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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 proliferation rate, neuron lineage specification rate and survival rate of adult hippocampal neurogenesis.A) Proliferation rate, estimated by dividing the number of BrdU+ cells by the number of nestin+ cells. B) Neuron lineage specification rate, estimated by dividing the number of BrdU+DCX+ cells by the number of BrdU+ cells. C) Survival rate, estimated by dividing the number of BrdU+ cells, 2 h after BrdU injection, by the number of BrdU+ cells 1 month after BrdU injection.
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pone.0132152.g003: Effects of age and running exercise (Ex) on the proliferation rate, neuron lineage specification rate and survival rate of adult hippocampal neurogenesis.A) Proliferation rate, estimated by dividing the number of BrdU+ cells by the number of nestin+ cells. B) Neuron lineage specification rate, estimated by dividing the number of BrdU+DCX+ cells by the number of BrdU+ cells. C) Survival rate, estimated by dividing the number of BrdU+ cells, 2 h after BrdU injection, by the number of BrdU+ cells 1 month after BrdU injection.

Mentions: The number of newly proliferated cell is determined by the number of stem cells and the rate of stem cell proliferation. Therefore, we calculated the proliferation rate by dividing the number of BrdU+ cells by the number of nestin+ cells. The results showed that age (F = 42.0, d.f. = 4/61, p < 0.001), but not Ex (F = 0.3, d.f. = 1/61, p > 0.5), significantly changed the proliferation rate (Fig 3A). There was no interaction between the two factors (F = 0.1, d.f. = 4/61, p > 0.5). The proliferation rates of the 6-month-old and the 9-month-old mice were about 22% and 16% of the rate of the 3-month-old mice, respectively (Fig 3A).


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 proliferation rate, neuron lineage specification rate and survival rate of adult hippocampal neurogenesis.A) Proliferation rate, estimated by dividing the number of BrdU+ cells by the number of nestin+ cells. B) Neuron lineage specification rate, estimated by dividing the number of BrdU+DCX+ cells by the number of BrdU+ cells. C) Survival rate, estimated by dividing the number of BrdU+ cells, 2 h after BrdU injection, by the number of BrdU+ cells 1 month after BrdU injection.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0132152.g003: Effects of age and running exercise (Ex) on the proliferation rate, neuron lineage specification rate and survival rate of adult hippocampal neurogenesis.A) Proliferation rate, estimated by dividing the number of BrdU+ cells by the number of nestin+ cells. B) Neuron lineage specification rate, estimated by dividing the number of BrdU+DCX+ cells by the number of BrdU+ cells. C) Survival rate, estimated by dividing the number of BrdU+ cells, 2 h after BrdU injection, by the number of BrdU+ cells 1 month after BrdU injection.
Mentions: The number of newly proliferated cell is determined by the number of stem cells and the rate of stem cell proliferation. Therefore, we calculated the proliferation rate by dividing the number of BrdU+ cells by the number of nestin+ cells. The results showed that age (F = 42.0, d.f. = 4/61, p < 0.001), but not Ex (F = 0.3, d.f. = 1/61, p > 0.5), significantly changed the proliferation rate (Fig 3A). There was no interaction between the two factors (F = 0.1, d.f. = 4/61, p > 0.5). The proliferation rates of the 6-month-old and the 9-month-old mice were about 22% and 16% of the rate of the 3-month-old mice, respectively (Fig 3A).

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