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Inhibition of Sirtuin 2 exerts neuroprotection in aging rats with increased neonatal iron intake.

Wang X, Wang M, Yang L, Bai J, Yan Z, Zhang Y, Liu Z - Neural Regen Res (2014)

Bottom Line: At present, very little is understood about the effect of neonatal iron intake on behavior in aging animals.Therefore, we hypothesized that increased neonatal iron intake would result in significant behavior abnormalities and striatal dopamine depletion during aging, and Sirtuin 2 contributes to the age-related neurotoxicity.Experimental findings suggest that increased neonatal iron intake may result in Parkinson's disease-like neurochemical and behavioral deficits with aging, and inhibition of Sirtuin 2 expression may be a neuroprotective measure in Parkinson's disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

ABSTRACT
Impaired iron homeostasis may cause damage to dopaminergic neurons and is critically involved in the pathogenesis of Parkinson's disease. At present, very little is understood about the effect of neonatal iron intake on behavior in aging animals. Therefore, we hypothesized that increased neonatal iron intake would result in significant behavior abnormalities and striatal dopamine depletion during aging, and Sirtuin 2 contributes to the age-related neurotoxicity. In the present study, we observed that neonatal iron intake (120 μg/g per day) during postnatal days 10-17 resulted in significant behavior abnormalities and striatal dopamine depletion in aging rats. Furthermore, after AK-7 (a selective Sirtuin 2 inhibitor) was injected into the substantia nigra at postnatal 540 days and 570 days (5 μg/side per day), striatal dopamine depletion was significantly diminished and behavior abnormality was improved in aging rats with neonatal iron intake. Experimental findings suggest that increased neonatal iron intake may result in Parkinson's disease-like neurochemical and behavioral deficits with aging, and inhibition of Sirtuin 2 expression may be a neuroprotective measure in Parkinson's disease.

No MeSH data available.


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Increased neonatal iron intake resulted in age-related behavior abnormalities.(A, B) Rotarod test in young (170 days old) and aging (615 days old) rats, respectively; (C, D) open field test in young (170 days old) and aging (615 days old) rats, respectively. Data are expressed as the mean ± SEM. (A, C) There were 20 young rats: 10 rats with neonatal iron intake and 10 vehicle-treated rats (B, D) and 20 aging rats: 10 rats with neonatal iron intake and 10 vehicle-treated rats. Differences were determined using the two-tailed Student's t-test for comparison between two groups and an analysis of variance and Bonferroni post hoc test for comparison between more than two groups. **P < 0.01, vs. aging rats treated with vehicle. rpm: Rotation/min.
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Figure 1: Increased neonatal iron intake resulted in age-related behavior abnormalities.(A, B) Rotarod test in young (170 days old) and aging (615 days old) rats, respectively; (C, D) open field test in young (170 days old) and aging (615 days old) rats, respectively. Data are expressed as the mean ± SEM. (A, C) There were 20 young rats: 10 rats with neonatal iron intake and 10 vehicle-treated rats (B, D) and 20 aging rats: 10 rats with neonatal iron intake and 10 vehicle-treated rats. Differences were determined using the two-tailed Student's t-test for comparison between two groups and an analysis of variance and Bonferroni post hoc test for comparison between more than two groups. **P < 0.01, vs. aging rats treated with vehicle. rpm: Rotation/min.

Mentions: The rotarod performance test and open field test were performed to evaluate the effect of neonatal iron intake on motor behavior in young and aging rats. As shown in Figure 1, neonatal iron intake had no impact on behavior changes in young rats compared with the vehicle-treated rats. However, significant decreases in latency and the number of crossings and rearings were observed in aging rats with neonatal intake of the same dose of iron compared with the vehicle-treated rats (P < 0.01; Figure 1). In agreement with the behavioral tests, neonatal iron intake did not result in significant striatal dopamine depletion in young rats compared with the vehicle-treated rats (Figure 2A). However, significantly decreased striatal dopamine content was observed in aging rats with neonatal iron intake compared with the vehicle-treated rats (P < 0.01; Figure 2A). No significant change in striatal serotonin level was observed in aging rats with neonatal iron intake compared with vehicle-treated rats (P > 0.05; Figure 2B).


