Citalopram attenuates tau hyperphosphorylation of cortex and memory deficits in social isolation-reared rats

Abstract

Objective To explore the effect of citalopram on tau phosphorylation and memory deficits induced by social isolation (SI) in adult rats. Methods Sixty Sprague-Dawley adult rats (8 months) were grouped or isolation reared for six-weeks. Following the initial two-week period of rearing, citalopram (10 mg/kg, i.p.) was administered for 4 weeks. Novel object recognition test, Western blot and ELISA were used to detect recognitive function, the levels of tau and GSK-3β protein, and melatonin level respectively. Results In the novel object recognition test, compared with the citalopram group(0.71±0.05) and housed group(0.73±0.13), discrimination ratio(0.48±0.15) in SI group was significant decreased (P<0.05). Tau hyperphosphorylation at Tau-1 ((0.88±0.11)), Ser396 (3.94±0.74) episodes were found and almost reversed by citalopram at Tau-1 (1.56±0.17), Ser396 (2.31±0.24) episodes in SI group. Compared with GH group, the total level of GSK-3β(1.12±0.09) was significantly increased, while the level of Ser9-phosphorylated GSK-3β (inactive form) (0.47±0.11) was significantly decreased in the SI group, both of which were reversed by citalopram (GSK-3β (0.87±0.08) and Ser9-phosphorylated GSK-3β (0.80±0.07)). The melatonin level was decreased in SI group ((359.54±18.80)pg/ml), and citalopram could partly restore the level of melatonin (418.15±18.72)pg/ml, P<0.05). Conclusion The results demonstrate that citalopram increases the level of melatonin which negatively regulates GSK-3β and attenuates tau hyperphosphorylation and memory deficits induced by SI in adult rats. Key words: Social isolation; tau protein; Citalopram; Alzheimer's disease; Melatonin