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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

Aging induces sirt gene expression in the preoptic area. (A) Representative brain sections depicting areas dissected for gene expression studies in the POA. (B) Quantitative real-time PCR revealed differential sirt expression changes. Data are expressed as mean ± SEM. Statistical analysis was carried out using one-way analysis of variance (12 weeks control, n = 9; 36 weeks, n = 8; 52 weeks, n = 10). *P < 0.05 and #P < 0.01 vs. control.
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Figure 1: Aging induces sirt gene expression in the preoptic area. (A) Representative brain sections depicting areas dissected for gene expression studies in the POA. (B) Quantitative real-time PCR revealed differential sirt expression changes. Data are expressed as mean ± SEM. Statistical analysis was carried out using one-way analysis of variance (12 weeks control, n = 9; 36 weeks, n = 8; 52 weeks, n = 10). *P < 0.05 and #P < 0.01 vs. control.

Mentions: At various ages (12weeks, 12weeks CIT, 36weeks, and 52weeks), animals were deeply anaethesized with an i.p. injection of ketamine xylazine (4.5 mg/kg/BW) followed by rapid removal of the brain and snap frozen. The POA (bregma +0.98 to +0.26, 8–11 sections/brain) was cut on a cryostat (60 μm/section) and each section further dissected with a sterile blade under naked eye (Figure 1A). Total RNA from these tissues was extracted using TRIzol (Invitrogen, Carlsbad, CA, USA) and transcribed using High Capacity Transcription Kit (Applied Biosystems, Foster City, CA, USA) according to manufacturer's protocols. Quantitative real-time PCR was performed on a ABI 7300 (Applied Biosystems Foster City, CA, USA) using 2X Power SYBR Green PCR mix (Applied Biosystems), and 0.2M primers for sirt1-7, nam, and nmnat-1 (Supplementary Table 1) in a final volume of 10 μl. The resulting PCR products were validated using an ABI PRISM 310 Genetic Analyzer and Sequence Analysis Software (Applied Biosystems) and ran on a 2.5% agarose gel with ethidium bromide used for visualization.


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)

Aging induces sirt gene expression in the preoptic area. (A) Representative brain sections depicting areas dissected for gene expression studies in the POA. (B) Quantitative real-time PCR revealed differential sirt expression changes. Data are expressed as mean ± SEM. Statistical analysis was carried out using one-way analysis of variance (12 weeks control, n = 9; 36 weeks, n = 8; 52 weeks, n = 10). *P < 0.05 and #P < 0.01 vs. control.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4584971&req=5

Figure 1: Aging induces sirt gene expression in the preoptic area. (A) Representative brain sections depicting areas dissected for gene expression studies in the POA. (B) Quantitative real-time PCR revealed differential sirt expression changes. Data are expressed as mean ± SEM. Statistical analysis was carried out using one-way analysis of variance (12 weeks control, n = 9; 36 weeks, n = 8; 52 weeks, n = 10). *P < 0.05 and #P < 0.01 vs. control.
Mentions: At various ages (12weeks, 12weeks CIT, 36weeks, and 52weeks), animals were deeply anaethesized with an i.p. injection of ketamine xylazine (4.5 mg/kg/BW) followed by rapid removal of the brain and snap frozen. The POA (bregma +0.98 to +0.26, 8–11 sections/brain) was cut on a cryostat (60 μm/section) and each section further dissected with a sterile blade under naked eye (Figure 1A). Total RNA from these tissues was extracted using TRIzol (Invitrogen, Carlsbad, CA, USA) and transcribed using High Capacity Transcription Kit (Applied Biosystems, Foster City, CA, USA) according to manufacturer's protocols. Quantitative real-time PCR was performed on a ABI 7300 (Applied Biosystems Foster City, CA, USA) using 2X Power SYBR Green PCR mix (Applied Biosystems), and 0.2M primers for sirt1-7, nam, and nmnat-1 (Supplementary Table 1) in a final volume of 10 μl. The resulting PCR products were validated using an ABI PRISM 310 Genetic Analyzer and Sequence Analysis Software (Applied Biosystems) and ran on a 2.5% agarose gel with ethidium bromide used for visualization.

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