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Citalopram Attenuates Tau Hyperphosphorylation and Spatial Memory Deficit Induced by Social Isolation Rearing in Middle-Aged Rats

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Abstract

Social isolation (SI) is considered as a chronic stress. Here, middle-aged rats (8 months) were group or isolation reared for 6 weeks. Following the initial two-week period of rearing, citalopram (10 mg/kg i.p.) was administered for 28 days. Changes in recognition memory, depression and anxiety-like behavior, and phosphorylated tau were investigated. We found that SI did not lead to obvious depression/anxiety-like behavior in middle-aged rats. Memory deficits and increased tau hyperphosphorylation at Tau-1, Ser396 episodes could be almost reversed by citalopram. The level of Ser9-phosphorylated GSK-3β (inactive form) was significantly decreased in the SI group which also could be almost reversed by citalopram, suggesting that the citalopram could prevent GSK-3β from SI-induced overactivation. The melatonin level was decreased in SI group compared with group housed (GH) group, and citalopram could partly restore the level of melatonin. We also found that citalopram could increase MT1 and MT2 in mRNA level. Our results demonstrate that citalopram increases the level of melatonin which negatively regulates GSK-3β and attenuates tau hyperphosphorylation and spatial memory deficit induced by SI in middle-aged rats. Suggesting that SI might constitute a risk factor for Alzheimer’s disease (AD), and citalopram may represent a therapeutic strategy for the treatment of AD.

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Acknowledgments

This work was supported in part by grants from the National Natural Science Foundation of China (30900447 and 91232707).

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Authors and Affiliations

  1. Department of Neuropsychiatry, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, China

    Qing-Guo Ren, Wei-Gang Gong, Yan-Juan Wang & Zhi-Jun Zhang

  2. Department of Neurology, Wu Xi Branch of Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Wuxi, China

    Qing-Guo Ren & Qi-Da Zhou

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  1. Qing-Guo Ren
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  2. Wei-Gang Gong
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Correspondence to Qing-Guo Ren.

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Qing-Guo Ren and Wei-Gang Gong contributed equally to this work.

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Ren, QG., Gong, WG., Wang, YJ. et al. Citalopram Attenuates Tau Hyperphosphorylation and Spatial Memory Deficit Induced by Social Isolation Rearing in Middle-Aged Rats. J Mol Neurosci 56, 145–153 (2015). https://doi.org/10.1007/s12031-014-0475-4

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