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Publication Abstract Display
Type: Published Abstract
Title: Long­term effects of Methamphetamine abuse in an in vivo model of HIV­ associated neurocognitive disorders.
Authors: Hoefer MM, Sanchez AB, Maung R, De Rozieresi CM, Dowling CC, Catalan IC, Thaney VE, Pinacrespo J, Zhang D, Robert AJ, Kaul M
Year: 2015
Publication: Society for Neuroscience
Volume: Issue: Pages:
Abstract:Methamphetamine (METH) abuse is very common in HIV­1 positive individuals and is suspected to aggravate HIV­ associated neurocognitive disorders (HAND). HIV­1/gp120 transgenic (gp120tg) mice express a soluble viral envelope in the brain and manifest several neuropathological features similar to those observed in the brains of AIDS patients, including decreased synaptic and dendritic density, as well as astrocytosis and increased numbers of activated microglia. METH is a psychostimulant that compromises several neurotransmitter systems, including the dopaminergic, glutaminergic, and serotonergic networks and it also affects the immune system. So far, the combined effects of HIV­1 and METH are incompletely understood. In this study, gp120tg mice were treated with an escalating METH binge regimen and the chronic effects thereof were analyzed after 5 months when the mice were about 10 months of age. Neuropathology was analyzed using immunofluorescence staining of MAP­2 and synaptophysin in cortex and hippocampus and quantitative deconvolution microscopy. METH treatment induced a significant reduction of MAP­2 and synaptophysin positive neuropil in gp120tg and WT brains. Electrophysiological studies in hippocampal slices revealed that only METH­exposed gp120tg animals displayed reduced post­tetanic potentiation, whereas both gp120 expression and METH treatment lead to reduced long­ term potentiation. To understand the molecular basis of these alterations, we analyzed the expression of components of the GABAergic and glutaminergic neurotransmitter systems at RNA level using a quantitative RT­PCR array. METH and gp120 caused a significant down­regulation of numerous genes involved in both neurotransmission systems. Upon METH treatment, the only upregulated genes were CDK5 and BDNF, known to be involved in learning and synaptic plasticity and METH dependence, respectively. Behavioral tests showed that both gp120tg and WT animals treated with METH had impaired learning and memory. In summary, METH treatment and HIV­1/gp120 expression resulted in pre­ and postsynaptic alterations in association with compromised learning and memory functions.

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