These findings highlight the importance of mental health of females before pregnancy and suggest that CUS before pregnancy reduces p-CREB and p-NR2B in the offspring hippocampus, which could be responsible for behavioral disorders in the adolescent offspring.
Taken together, our results revealed a specific enhancement of GluN2B-containing NMDARs by 24HC, indicating a novel endogenous pathway to influence a subclass of NMDARs critically involved in cortical plasticity and in numerous neurological and psychiatric disorders.
We also used gap-prepulse inhibition of the acoustic startle reflex (GPIAS) and noise burst prepulse inhibition of acoustic startle, and the auditory brainstem level (electrophysiological recordings of auditory brainstem responses, ABR) and NR2B expression level in the auditory cortex to evaluate whether memantine could reduce salicylate-mediated behavioral disturbances.
The pathogenic relevance of NMDAR autoantibodies to behavioral abnormalities (blunted response to amphetamine-triggered activity and decreased locomotor activity and exploration) and reduced expression of synaptic proteins (the GLUN2B subtype of NMDAR and PSD-95) has been demonstrated in infected mice.
Mutations in the GRIN2B gene (MRD6, MIM613970) have been identified as a common cause of ID (prevalence of 0.5 - 1% in individuals with ID) associated with EEG and behavioral problems.
In wild-type mice, systemic treatment with the NR2B antagonist, Ro25-6981 [R-(R,S)-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1-piperidine propranol], and hippocampal small interfering RNA-mediated NR2B/Grin2b knockdown resulted in behavioral changes similar to those elicited by the Setdb1 transgene.
NR2B Y1472 is hypophosphorylated in NRG1+/- mutant mice, and this defect can be reversed by clozapine at a dose that reverses their behavioral abnormalities.