FIGURE 5.

Male Tg26 mice show reduced hippocampal synapsin‐1 levels, decreased GluA1 phosphorylation post fear conditioning and increased hippocampal GSK3β activity. (a) Representative western blots and densitometric analyses of hippocampal pre‐ and post‐synaptic proteins in male and female WT and Tg26 mice. A significant reduction in synapsin‐1 proteins (77 kDa) was observed in male, but not female, Tg26 mice compared to the WT mice. n = 9 for male WT, n = 8 for male Tg26, n = 6 for female WT, n = 5 for female Tg26; *P < 0.05 as compared to WT, unpaired Student's t‐test. The levels of NR1 (100 kDa;n = 5 for male WT, n = 3 for male Tg26, n = 5 for female WT, n = 3 for female Tg26), NR2A (180 kDa; n = 5 for male WT, n = 3 for male Tg26, n = 5 for female WT, n = 3 for female Tg26), NR2B (190 kDa; n = 5 for male WT, n = 3 for male Tg26, n = 5 for female WT, n = 3 for female Tg26), phospho‐Ser831 GluA1 (106 kDa; n = 4 per each group), GluA2/3 (98 kDa; n = 4 per each group), phospho‐Ser418 PSD95 (95 kDa; n = 5 for male WT, n = 3 for male Tg26, n = 5 for female WT, n = 3 for female Tg26), SNAP25 (25 kDa; n = 4 per each group), syntaxin‐1a (33 kDa; n = 8 for male WT, n = 8 for male Tg26, n = 4 for female WT, n = 4 for female Tg26), synaptobrevin (13 kDa; n = 4 per each group), synaptotagmin‐2 (67 kDa; n = 5 for male WT, n = 3 for male Tg26, n = 5 for female WT, n = 3 for female Tg26), gephyrin (93 kDa; n = 5 for male WT, n = 3 for male Tg26, n = 5 for female WT, n = 3 for female Tg26) and synaptophysin (38 kDa; n = 5 for male WT, n = 3 for male Tg26, n = 5 for female WT, n = 3 for female Tg26) proteins were unaltered in male and female Tg26 mice as compared to their respective WT controls. β‐actin (42 kDa) and GAPDH (37 kDa) served as loading controls. (b) Representative western blots and densitometric analysis of hippocampal phospho‐Ser831 GluA1 protein in naïve and fear conditioned male WT and Tg26 mice (n = 8 per each group). Naïve WT and Tg26 mice showed similar levels of phospho‐Ser831 GluA1 proteins, which increased significantly in WT mice 30 min after fear conditioning. In contrast, male Tg26 mice showed a significant reduction in phospho‐Ser831 GluA1 levels post fear conditioning. *P < 0.05 as compared to naïve group, unpaired Student'st‐test. (c) Representative western blots and densitometricanalysis of hippocampal total GSK3α (51 kDa), total GSK3β (46 kDa) and phospho‐Ser9‐GSK3β (46 kDa; inactive form) proteins in male WT and Tg26 mice (n = 7 per each group). Analysis of phospho‐Ser9‐GSK3β/GSK3β ratio showed a significant reduction in male Tg26 mice compared to male WT mice. *P < 0.05, unpaired Student's t‐test. Analysis of GSK3α/β‐actin and GSK3β/β‐actin ratios showed similar levels between male Tg26 and WT mice. β‐actin (42 kDa) served as loading control