Lithium, phenserine, memantine and pioglitazone reverse memory deficit and restore phospho-GSK3β decreased in hippocampus in intracerebroventricular streptozotocin induced memory deficit model

Role of GSK3<i>β</i> and PP2A on Regulation of Tau Phosphorylation in Hippocampus and Memory Impairment in ICV-STZ Animal Model of Alzheimer’s Disease

“…Consistent with these results, in our laboratory, we found that insufficient inhibitory GSK3β control in STZ-icv rats was demonstrated by a decrease in p-GSK3β levels in the hippocampus, which was associated to STM and LTM impairment (38). Additionally, lithium (GSK3 inhibitor) and pioglitazone (insulin sensitizer) treatment reversed this memory deficit and restored the inhibitory activity of GSK3β in hippocampus [38]. Similarly, other studies have demonstrated that specific inhibition GSK3 activity by lithium prevents hyperphosphorylation of tau, and spatial memory loss resulting from inhibiting the PI3K and PKC [67].…”

“…Our results showed decrease in p-GSK3β and p-GSK3β/total GSK3β ratio; this indirectly suggested an increase in the active GSK3β form, therefore, this might explain the consequent increase of p-tau. Consistent with these results, in our laboratory, we found that insufficient inhibitory GSK3β control in STZ-icv rats was demonstrated by a decrease in p-GSK3β levels in the hippocampus, which was associated to STM and LTM impairment (38). Additionally, lithium (GSK3 inhibitor) and pioglitazone (insulin sensitizer) treatment reversed this memory deficit and restored the inhibitory activity of GSK3β in hippocampus [38].…”

“…The criterion was that once the animal ate all 50 food-pellets and presented 150 nose-pokes (as measured by a photocell) into the food-magazine, the autoshaping training program was initiated [35] [37]. The autoshaping program had been reported previously [37] [38], and this consisted of discrete trials. A trial began with the presentation of a retractable and illuminated lever for 8 s (conditioned stimulus; CS) followed by a food-pellet (unconditioned stimulus; US) delivery.…”

“…As previously reported [38], the rats treated with CB or STZ were sacrificed by decapitation after the autoshaping testing session at 6 months ( For calibration curve bovine serum albumin (BSA) standard was used (Sigma). Figure 1.…”

What have we learned from the streptozotocin-induced animal model of sporadic Alzheimer’s disease, about the therapeutic strategies in Alzheimer’s research

“…In line with these similarities in the pathophysiological background, testing of the therapeutic potential of memantine in the STZ-icv rat model revealed that the memory impairment induced by 3 mg/kg STZ-icv dose in rats was successfully reversed by a 2-week memantine treatment with a 5 mg/kg i.p. dose (Ponce-Lopez et al 2011). However, the memory functions were tested by food magazine and autoshaping training while there is no data on spatial memory in the Morris Water Maze test.…”