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Modulation of LPA Receptor Expression in the Human Brain Following Neurotrauma

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Abstract

Lysophosphatidic acid (LPA) is involved in physiological and pathological states, including in neural development and inflammation. We assessed the expression pattern of the LPA receptors 1-3 and of LPA-producing enzyme autotaxin in post-mortem human brain tissue, both in normal individuals and in individuals who died following traumatic brain injury. We found that LPA receptors and autotaxin are weakly expressed in the normal control adult brain. Quantitative PCR for the LPA receptors and autotaxin mRNA showed an increase of LPAR2 and a decrease of autotaxin mRNA expression in the cortex following brain injury. Immunohistochemical analysis showed that LPAR1 colocalized with astrocytes and that LPAR2 is present on the ependymal cells lining the lateral ventricle in the brain samples from individuals who died following severe head injury. This work shows for the first time that key components of the LPA pathway are modulated following TBI in humans.

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Abbreviations

ATX:

Autotaxin

CNS:

Central nervous system

CSF:

Cerebrospinal fluid

LPA:

Lysophosphatidic acid

TBI:

Traumatic brain injury

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Acknowledgments

This work was supported by a NHMRC Project Grant 454723, a NHMRC/Victorian Neurotrauma Initiative Career Development Award (to AP) and the Victorian State Government’s Department of Innovation, Industry and Regional Development’s Operational Infastructure Support Program. Tissues were received from the Victorian Brain Bank Network, supported by The National Trauma Research Institute, The University of Melbourne, The Mental Health Research Institute of Victoria, The Victorian Institute of Forensic Medicine and funded by the Victorian Neurotrauma Initiative, Neurosciences Australia and the NHMRC. The authors wish to thank the Histology Facility, Department of Anatomy and Cell Biology, University of Melbourne and J. Palmer for their technical assistance.

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Correspondence to Alice Pébay.

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Frugier, T., Crombie, D., Conquest, A. et al. Modulation of LPA Receptor Expression in the Human Brain Following Neurotrauma. Cell Mol Neurobiol 31, 569–577 (2011). https://doi.org/10.1007/s10571-011-9650-0

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  • DOI: https://doi.org/10.1007/s10571-011-9650-0

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