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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 neural stem/precursor cells (NSCs) in the adult hippocampus.A) Representative micrographs of nestin+ cells in the hippocampal dentate gyrus of mice at 3, 9 and 21 months of age. Sed: sedentary group. Scale bar: 100 μm. B) Quantitative analyses of nestin+ cells in the dentate gyrus of mice with different ages.
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pone.0132152.g002: Effects of age and running exercise (Ex) on the number of neural stem/precursor cells (NSCs) in the adult hippocampus.A) Representative micrographs of nestin+ cells in the hippocampal dentate gyrus of mice at 3, 9 and 21 months of age. Sed: sedentary group. Scale bar: 100 μm. B) Quantitative analyses of nestin+ cells in the dentate gyrus of mice with different ages.

Mentions: The effects of aging and those of Ex on NSCs were determined by counting the nestin+ cell number in the hippocampal dentate gyrus of mice at the ages of 3, 6, 9, 12 and 21 months (Fig 2A). Two-way ANOVA revealed that both age (F = 4.5, d.f. = 4/44, p = 0.004) and Ex (F = 4.5, d.f. = 1/44, p = 0.040) altered the number of NSC, without significant interaction between these two factors (F = 0.2, d.f. = 4/44, p > 0.5)(Fig 2B). However, post-hoc analysis indicated that the age effect was mainly contributed by the 3-month-old group, while the number of NSC remained unchanged in other older age groups (F = 1.4, d.f. = 3/29, p = 0.276). Using 3-month-old mice group as a reference point, the decline of NSCs by the age of 9-month was insignificant, where the measured value was slightly more than 10% (Fig 2B).


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 neural stem/precursor cells (NSCs) in the adult hippocampus.A) Representative micrographs of nestin+ cells in the hippocampal dentate gyrus of mice at 3, 9 and 21 months of age. Sed: sedentary group. Scale bar: 100 μm. B) Quantitative analyses of nestin+ cells in the dentate gyrus of mice with different ages.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0132152.g002: Effects of age and running exercise (Ex) on the number of neural stem/precursor cells (NSCs) in the adult hippocampus.A) Representative micrographs of nestin+ cells in the hippocampal dentate gyrus of mice at 3, 9 and 21 months of age. Sed: sedentary group. Scale bar: 100 μm. B) Quantitative analyses of nestin+ cells in the dentate gyrus of mice with different ages.
Mentions: The effects of aging and those of Ex on NSCs were determined by counting the nestin+ cell number in the hippocampal dentate gyrus of mice at the ages of 3, 6, 9, 12 and 21 months (Fig 2A). Two-way ANOVA revealed that both age (F = 4.5, d.f. = 4/44, p = 0.004) and Ex (F = 4.5, d.f. = 1/44, p = 0.040) altered the number of NSC, without significant interaction between these two factors (F = 0.2, d.f. = 4/44, p > 0.5)(Fig 2B). However, post-hoc analysis indicated that the age effect was mainly contributed by the 3-month-old group, while the number of NSC remained unchanged in other older age groups (F = 1.4, d.f. = 3/29, p = 0.276). Using 3-month-old mice group as a reference point, the decline of NSCs by the age of 9-month was insignificant, where the measured value was slightly more than 10% (Fig 2B).

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