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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 but not citalopram (CIT) induced SIRT4 immunoreactive cells in the medial septum (MS). (A) SIRT4 in the POA was observed to be highly co-localized with neuronal nuclei (NeuN) compared to glial fibrillary acidic protein (GFAP) Scale bar = 10 μm. (B) SIRT4 immunoreactive cell counts revealed up-regulation of SIRT4 during aging in the MS but not in the organum vasculosum of the lamina terminalis (OVLT) and anterior hypothalamic area (AHA). However, CIT treatment did not alter any SIRT4 immunoreactive cell counts. (C) High magnification image of SIRT4 staining in MS of 12 weeks and 52 weeks. Scale bar = 50 μm. Data are expressed as mean ± SEM. Statistical analysis was carried out using analysis of variance, #P < 0.01 vs. control.
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Figure 5: Aging but not citalopram (CIT) induced SIRT4 immunoreactive cells in the medial septum (MS). (A) SIRT4 in the POA was observed to be highly co-localized with neuronal nuclei (NeuN) compared to glial fibrillary acidic protein (GFAP) Scale bar = 10 μm. (B) SIRT4 immunoreactive cell counts revealed up-regulation of SIRT4 during aging in the MS but not in the organum vasculosum of the lamina terminalis (OVLT) and anterior hypothalamic area (AHA). However, CIT treatment did not alter any SIRT4 immunoreactive cell counts. (C) High magnification image of SIRT4 staining in MS of 12 weeks and 52 weeks. Scale bar = 50 μm. Data are expressed as mean ± SEM. Statistical analysis was carried out using analysis of variance, #P < 0.01 vs. control.

Mentions: SIRT4 immunoreactive cells were observed in the MS, OVLT and AHA regions (Figure 4). We observed SIRT4 protein localized mainly in neurons compared to glial cells in the POA (Figure 5A). SIRT4 co-localization with glial cells were observed in areas close to the third ventricle of the preoptic area whereas the vast majority of SIRT4 immunoreactivity was observed in neurons. There was no immunostaining when the antibody was preadsorbed with its corresponding antigen or when the antibody was excluded.


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 but not citalopram (CIT) induced SIRT4 immunoreactive cells in the medial septum (MS). (A) SIRT4 in the POA was observed to be highly co-localized with neuronal nuclei (NeuN) compared to glial fibrillary acidic protein (GFAP) Scale bar = 10 μm. (B) SIRT4 immunoreactive cell counts revealed up-regulation of SIRT4 during aging in the MS but not in the organum vasculosum of the lamina terminalis (OVLT) and anterior hypothalamic area (AHA). However, CIT treatment did not alter any SIRT4 immunoreactive cell counts. (C) High magnification image of SIRT4 staining in MS of 12 weeks and 52 weeks. Scale bar = 50 μm. Data are expressed as mean ± SEM. Statistical analysis was carried out using analysis of variance, #P < 0.01 vs. control.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4584971&req=5

Figure 5: Aging but not citalopram (CIT) induced SIRT4 immunoreactive cells in the medial septum (MS). (A) SIRT4 in the POA was observed to be highly co-localized with neuronal nuclei (NeuN) compared to glial fibrillary acidic protein (GFAP) Scale bar = 10 μm. (B) SIRT4 immunoreactive cell counts revealed up-regulation of SIRT4 during aging in the MS but not in the organum vasculosum of the lamina terminalis (OVLT) and anterior hypothalamic area (AHA). However, CIT treatment did not alter any SIRT4 immunoreactive cell counts. (C) High magnification image of SIRT4 staining in MS of 12 weeks and 52 weeks. Scale bar = 50 μm. Data are expressed as mean ± SEM. Statistical analysis was carried out using analysis of variance, #P < 0.01 vs. control.
Mentions: SIRT4 immunoreactive cells were observed in the MS, OVLT and AHA regions (Figure 4). We observed SIRT4 protein localized mainly in neurons compared to glial cells in the POA (Figure 5A). SIRT4 co-localization with glial cells were observed in areas close to the third ventricle of the preoptic area whereas the vast majority of SIRT4 immunoreactivity was observed in neurons. There was no immunostaining when the antibody was preadsorbed with its corresponding antigen or when the antibody was excluded.

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