HIV-1 gp120 enhances giant depolarizing potentials via chemokine receptor CXCR4 in neonatal rat hippocampus

Alexander Kasyanov, Hirokazu Tamamura, Nobutaka Fujii, Huangui Xiong

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

In the immature hippocampus, the giant depolarizing potentials (GDPs) are recurrent network-driven synaptic events generated by γ-aminobutyric acid (GABA), which in neonatal life is depolarizing and excitatory. The GDPs enable a high degree of synchrony in immature neurons and participate in activity-dependent growth and synapse formation. To understand how human immunodeficiency virus type one (HIV-1) infection in the immature brain impairs brain growth and development, we studied the effects of HIV-1 envelope glycoprotein, gp120, a viral toxin shed in abundance by infected cells, on spontaneous occurring GDPs recorded in the CA3 pyramidal cells in neonatal (P2-P6) Sprague-Dawley rat hippocampal slices using whole-cell patch technique. Bath application of gp120 produced a sustained enhancement of GDP frequency in a concentration-dependent manner without affecting passive membrane properties, suggesting that the site of action is most likely on neural network, other than on the recorded neurons. The gp120-induced enhancement of GDPs was blocked by T140, a highly specific antagonist for the chemokine receptor, CXCR4, indicating the involvement of CXCR4 in the gp120-induced increase of GDPs. Bath application of stromal cell-derived factor-1α (SDF-1α), the only CXCR4 ligand, mimicked the effects of gp120 on GDPs, supporting the engagement of CXCR4 receptors in the gp120-induced increase of GDP occurrence. Further studies revealed the involvement of protein kinase A/C in the gp120-induced enhancement of GDPs. These results demonstrate that gp120 enhances GDPs in the neonatal rat hippocampus. This enhancement may cause an excessive increase in intracellular calcium and resultant neuronal injury, leading to retardation of the brain and behavioural development as seen in paediatric AIDS patients.

Original languageEnglish (US)
Pages (from-to)1120-1128
Number of pages9
JournalEuropean Journal of Neuroscience
Volume23
Issue number5
DOIs
StatePublished - Mar 1 2006

Fingerprint

Chemokine Receptors
HIV-1
Hippocampus
Baths
Brain
HIV Envelope Protein gp120
CXCR4 Receptors
Aminobutyrates
Neurons
Chemokine CXCL12
Pyramidal Cells
Cyclic AMP-Dependent Protein Kinases
Growth and Development
Synapses
Protein Kinase C
HIV Infections
Sprague Dawley Rats
Acquired Immunodeficiency Syndrome
HIV
Pediatrics

Keywords

  • Brain slices
  • EPSPs
  • HIV
  • Patch clamp
  • Sprague-Dawley rat

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

HIV-1 gp120 enhances giant depolarizing potentials via chemokine receptor CXCR4 in neonatal rat hippocampus. / Kasyanov, Alexander; Tamamura, Hirokazu; Fujii, Nobutaka; Xiong, Huangui.

In: European Journal of Neuroscience, Vol. 23, No. 5, 01.03.2006, p. 1120-1128.

Research output: Contribution to journalArticle

Kasyanov, Alexander ; Tamamura, Hirokazu ; Fujii, Nobutaka ; Xiong, Huangui. / HIV-1 gp120 enhances giant depolarizing potentials via chemokine receptor CXCR4 in neonatal rat hippocampus. In: European Journal of Neuroscience. 2006 ; Vol. 23, No. 5. pp. 1120-1128.
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