Defective myelination in mice lacking the lysophosphatidic acid receptor LPA1: newcomer models for demyelinating and neuroinflammatory diseases.

Abstract

The LPA1- signalling pathway is directly involved and required for a normal myelination as showed by the subsequent alterations observed in the mice lacking this receptor and affecting quantity, quality and organization of myelinated fibers. - The presence of LP A1 has an important role in trafficking PLP from soma to myelin sheet. The absence of this receptor sticks this protein in the endoplasmic reticulum that correlates with cellular loss in null mice and suggests stress-induced apoptosis. - Accordingly to proposed role for LPA1 in myelinization and maintenance of oligodendrocyte viability, intracistemal administration of LP A following cuprizone-induced demyelination promotes oligodendrocyte proliferation and remyelination processes. - LPA signalling pathway, through LPA1 and LPA2 receptors, contributes to the ongoing of the inflammatory processes in EAE as suggested by the observed modulation of their expressions in PBMCs during the disease. In absence ofLPA1, EAE develops later and has a significantly more benign course corroborating the involvement of the receptor in EAE pathogenesis. - Likewise, the periodical intravenous administration ofLPA1 antagonist resembled the effects of the absence of receptor in maLPA1-null mice with induced EAE.