Aging and Chronic Administration of Serotonin-selective Reuptake Inhibitor Citalopram Upregulate Sirt4 Gene Expression in the Preoptic Area of Male Mice

Overview

Journal Front Genet

Date 2015 Oct 7

PMID 26442099

Citations 5

Authors

Dutt Way Wong

Tomoko Soga

Ishwar S Parhar

Affiliations

Soon will be listed here.

Abstract

Sexual dysfunction and cognitive deficits are markers of the aging process. Mammalian sirtuins (SIRT), encoded by sirt 1-7 genes, are known as aging molecules which are sensitive to serotonin (5-hydroxytryptamine, 5-HT). Whether the 5-HT system regulates SIRT in the preoptic area (POA), which could affect reproduction and cognition has not been examined. Therefore, this study was designed to examine the effects of citalopram (CIT, 10 mg/kg for 4 weeks), a potent selective-serotonin reuptake inhibitor and aging on SIRT expression in the POA of male mice using real-time PCR and immunocytochemistry. Age-related increases of sirt1, sirt4, sirt5, and sirt7 mRNA levels were observed in the POA of 52 weeks old mice. Furthermore, 4 weeks of chronic CIT treatment started at 8 weeks of age also increased sirt2 and sirt4 mRNA expression in the POA. Moreover, the number of SIRT4 immuno-reactive neurons increased with aging in the medial septum area (12 weeks = 1.00 ± 0.15 vs. 36 weeks = 1.68 ± 0.14 vs. 52 weeks = 1.54 ± 0.11, p < 0.05). In contrast, the number of sirt4-immunopositive cells did not show a statistically significant change with CIT treatment, suggesting that the increase in sirt4 mRNA levels may occur in cells in which sirt4 is already being expressed. Taken together, these studies suggest that CIT treatment and the process of aging utilize the serotonergic system to up-regulate SIRT4 in the POA as a common pathway to deregulate social cognitive and reproductive functions.

Citing Articles

The Structures, Functions, and Roles of Class III HDACs (Sirtuins) in Neuropsychiatric Diseases.

Bonomi R, Riordan W, Gelovani J Cells. 2024; 13(19.

PMID: 39404407 PMC: 11476333. DOI: 10.3390/cells13191644.

Development of a mitochondrial sirtuin 4 FRET assay based on its activity for removing 3-hydroxy-3-methylglutaryl (HMG) modification.

Li Y, Zhao Y, Cao Z, Wang J, Liu T, Li Y RSC Adv. 2022; 11(5):2677-2681.

PMID: 35747080 PMC: 9133976. DOI: 10.1039/d0ra09424b.

Mitochondrial Function, Metabolic Regulation, and Human Disease Viewed through the Prism of Sirtuin 4 (SIRT4) Functions.

Betsinger C, Cristea I J Proteome Res. 2019; 18(5):1929-1938.

PMID: 30913880 PMC: 6889813. DOI: 10.1021/acs.jproteome.9b00086.

Knock-out of a mitochondrial sirtuin protects neurons from degeneration in Caenorhabditis elegans.

Sangaletti R, DAmico M, Grant J, Della-Morte D, Bianchi L PLoS Genet. 2017; 13(8):e1006965.

PMID: 28820880 PMC: 5576752. DOI: 10.1371/journal.pgen.1006965.

Sirtuins and Their Roles in Brain Aging and Neurodegenerative Disorders.

Jesko H, Wencel P, Strosznajder R, Strosznajder J Neurochem Res. 2016; 42(3):876-890.

PMID: 27882448 PMC: 5357501. DOI: 10.1007/s11064-016-2110-y.

References

Davidson J, Chen J, Crapo L, Gray G, Greenleaf W, Catania J . Hormonal changes and sexual function in aging men. J Clin Endocrinol Metab. 1983; 57(1):71-7. DOI: 10.1210/jcem-57-1-71. View

Barrientos R, Frank M, Watkins L, Maier S . Aging-related changes in neuroimmune-endocrine function: implications for hippocampal-dependent cognition. Horm Behav. 2012; 62(3):219-27. PMC: 3371098. DOI: 10.1016/j.yhbeh.2012.02.010. View

Nakamura T, Nakamura W, Yamazaki S, Kudo T, Cutler T, Colwell C . Age-related decline in circadian output. J Neurosci. 2011; 31(28):10201-5. PMC: 3155746. DOI: 10.1523/JNEUROSCI.0451-11.2011. View

Bronson F, Desjardins C . Endocrine responses to sexual arousal in male mice. Endocrinology. 1982; 111(4):1286-91. DOI: 10.1210/endo-111-4-1286. View

