Fractalkine/CX 3CL1 protects striatal neurons from synergistic morphine and HIV-1 Tat-induced dendritic losses and death Article

Suzuki, M, El-Hage, N, Zou, S et al. (2011). Fractalkine/CX 3CL1 protects striatal neurons from synergistic morphine and HIV-1 Tat-induced dendritic losses and death . 6(1), 10.1186/1750-1326-6-78

cited authors

  • Suzuki, M; El-Hage, N; Zou, S; Hahn, YK; Sorrell, ME; Sturgill, JL; Conrad, DH; Knapp, PE; Hauser, KF



  • Background: Fractalkine/CX 3CL1 and its cognate receptor CX 3CR1 are abundantly expressed in the CNS. Fractalkine is an unusual C-X3-C motif chemokine that is important in neuron-microglial communication, a co-receptor for HIV infection, and can be neuroprotective. To assess the effects of fractalkine on opiate-HIV interactive neurotoxicity, wild-type murine striatal neurons were co-cultured with mixed glia from the striata of wild-type or Cx3cr1 knockout mice HIV-1 Tat and/or morphine. Time-lapse digital images were continuously recorded at 20 min intervals for up to 72 h using computer-aided microscopy to track the same cells repeatedly. Results: Co-exposure to Tat and morphine caused synergistic increases in neuron death, dendritic pruning, and microglial motility as previously reported. Exogenous fractalkine prevented synergistic Tat and morphine-induced dendritic losses and neuron death even though the inflammatory mediator TNF- remained significantly elevated. Antibody blockade of CX 3CR1 mimicked the toxic effects of morphine plus Tat, but did not add to their toxicity; while fractalkine failed to protect wild-type neurons co-cultured with Cx 3cr1 -/--null glia against morphine and Tat toxicity. Exogenous fractalkine also normalized microglial motility, which is elevated by Tat and morphine co-exposure, presumably limiting microglial surveillance that may lead to toxic effects on neurons. Fractalkine immunofluorescence was expressed in neurons and to a lesser extent by other cell types, whereas CX 3CR1 immunoreactivity or GFP fluorescence in cells cultured from the striatum of Cx3cr1 -/- (Cx3cr1 GFP/GFP) mice were associated with microglia. Immunoblotting shows that fractalkine levels were unchanged following Tat and/or morphine exposure and there was no increase in released fractalkine as determined by ELISA. By contrast, CX 3CR1 protein levels were markedly downregulated. Conclusions: The results suggest that deficits in fractalkine-CX 3CR1 signaling contribute to the synergistic neurotoxic effects of opioids and Tat. Importantly, exogenous fractalkine can selectively protect neurons from the injurious effects of chronic opioid-HIV-1 Tat co-exposure, and this suggests a potential therapeutic course for neuroAIDS. Although the cellular mechanisms underlying neuroprotection are not certain, findings that exogenous fractalkine reduces microglial motility and fails to protect neurons co-cultured with Cx3cr1 -/- mixed glia suggest that fractalkine may act by interfering with toxic microglial-neuron interactions. © 2011 Suzuki et al; licensee BioMed Central Ltd.

publication date

  • November 18, 2011

Digital Object Identifier (DOI)


  • 6


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