Interactive HIV-1 Tat and Morphine-Induced Synaptodendritic Injury Is Triggered through Focal Disruptions in Na+ Influx, Mitochondrial Instability, and Ca2+ Overload

• DOI: 10.1523/jneurosci.5351-13.2014
• Publication Date: 2014-09-17T17:39:00Z
• Authors: S. Fitting; P. E. Knapp; S. Zou; W. D. Marks; M. S. Bowers; H. I. Akbarali; K. F. Hauser
• Keywords: CNQX; Sigma-1 Receptor

Synaptodendritic injury is thought to underlie HIV-associated neurocognitive disorders and contributes exaggerated inflammation cognitive impairment seen in opioid abusers with HIV-1. To examine events triggering combined transactivator of transcription (Tat)- morphine-induced synaptodendritic systematically, striatal neuron imaging studies were conducted <i>in vitro</i>. These demonstrated nearly identical pathologic increases dendritic varicosities as Tat transgenic mice vivo</i>. caused significant focal intracellular sodium ([Na⁺]_i) calcium ([Ca²⁺]_i) dendrites that accompanied by the emergence varicosities. effects largely, but not entirely, attenuated NMDA AMPA receptor antagonists MK-801 CNQX, respectively. Concurrent morphine treatment accelerated Tat-induced varicosities, which localized [Ca²⁺]_i instability mitochondrial inner membrane potential. Importantly, morphine9s prevented μ-opioid antagonist CTAP observed neurons cultured from knock-out mice. Combined Tat- initial losses ion homeostasis ryanodine inhibitor ryanodine, well pyruvate. In summary, induced [Na⁺]_i, instability, excessive Ca²⁺ influx through glutamatergic receptors, swelling along dendrites. Morphine, acting via exacerbates these excitotoxic at same subcellular locations mobilizing additional further disrupting homeostasis. We hypothesize spatiotemporal relationship aberrant AMPA/NMDA glutamate signaling critical defining location degree opiates exacerbate commonly neuroAIDS.