Complement anaphylatoxin C5a neuroprotects through regulation of glutamate receptor subunit 2 in vitro and in vivo

doi:10.1186/1742-2094-5-5

Journal of Neuroinflammation

Volume 5

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Short report

Complement anaphylatoxin C5a neuroprotects through regulation of glutamate receptor subunit 2 in vitro and in vivo

Piali Mukherjee¹^,4 , Sunil Thomas¹ and Giulio Maria Pasinetti¹^,2^,3

¹Department of Psychiatry, Mount Sinai School of Medicine, 1 Gustav L., Levy Place, New York, NY 10029, USA

²Department of Neuroscience, Mount Sinai School of Medicine, New York, USA

³Geriatric Research and Clinical Center, James J. Peters Veteran Affairs Medical Center, 130 West Kingsbridge Road, Bronx, NY 10468, USA

⁴HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Medical College of Cornell University, New York, NY, USA

author email corresponding author email

Journal of Neuroinflammation 2008, 5:5doi:10.1186/1742-2094-5-5


Published:	29 January 2008

Abstract

Background

The complement system is thought to be involved in the pathogenesis of numerous neurological diseases. We previously reported that pre-treatment of murine cortico-hippocampal neuronal cultures with the complement derived anaphylatoxin C5a, protects against glutamate mediated apoptosis. Our present study with C5a receptor knock out (C5aRKO) mice corroborates that the deficiency of C5a renders C5aRKO mouse more susceptible to apoptotic injury in vivo. In this study we explored potential upstream mechanisms involved in C5a mediated neuroprotection in vivo and in vitro.

Methods

Based on evidence suggesting that reduced expression of glutamate receptor subunit 2 (GluR2) may influence apoptosis in neurons, we studied the effect of human recombinant C5a on GluR2 expression in response to glutamate neurotoxicity. Glutamate analogs were injected into C5aRKO mice or used to treat in vitro neuronal culture and GluR2 expression were assessed in respect with cell death.

Results

In C5aRKO mice we found that the neurons are more susceptible to excitotoxicity resulting in apoptotic injury in the absence of the C5a receptor compared to WT control mice. Our results suggest that C5a protects against apoptotic pathways in neurons in vitro and in vivo through regulation of GluR2 receptor expression.

Conclusion

Complement C5a neuroprotects through regulation of GluR2 receptor subunit.