Preferential enhancement of GluN2B-containing native NMDA receptors by the endogenous modulator 24S-hydroxycholesterol in hippocampal neurons.

ABSTRACT: 24S-hydroxycholesterol (24HC) is the major metabolic breakdown product of cholesterol in the brain. Among its other effects on neurons, 24HC modulates N-methyl-d-aspartate (NMDA or GluN) receptors, but our understanding of this mechanism is poor. We used whole-cell patch clamp recordings and various pharmacological approaches in mouse brain slices to record isolated NMDAR-mediated (I_NMDA) tonic and evoked synaptic currents. 24HC (1 μΜ) significantly enhanced tonic, but not evoked, I_NMDA of dentate gyrus granule cells. The I_NMDA had both GluN2A and GluN2B-mediated components. Preincubation of the slices with PEAQX (a GluN2A antagonist) or Ro25-6981 (a GluN2B antagonist) dramatically changed the I_NMDA modulatory potential of 24HC. Ro25-6981 blocked

SUBMITTER: Wei X 

PROVIDER: S-EPMC6424632 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature