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Aging and Exercise Affect Hippocampal Neurogenesis via Different Mechanisms.

Yang TT, Lo CP, Tsai PS, Wu SY, Wang TF, Chen YW, Jiang-Shieh YF, Kuo YM - PLoS ONE (2015)

Bottom Line: Aging greatly reduced newborn neuron maturation, while Ex potently enhanced it.In conclusion, age-associated decline of hippocampal neurogenesis is mainly caused by reduction of NSC proliferation.Hence, the effect of Ex on the rate of hippocampal neurogenesis during aging is limited, but Ex does enhance the maturation of newborn neurons.

View Article: PubMed Central - PubMed

Affiliation: School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung, Taiwan.

ABSTRACT
The rate of neurogenesis is determined by 1) the number of neural stem/progenitor cells (NSCs), 2) proliferation of NSCs, 3) neuron lineage specification, and 4) survival rate of the newborn neurons. Aging lowers the rate of hippocampal neurogenesis, while exercise (Ex) increases this rate. However, it remains unclear which of the determinants are affected by aging and Ex. We characterized the four determinants in different age groups (3, 6, 9, 12, 21 months) of mice that either received one month of Ex training or remained sedentary. Bromodeoxyuridine (BrdU) was injected two hours before sacrificing the mice to label the proliferating cells. The results showed that the number of newborn neurons massively decreased (>95%) by the time the mice reached nine months of age. The number of NSC was mildly reduced during aging, while Ex delayed such decline. The proliferation rates were greatly decreased by the time the mice were 9-month-old and Ex could not improve the rates. The rates of neuron specification were decreased during aging, while Ex increased the rates. The survival rate was not affected by age or Ex. Aging greatly reduced newborn neuron maturation, while Ex potently enhanced it. In conclusion, age-associated decline of hippocampal neurogenesis is mainly caused by reduction of NSC proliferation. Although Ex increases the NSC number and neuron specification rates, it doesn't restore the massive decline of NSC proliferation rate. Hence, the effect of Ex on the rate of hippocampal neurogenesis during aging is limited, but Ex does enhance the maturation of newborn neurons.

No MeSH data available.


Related in: MedlinePlus

Effects of age and running exercise (Ex) on the number of newly proliferated cells and that of immature neurons in the adult hippocampus.Representative micrographs of BrdU+ newborn cells (A), DCX+ immature neurons (D) and BrdU+DCX+ newborn neurons (G) in the hippocampal dentate gyrus of mice at 3, 9 and 21 months of age. Sed: sedentary group. Bar = 100 μm. Enlarged micrographs of BrdU+ cells (B), DCX+ immature neurons (E) and BrdU+DCX+ newborn neurons (H) are presented to illustrate the detail locations of these cells. Bar = 20 μm. SGZ: subgranular zone; GCL: granular cell layer; MoL: molecular layer. Quantitative analyses of BrdU+ cells (C), DCX+ cells (F) and BrdU+DCX+ cells (I) in dentate gyrus of mice with different ages. ***: Bonferroni post-hoc test: p < 0.001 vs. respective Sed group.
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pone.0132152.g001: Effects of age and running exercise (Ex) on the number of newly proliferated cells and that of immature neurons in the adult hippocampus.Representative micrographs of BrdU+ newborn cells (A), DCX+ immature neurons (D) and BrdU+DCX+ newborn neurons (G) in the hippocampal dentate gyrus of mice at 3, 9 and 21 months of age. Sed: sedentary group. Bar = 100 μm. Enlarged micrographs of BrdU+ cells (B), DCX+ immature neurons (E) and BrdU+DCX+ newborn neurons (H) are presented to illustrate the detail locations of these cells. Bar = 20 μm. SGZ: subgranular zone; GCL: granular cell layer; MoL: molecular layer. Quantitative analyses of BrdU+ cells (C), DCX+ cells (F) and BrdU+DCX+ cells (I) in dentate gyrus of mice with different ages. ***: Bonferroni post-hoc test: p < 0.001 vs. respective Sed group.

Mentions: To estimate the rate of hippocampal neurogenesis during aging, we counted the BrdU+DCX+ cell number in the hippocampal dentate gyrus of mice at the ages of 3, 6, 9, 12 and 21 months. Before obtaining the number of BrdU+DCX+ cells, we collected the number of BrdU+ cells and that of DCX+ cells first. We injected mice with BrdU to label the newly proliferated cells one day after completion of the 5-week Ex training program. Because the half-life of BrdU is about two hours [17], mice were killed 2 h after injection. As shown in Fig 1A, BrdU+ cells mainly resided in the subgranular zone of the dentate gyrus. The BrdU+ cells were frequently clustered together, indicating that they might be derived from the same ancestor NSC (Fig 1B). Two-way ANOVA results showed that both age (F = 97.0, d.f. = 4/80, p < 0.001) and Ex (F = 6.4, d.f. = 1/80, p = 0.013) altered the number of BrdU+ cells, without interaction between these two factors (F = 0.4, d.f. = 4/80, p > 0.5)(Fig 1C).


