Tubastatin A ameliorated sevoflurane-induced decreases in synaptophysin and PSD95 expression during development, as well as synaptic ultrastructural damage and cognitive deficits in adulthood.
The overexpression of NL1 can upregulate the expression levels of PV, Nrx1β and PSD95 in mice with POCD, enhance the interaction between NL1 and Nrx1β and further increase the excitability of PV interneurons, thus restoring the hippocampus-dependent memorial and cognitive impairment in POCD.
Importantly, an RPS23RG1-derived peptide comprising a unique PSD-93/PSD-95 interaction motif rescued synaptic and cognitive defects in Rps23rg1 knockout and AD mouse models.
Consistent with these results, ACR caused cognitive defects in the night period by down-regulating the ERK/cAMP response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathways and the expression of synaptosomal-related protein SNAP-25 and PSD-95.
Using Sprague-Dawley rats developmentally exposed to sodium fluoride (NaF) from pregnancy until 6 months of delivery as in vivo model, we showed that fluoride impaired the cognitive abilities of offspring rats, decreased the density of dendritic spines and the expression of synapse proteins synaptophysin (SYN) and postsynaptic density protein-95 (PSD-95) in hippocampus, suggesting fluoride-induced cognitive deficit associates with synaptic impairment.
Taken together, these data suggest that the selective loss of those highly plastic thin spines with sparse postsynaptic density protein-95 and GluR1 receptors may significantly contribute to cognitive deficits in aged individuals.
The treatment of PTEN inhibitor BPV (pic) restored PSD-95 synthesis, and attenuated tau phosphorylation as well as the cognitive dysfunction caused by the repeated isoflurane exposures.