HIV-1, Methamphetamine and astrocyte glutamate regulation

Combined excitotoxic implications for neuro-AIDS

Irma Cisneros, Anuja Ghorpade

Research output: Contribution to journalReview article

39 Citations (Scopus)

Abstract

Glutamate, the most abundant excitatory transmitter in the brain can lead to neurotoxicity when not properly regulated. Excitotoxicity is a direct result of abnormal regulation of glutamate concentrations in the synapse, and is a common neurotoxic mediator associated with neurodegenerative disorders. It is well accepted that methamphetamine (METH), a potent central nervous stimulant with high abuse potential, and human immunodeficiency virus (HIV)-1 are implicated in the progression of neurocognitive malfunction. Both have been shown to induce common neurodegenerative effects such as astrogliosis, compromised blood brain barrier integrity, and excitotoxicity in the brain. Reduced glutamate uptake from neuronal synapses likely leads to the accumulation of glutamate in the extracellular spaces. Astrocytes express the glutamate transporters responsible for majority of the glutamate uptake from the synapse, as well as for vesicular glutamate release. However, the cellular and molecular mechanisms of astrocyte-mediated excitotoxicity in the context of METH and HIV-1 are undefined. Topics reviewed include dysregulation of the glutamate transporters, specifically excitatory amino acid transporter-2, metabotropic glutamate receptor(s) expression and the release of glutamate by vesicular exocytosis. We also discuss glutamate concentration dysregulation through astrocytic expression of enzymes for glutamate synthesis and metabolism. Lastly, we discuss recent evidence of various astrocyte and neuron crosstalk mechanisms implicated in glutamate regulation. Astrocytes play an essential role in the neuropathologies associated with METH/HIV-1-induced excitotoxicity. We hope to shed light on common cellular and molecular pathways astrocytes share in glutamate regulation during drug abuse and HIV-1 infection.

Original languageEnglish (US)
Pages (from-to)392-406
Number of pages15
JournalCurrent HIV Research
Volume10
Issue number5
DOIs
StatePublished - Sep 21 2012
Externally publishedYes

Fingerprint

Methamphetamine
Astrocytes
HIV-1
Glutamic Acid
Acquired Immunodeficiency Syndrome
Synapses
Amino Acid Transport System X-AG
Excitatory Amino Acid Transporter 2
Central Nervous System Stimulants
Metabotropic Glutamate Receptors
Exocytosis
Brain
Extracellular Space
Virus Diseases
Blood-Brain Barrier
Neurodegenerative Diseases
Substance-Related Disorders
Neurons

Keywords

  • Astrocytes
  • EAAT-2
  • Excitotoxicity
  • GFAP
  • Glutamate
  • Human immunodeficiency virus-1
  • Methamphetamine

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology

Cite this

HIV-1, Methamphetamine and astrocyte glutamate regulation : Combined excitotoxic implications for neuro-AIDS. / Cisneros, Irma; Ghorpade, Anuja.

In: Current HIV Research, Vol. 10, No. 5, 21.09.2012, p. 392-406.

Research output: Contribution to journalReview article

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