AM281, a CB1 receptor antagonist, reversed the TBI-reduced NMDA receptor subunits NR2B in the hippocampus and ameliorate the spatial learning and memory impairment at 7 d post-TBI, suggesting CB1 receptor is involved in the TBI-induced hippocampal-dependent spatial learning and memory impairment.
Therefore, we also investigated the dynamic of other protein markers involved in cognition and memory impairment such as metabotropic glutamate receptor 5 (mGluR5), ionotropic NMDA receptor (NMDAR2B), prion protein (PrPc) and amyloid precursor protein (APP), whose activity depends on membrane lipid organization.
We found that the activation of GABA<sub>A</sub>Rs (diazepam) and the inactivation of GluN2B-NMDARs (Ro25-6981) or 5-HT<sub>1A</sub>R ((S)-WAY100135) resulted in memory impairment.
These molecular, cellular and behavioral alterations induced by EphB2 inactivation were reversed by NR2B antagonist Ro25-6981, suggesting that EphB2 functions to prevent the progression of depression-like behavior and memory impairment by downregulating NR2B.
Chronic GluN2B antagonism disrupts behavior in wild-type mice without protecting against synapse loss or memory impairment in Alzheimer's disease mouse models.
TTBK1-Tg mice show significant age-dependent memory impairment as determined by radial arm water maze test, which is associated with enhancement of tau and neurofilament phosphorylation, increased levels of p25 and p35, both activators of cyclin-dependent protein kinase 5 (CDK5), enhanced calpain I activity, and reduced levels of hippocampal NMDA receptor types 2B (NR2B) and D. Enhanced CDK5/p35 complex formation is strongly correlated with dissociation of F-actin from p35, suggesting the inhibitory mechanism of CDK5/p35 complex formation by F-actin.