NMDA receptors mediate calcium accumulation in myelin during chemical ischaemia

摘要: Central nervous system myelin is a specialized structure produced by oligodendrocytes that ensheaths axons, allowing rapid and efficient saltatory conduction of action potentials1. Many disorders promote damage to eventual loss the sheath, which often results in significant neurological morbidity. However, little known about fundamental mechanisms initiate damage, with assumption being its fate follows parent oligodendrocyte. Here we show NMDA (N-methyl-d-aspartate) glutamate receptors mediate Ca2+ accumulation central response chemical ischaemia vitro. Using two-photon microscopy, imaged fluorescence indicator X-rhod-1 loaded into cytoplasmic compartment sheath adult rat optic nerves. The AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)/kainate receptor antagonist NBQX2 completely blocked ischaemic increase oligodendroglial cell bodies, but only modestly reduced myelin. In contrast, was abolished broad-spectrum antagonists (MK-801, 7-chlorokynurenic acid, d-AP53,4), not more selective blockers NR2A NR2B subunit-containing (NVP-AAM0775 ifenprodil2,4). vitro causes ultrastructural both axon cylinders myelin6. antagonism greatly NR1, NR2 NR3 subunits were detected immunohistochemistry immunoprecipitation, indicating all necessary are present for formation functional receptors. Our data mature can respond independently injurious stimuli. Given axons release glutamate7,8,9, our finding mediated large part activation myelinic suggests new mechanism axo–myelinic signalling. Such may represent potentially important therapeutic target demyelination prominent feature, such as multiple sclerosis, neurotrauma, infections (for example, HIV encephalomyelopathy) aspects brain injury.