Inhibition of Sirtuin 2 exerts neuroprotection in aging rats with increased neonatal iron intake.

Wang X, Wang M, Yang L, Bai J, Yan Z, Zhang Y, Liu Z - Neural Regen Res (2014)

Increased neonatal iron intake resulted in age-related behavior abnormalities.(A, B) Rotarod test in young (170 days old) and aging (615 days old) rats, respectively; (C, D) open field test in young (170 days old) and aging (615 days old) rats, respectively. Data are expressed as the mean ± SEM. (A, C) There were 20 young rats: 10 rats with neonatal iron intake and 10 vehicle-treated rats (B, D) and 20 aging rats: 10 rats with neonatal iron intake and 10 vehicle-treated rats. Differences were determined using the two-tailed Student's t-test for comparison between two groups and an analysis of variance and Bonferroni post hoc test for comparison between more than two groups. **P < 0.01, vs. aging rats treated with vehicle. rpm: Rotation/min.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4281432&req=5

Figure 1: Increased neonatal iron intake resulted in age-related behavior abnormalities.(A, B) Rotarod test in young (170 days old) and aging (615 days old) rats, respectively; (C, D) open field test in young (170 days old) and aging (615 days old) rats, respectively. Data are expressed as the mean ± SEM. (A, C) There were 20 young rats: 10 rats with neonatal iron intake and 10 vehicle-treated rats (B, D) and 20 aging rats: 10 rats with neonatal iron intake and 10 vehicle-treated rats. Differences were determined using the two-tailed Student's t-test for comparison between two groups and an analysis of variance and Bonferroni post hoc test for comparison between more than two groups. **P < 0.01, vs. aging rats treated with vehicle. rpm: Rotation/min.
Mentions: The rotarod performance test and open field test were performed to evaluate the effect of neonatal iron intake on motor behavior in young and aging rats. As shown in Figure 1, neonatal iron intake had no impact on behavior changes in young rats compared with the vehicle-treated rats. However, significant decreases in latency and the number of crossings and rearings were observed in aging rats with neonatal intake of the same dose of iron compared with the vehicle-treated rats (P < 0.01; Figure 1). In agreement with the behavioral tests, neonatal iron intake did not result in significant striatal dopamine depletion in young rats compared with the vehicle-treated rats (Figure 2A). However, significantly decreased striatal dopamine content was observed in aging rats with neonatal iron intake compared with the vehicle-treated rats (P < 0.01; Figure 2A). No significant change in striatal serotonin level was observed in aging rats with neonatal iron intake compared with vehicle-treated rats (P > 0.05; Figure 2B).

Bottom Line: At present, very little is understood about the effect of neonatal iron intake on behavior in aging animals.Therefore, we hypothesized that increased neonatal iron intake would result in significant behavior abnormalities and striatal dopamine depletion during aging, and Sirtuin 2 contributes to the age-related neurotoxicity.Experimental findings suggest that increased neonatal iron intake may result in Parkinson's disease-like neurochemical and behavioral deficits with aging, and inhibition of Sirtuin 2 expression may be a neuroprotective measure in Parkinson's disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

ABSTRACT
Impaired iron homeostasis may cause damage to dopaminergic neurons and is critically involved in the pathogenesis of Parkinson's disease. At present, very little is understood about the effect of neonatal iron intake on behavior in aging animals. Therefore, we hypothesized that increased neonatal iron intake would result in significant behavior abnormalities and striatal dopamine depletion during aging, and Sirtuin 2 contributes to the age-related neurotoxicity. In the present study, we observed that neonatal iron intake (120 μg/g per day) during postnatal days 10-17 resulted in significant behavior abnormalities and striatal dopamine depletion in aging rats. Furthermore, after AK-7 (a selective Sirtuin 2 inhibitor) was injected into the substantia nigra at postnatal 540 days and 570 days (5 μg/side per day), striatal dopamine depletion was significantly diminished and behavior abnormality was improved in aging rats with neonatal iron intake. Experimental findings suggest that increased neonatal iron intake may result in Parkinson's disease-like neurochemical and behavioral deficits with aging, and inhibition of Sirtuin 2 expression may be a neuroprotective measure in Parkinson's disease.

No MeSH data available.


Related in: MedlinePlus