Montejo A, Llorca G, Izquierdo J, Rico-Villademoros F . Incidence of sexual dysfunction associated with antidepressant agents: a prospective multicenter study of 1022 outpatients. Spanish Working Group for the Study of Psychotropic-Related Sexual Dysfunction. J Clin Psychiatry. 2001; 62 Suppl 3:10-21. View

Kondo Y, Yamanouchi K . Potentiation of ejaculatory activity by median raphe nucleus lesions in male rats: effect of p-chlorophenylalanine. Endocr J. 1998; 44(6):873-9. DOI: 10.1507/endocrj.44.873. View

Soga T, Wong D, Clarke I, Parhar I . Citalopram (antidepressant) administration causes sexual dysfunction in male mice through RF-amide related peptide in the dorsomedial hypothalamus. Neuropharmacology. 2010; 59(1-2):77-85. DOI: 10.1016/j.neuropharm.2010.03.018. View

Ferguson J, Young L, Insel T . The neuroendocrine basis of social recognition. Front Neuroendocrinol. 2002; 23(2):200-24. DOI: 10.1006/frne.2002.0229. View

Sibille E, Su J, Leman S, Le Guisquet A, Ibarguen-Vargas Y, Joeyen-Waldorf J . Lack of serotonin1B receptor expression leads to age-related motor dysfunction, early onset of brain molecular aging and reduced longevity. Mol Psychiatry. 2007; 12(11):1042-56, 975. PMC: 2515886. DOI: 10.1038/sj.mp.4001990. View

10.

Casadesus G, Milliken E, Webber K, Bowen R, Lei Z, Rao C . Increases in luteinizing hormone are associated with declines in cognitive performance. Mol Cell Endocrinol. 2007; 269(1-2):107-11. DOI: 10.1016/j.mce.2006.06.013. View

11.

De Marte M, Enesco H . Influence of low tryptophan diet on survival and organ growth in mice. Mech Ageing Dev. 1986; 36(2):161-71. DOI: 10.1016/0047-6374(86)90017-5. View

12.

Larsson K, Heimer L . MATING BEHAVIOUR OF MALE RATS AFTER LESIONS IN THE PREOPTIC AREA. Nature. 1964; 202:413-4. DOI: 10.1038/202413a0. View

13.

Delgado P, Charney D, Price L, Aghajanian G, Landis H, Heninger G . Serotonin function and the mechanism of antidepressant action. Reversal of antidepressant-induced remission by rapid depletion of plasma tryptophan. Arch Gen Psychiatry. 1990; 47(5):411-8. DOI: 10.1001/archpsyc.1990.01810170011002. View

14.

Abe N, Uchida S, Otsuki K, Hobara T, Yamagata H, Higuchi F . Altered sirtuin deacetylase gene expression in patients with a mood disorder. J Psychiatr Res. 2011; 45(8):1106-12. DOI: 10.1016/j.jpsychires.2011.01.016. View

15.

Tsutsumi R, Webster N . GnRH pulsatility, the pituitary response and reproductive dysfunction. Endocr J. 2009; 56(6):729-37. PMC: 4307809. DOI: 10.1507/endocrj.k09e-185. View

16.

Pettan-Brewer C, Touch D, Wiley J, Hopkins H, Rabinovitch P, Ladiges W . A novel radial water tread maze tracks age-related cognitive decline in mice. Pathobiol Aging Age Relat Dis. 2013; 3. PMC: 3791354. DOI: 10.3402/pba.v3i0.20679. View

17.

ELEFTHERIOU B, LUCAS L . Age-related changes in testes, seminal vesicles and plasma testosterone levels in male mice. Gerontologia. 1974; 20(4):231-8. DOI: 10.1159/000212019. View

18.

Komlos D, Mann K, Zhuo Y, Ricupero C, Hart R, Liu A . Glutamate dehydrogenase 1 and SIRT4 regulate glial development. Glia. 2013; 61(3):394-408. PMC: 3552040. DOI: 10.1002/glia.22442. View

19.

Dali-Youcef N, Lagouge M, Froelich S, Koehl C, Schoonjans K, Auwerx J . Sirtuins: the 'magnificent seven', function, metabolism and longevity. Ann Med. 2007; 39(5):335-45. DOI: 10.1080/07853890701408194. View

20.

Michaelis E, Wang X, Pal R, Bao X, Hascup K, Wang Y . Neuronal Glud1 (glutamate dehydrogenase 1) over-expressing mice: increased glutamate formation and synaptic release, loss of synaptic activity, and adaptive changes in genomic expression. Neurochem Int. 2011; 59(4):473-81. PMC: 3152645. DOI: 10.1016/j.neuint.2011.03.003. View