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Aging and chronic administration of serotonin-selective reuptake inhibitor citalopram upregulate Sirt4 gene expression in the preoptic area of male mice.

Wong DW, Soga T, Parhar IS - Front Genet (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Brain Research Institute, School of Medicine and Health Sciences, Monash University Malaysia Selangor, Malaysia.

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.

No MeSH data available.


Related in: MedlinePlus

Chronic citalopram (CIT) treatment up-regulates sirt2 and sirt4 in the preoptic area. CIT was administered at 10 mg/kg/bodyweight daily in male mice for a duration of 4 weeks leading to relative mRNA changes in sirt2 and sirt4 expression in the POA. There was no difference in sirt3, sirt5, sirt6, or sirt7 mRNA levels in the POA after CIT treatment. Data are expressed as mean ± SEM. Statistical analysis was carried out using one-way analysis of variance (12 weeks control, n = 9; 12 weeks CIT, n = 9). *P < 0.05 vs. control.
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Figure 2: Chronic citalopram (CIT) treatment up-regulates sirt2 and sirt4 in the preoptic area. CIT was administered at 10 mg/kg/bodyweight daily in male mice for a duration of 4 weeks leading to relative mRNA changes in sirt2 and sirt4 expression in the POA. There was no difference in sirt3, sirt5, sirt6, or sirt7 mRNA levels in the POA after CIT treatment. Data are expressed as mean ± SEM. Statistical analysis was carried out using one-way analysis of variance (12 weeks control, n = 9; 12 weeks CIT, n = 9). *P < 0.05 vs. control.

Mentions: Chronic CIT treatment induced an increase in sirt2 (12 weeks 1.00 ± 0.13 vs. 12 weeks CIT 1.61 ± 0.12, p < 0.05) and sirt4 (12 weeks 1.00 ± 0.15 vs. 12 weeks CIT 1.43 ± 0.13, p < 0.05) expression in the POA (Figure 2). There was no difference in sirt3, sirt5, sirt6, and sirt7 levels in the POA after CIT treatment (Figure 2).


Aging and chronic administration of serotonin-selective reuptake inhibitor citalopram upregulate Sirt4 gene expression in the preoptic area of male mice.

Wong DW, Soga T, Parhar IS - Front Genet (2015)

Chronic citalopram (CIT) treatment up-regulates sirt2 and sirt4 in the preoptic area. CIT was administered at 10 mg/kg/bodyweight daily in male mice for a duration of 4 weeks leading to relative mRNA changes in sirt2 and sirt4 expression in the POA. There was no difference in sirt3, sirt5, sirt6, or sirt7 mRNA levels in the POA after CIT treatment. Data are expressed as mean ± SEM. Statistical analysis was carried out using one-way analysis of variance (12 weeks control, n = 9; 12 weeks CIT, n = 9). *P < 0.05 vs. control.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4584971&req=5

Figure 2: Chronic citalopram (CIT) treatment up-regulates sirt2 and sirt4 in the preoptic area. CIT was administered at 10 mg/kg/bodyweight daily in male mice for a duration of 4 weeks leading to relative mRNA changes in sirt2 and sirt4 expression in the POA. There was no difference in sirt3, sirt5, sirt6, or sirt7 mRNA levels in the POA after CIT treatment. Data are expressed as mean ± SEM. Statistical analysis was carried out using one-way analysis of variance (12 weeks control, n = 9; 12 weeks CIT, n = 9). *P < 0.05 vs. control.
Mentions: Chronic CIT treatment induced an increase in sirt2 (12 weeks 1.00 ± 0.13 vs. 12 weeks CIT 1.61 ± 0.12, p < 0.05) and sirt4 (12 weeks 1.00 ± 0.15 vs. 12 weeks CIT 1.43 ± 0.13, p < 0.05) expression in the POA (Figure 2). There was no difference in sirt3, sirt5, sirt6, and sirt7 levels in the POA after CIT treatment (Figure 2).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Brain Research Institute, School of Medicine and Health Sciences, Monash University Malaysia Selangor, Malaysia.

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.

No MeSH data available.


Related in: MedlinePlus