Abstract
Glutamate (Glu) is the most abundant excitatory neurotransmitter in the central nervous system (CNS). HIV-1 and viral proteins compromise glutamate synaptic transmission, resulting in poor cell-to-cell signaling and bystander toxicity. In this study, we identified that myeloid HIV-1-brain reservoirs survive in Glu and glutamine (Gln) as a major source of energy. Thus, we found a link between synaptic compromise, metabolomics of viral reservoirs, and viral persistence. In the current manuscript we will discuss all these interactions and the potential to achieve eradication and cure using this unique metabolic profile.
Highlights
Neurons are not able to perform de novo synthesis of the neurotransmitters glutamate (Glu) and gamma-aminobutyric acid (GABA) from glucose due to the lack of enzymes involved in their metabolism
A multicellular metabolic pathway known as the Glu/GABA-glutamine (Gln) cycle maintains the balance among these metabolites to support neuronal synaptic transmission (Bak et al, 2006)
The pathogenesis of NeuroHIV involves the early (7–10 days post-injection) transmigration of leukocytes carrying the virus across the blood-brain barrier (BBB) using chemokine gradients only sensed by HIV-1-infected monocytes due to their enhanced expression of key chemokine receptors such as CCR2 (Eugenin et al, 2006; Williams et al, 2013)
Summary
Neurons are not able to perform de novo synthesis of the neurotransmitters glutamate (Glu) and gamma-aminobutyric acid (GABA) from glucose due to the lack of enzymes involved in their metabolism. A balance between these two neurotransmitters plays a critical role in several brain functions including learning and memory, development, pain, synaptogenesis, motor stimuli, and synaptic signaling (Petroff, 2002; Allen et al, 2004; Bak et al, 2006; Bonansco and Fuenzalida, 2016; Ford et al, 2017). Alterations in this balance have been associated with brain damage and several neurodegenerative diseases including Alzheimer’s, Parkinson’s, and NeuroHIV.
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