4.5 Article

Modulation of LPA Receptor Expression in the Human Brain Following Neurotrauma

Journal

CELLULAR AND MOLECULAR NEUROBIOLOGY
Volume 31, Issue 4, Pages 569-577

Publisher

SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10571-011-9650-0

Keywords

Autotaxin; Human; Lysophosphatidic acid; Traumatic brain injury human brain

Funding

  1. NHMRC [454723]
  2. NHMRC/Victorian Neurotrauma Initiative Career Development Award
  3. Victorian State Government's Department of Innovation
  4. Industry and Regional Development's Operational Infastructure Support Program
  5. National Trauma Research Institute
  6. University of Melbourne
  7. Mental Health Research Institute of Victoria
  8. Victorian Institute of Forensic Medicine
  9. Victorian Neurotrauma Initiative, Neurosciences Australia

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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 LPAR(2) and a decrease of autotaxin mRNA expression in the cortex following brain injury. Immunohistochemical analysis showed that LPAR(1) colocalized with astrocytes and that LPAR(2) 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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