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Sanchez AB, Medders KE, Maung R, et al. CXCL12-induced neurotoxicity critically depends on NMDA receptor-gated and L-type Ca. J Neuroinflammation. 2016;13(1):252doi: 10.1186/s12974-016-0724-2.
Sanchez, A. B., Medders, K. E., Maung, R., Sánchez-Pavón, P., Ojeda-Juárez, D., & Kaul, M. (2016). CXCL12-induced neurotoxicity critically depends on NMDA receptor-gated and L-type Ca. Journal of neuroinflammation, 13(1), 252. https://doi.org/10.1186/s12974-016-0724-2
Sanchez, Ana B, et al. "CXCL12-induced neurotoxicity critically depends on NMDA receptor-gated and L-type Ca." Journal of neuroinflammation vol. 13,1 (2016): 252. doi: https://doi.org/10.1186/s12974-016-0724-2
Sanchez AB, Medders KE, Maung R, Sánchez-Pavón P, Ojeda-Juárez D, Kaul M. CXCL12-induced neurotoxicity critically depends on NMDA receptor-gated and L-type Ca. J Neuroinflammation. 2016 Sep 23;13(1):252. doi: 10.1186/s12974-016-0724-2. PMID: 27664068; PMCID: PMC5035480.
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J Neuroinflammation. 2016 Sep 23;13(1):252. doi: 10.1186/s12974-016-0724-2.

CXCL12-induced neurotoxicity critically depends on NMDA receptor-gated and L-type Ca.

Journal of neuroinflammation

Ana B Sanchez, Kathryn E Medders, Ricky Maung, Paloma Sánchez-Pavón, Daniel Ojeda-Juárez, Marcus Kaul

Affiliations

  1. Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, Bldg. 10, La Jolla, CA, 92037, USA.
  2. Present address: UC San Diego Health, 200 W. Arbor Drive #8765, San Diego, CA, 92103, USA.
  3. Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, Bldg. 10, La Jolla, CA, 92037, USA. [email protected].
  4. Department of Psychiatry, University of California, San Diego, 9500 Gilman Drive, San Diego, CA, 92093, USA. [email protected].

PMID: 27664068 PMCID: PMC5035480 DOI: 10.1186/s12974-016-0724-2

Abstract

BACKGROUND: The chemokine receptor CXCR4 (CD184) and its natural ligand CXCL12 contribute to many physiological processes, including decisions about cell death and survival in the central nervous system. In addition, CXCR4 is a co-receptor for human immunodeficiency virus (HIV)-1 and mediates the neurotoxicity of the viral envelope protein gp120. However, we previously observed that CXCL12 also causes toxicity in cerebrocortical neurons but the cellular mechanism remained incompletely defined.

METHODS: Primary neuronal-glial cerebrocortical cell cultures from rat were exposed to a neurotoxicity-inducing CXCL12 concentration for different times and the activity of the stress-associated mitogen-activated protein kinase p38 (p38 MAPK) was assessed using an in vitro kinase assay. Neurotoxicity of CXCL12 and cellular localization of p38 MAPK was analyzed by immunofluorescence microscopy. Pharmacological inhibition of NMDA-type glutamate receptor-gated ion channels (NMDAR) of L-type Ca

RESULTS: Here, we show that a neurotoxic amount of CXCL12 triggers a significant increase of endogenous p38 MAPK activity in cerebrocortical cells. Immunofluorescence and Western blotting experiments with mixed neuronal-glial and neuron-depleted glial cerebrocortical cells revealed that the majority of active/phosphorylated p38 MAPK was located in neurons. Blockade of NMDAR-gated ion channels or L-type Ca

CONCLUSIONS: Our findings link CXCL12-induced neuronal death to the regulation of NMDAR-gated ion channels and L-type Ca

Keywords: CXCL12; CXCR4; Calcium channel; Cell death; Immunofluorescence microscopy; Inhibitors; Kinase activity; Neurotoxicity; p38 MAPK

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