Aging and Exercise Affect Hippocampal Neurogenesis via Different Mechanisms.

Yang TT, Lo CP, Tsai PS, Wu SY, Wang TF, Chen YW, Jiang-Shieh YF, Kuo YM - PLoS ONE (2015)

Effects of age and running exercise (Ex) on the number of newly proliferated cells and that of immature neurons in the adult hippocampus.Representative micrographs of BrdU+ newborn cells (A), DCX+ immature neurons (D) and BrdU+DCX+ newborn neurons (G) in the hippocampal dentate gyrus of mice at 3, 9 and 21 months of age. Sed: sedentary group. Bar = 100 μm. Enlarged micrographs of BrdU+ cells (B), DCX+ immature neurons (E) and BrdU+DCX+ newborn neurons (H) are presented to illustrate the detail locations of these cells. Bar = 20 μm. SGZ: subgranular zone; GCL: granular cell layer; MoL: molecular layer. Quantitative analyses of BrdU+ cells (C), DCX+ cells (F) and BrdU+DCX+ cells (I) in dentate gyrus of mice with different ages. ***: Bonferroni post-hoc test: p < 0.001 vs. respective Sed group.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493040&req=5

pone.0132152.g001: Effects of age and running exercise (Ex) on the number of newly proliferated cells and that of immature neurons in the adult hippocampus.Representative micrographs of BrdU+ newborn cells (A), DCX+ immature neurons (D) and BrdU+DCX+ newborn neurons (G) in the hippocampal dentate gyrus of mice at 3, 9 and 21 months of age. Sed: sedentary group. Bar = 100 μm. Enlarged micrographs of BrdU+ cells (B), DCX+ immature neurons (E) and BrdU+DCX+ newborn neurons (H) are presented to illustrate the detail locations of these cells. Bar = 20 μm. SGZ: subgranular zone; GCL: granular cell layer; MoL: molecular layer. Quantitative analyses of BrdU+ cells (C), DCX+ cells (F) and BrdU+DCX+ cells (I) in dentate gyrus of mice with different ages. ***: Bonferroni post-hoc test: p < 0.001 vs. respective Sed group.
Mentions: To estimate the rate of hippocampal neurogenesis during aging, we counted the BrdU+DCX+ cell number in the hippocampal dentate gyrus of mice at the ages of 3, 6, 9, 12 and 21 months. Before obtaining the number of BrdU+DCX+ cells, we collected the number of BrdU+ cells and that of DCX+ cells first. We injected mice with BrdU to label the newly proliferated cells one day after completion of the 5-week Ex training program. Because the half-life of BrdU is about two hours [17], mice were killed 2 h after injection. As shown in Fig 1A, BrdU+ cells mainly resided in the subgranular zone of the dentate gyrus. The BrdU+ cells were frequently clustered together, indicating that they might be derived from the same ancestor NSC (Fig 1B). Two-way ANOVA results showed that both age (F = 97.0, d.f. = 4/80, p < 0.001) and Ex (F = 6.4, d.f. = 1/80, p = 0.013) altered the number of BrdU+ cells, without interaction between these two factors (F = 0.4, d.f. = 4/80, p > 0.5)(Fig 1C).

Bottom Line: Aging greatly reduced newborn neuron maturation, while Ex potently enhanced it.In conclusion, age-associated decline of hippocampal neurogenesis is mainly caused by reduction of NSC proliferation.Hence, the effect of Ex on the rate of hippocampal neurogenesis during aging is limited, but Ex does enhance the maturation of newborn neurons.

View Article: PubMed Central - PubMed

Affiliation: School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung, Taiwan.

ABSTRACT
The rate of neurogenesis is determined by 1) the number of neural stem/progenitor cells (NSCs), 2) proliferation of NSCs, 3) neuron lineage specification, and 4) survival rate of the newborn neurons. Aging lowers the rate of hippocampal neurogenesis, while exercise (Ex) increases this rate. However, it remains unclear which of the determinants are affected by aging and Ex. We characterized the four determinants in different age groups (3, 6, 9, 12, 21 months) of mice that either received one month of Ex training or remained sedentary. Bromodeoxyuridine (BrdU) was injected two hours before sacrificing the mice to label the proliferating cells. The results showed that the number of newborn neurons massively decreased (>95%) by the time the mice reached nine months of age. The number of NSC was mildly reduced during aging, while Ex delayed such decline. The proliferation rates were greatly decreased by the time the mice were 9-month-old and Ex could not improve the rates. The rates of neuron specification were decreased during aging, while Ex increased the rates. The survival rate was not affected by age or Ex. Aging greatly reduced newborn neuron maturation, while Ex potently enhanced it. In conclusion, age-associated decline of hippocampal neurogenesis is mainly caused by reduction of NSC proliferation. Although Ex increases the NSC number and neuron specification rates, it doesn't restore the massive decline of NSC proliferation rate. Hence, the effect of Ex on the rate of hippocampal neurogenesis during aging is limited, but Ex does enhance the maturation of newborn neurons.

No MeSH data available.


Related in: MedlinePlus