resource Type	Article
Subject	Neuroscience Immunology and Allergy Pharmacology Immunology

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