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Modulation of LPA Receptor Expression in the Human Brain Following Neurotrauma
Authors:Tony Frugier  Duncan Crombie  Alison Conquest  Frisca Tjhong  Caroline Taylor  Tejal Kulkarni  Catriona McLean  Alice Pébay
Institution:(1) National Trauma Research Institute, The Alfred Hospital and Department of Medicine, Monash University, Melbourne, VIC, 3004, Australia;(2) O’Brien Institute, Fitzroy, VIC, 3065, Australia;(3) Anatomical Pathology Department, The Alfred Hospital, Melbourne, VIC, 3004, Australia;(4) Centre for Neuroscience, Department of Pharmacology, University of Melbourne, Parkville, VIC, 3010, Australia;
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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