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In terms of the expression of second messengers in the PI3K cascade, GLP-1 RAs induced significantly increased phosphorylation of PI3K, Akt, and mTOR compared to the control group.Reference Guan, Xiao and Xie 28 , Reference Palleria, Leo and Andreozzi 40 Notably, GLP-1 RA treatment significantly increased PSD-95 (156% of control, p = 0.020) and synapsin I (174% of control, p = 0.001) expression, which was ameliorated with rapamycin and NBQX.Reference Park, Mansur and Lee 41 Furthermore, in Wistar rats that had 72 hours of rapid eye movement sleep deprivation, there were reduced levels of CaMKII and PSD95 in the hippocampus and prefrontal cortex, which was prevented with GLP-1 RA treatment.Reference Turan, Sayan Ozacmak, Ozacmak, Ergenc and Bayraktarolu 45 Similar trends were observed in rats with Abeta142 treated with GLP-1 RAs wherein there was an increase in the number of phosphorylated CaMKIIalpha-positive cells in the hippocampus.Reference Wang, Wang, Jiang, Yuan, Yu and Li 46 Taken together, GLP-1 RAs effects on synaptic plasticity and neuroprotective effects may be mediated via mTOR subsequent to AMPA receptor activation (Figure 2)