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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 maturation of newborn neurons.A) Representative micrographs of DCX+ immature neurons in the dentate gyrus of the 9 and 21-month-old mice that received or did not receive Ex training. Examples of tracings (blue line) are used to measure the quality of dendrite of DCX+ immature neurons. Sed: sedentary group. Scale bar: 20 μm. B) Quantitative results of the number of branches of DCX+ dendrite. C) Quantitative results of the total length of DCX+ dendrite. **: Bonferroni post-hoc test: p < 0.01 vs. respective Sed group.
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pone.0132152.g004: Effects of age and running exercise (Ex) on the maturation of newborn neurons.A) Representative micrographs of DCX+ immature neurons in the dentate gyrus of the 9 and 21-month-old mice that received or did not receive Ex training. Examples of tracings (blue line) are used to measure the quality of dendrite of DCX+ immature neurons. Sed: sedentary group. Scale bar: 20 μm. B) Quantitative results of the number of branches of DCX+ dendrite. C) Quantitative results of the total length of DCX+ dendrite. **: Bonferroni post-hoc test: p < 0.01 vs. respective Sed group.

Mentions: We used the dendritic branch number and length of the DCX+ cells as an indication of newborn neuron maturation (Fig 4A). Because the dendritic arbors of the DCX+ cells substantially overlapped with neighboring DCX+ cells in young age mice, and thus interfered with analysis, we only compared the dendritic complexity of DCX+ cells in mice of 9- and 21-month-old groups. The number of dendritic branches was significantly affected by age (F = 6.4, d.f. = 1/16, p = 0.022) and Ex (F = 7.2, d.f. = 1/16, p = 0.016), with no interaction between these two factors (F = 1.8, d.f. = 1/16, p = 0.195) (Fig 4B). Similarly, the dendritic lengths were affected by age (F = 17.6, d.f. = 1/16, p < 0.001) and Ex (F = 12.5, d.f. = 1/16, p = 0.003). However, a significant interaction was observed between the two factors (F = 4.8, d.f. = 1/16, p = 0.044). Bonferroni post-hoc tests indicated that the dendritic lengths of the 9-month-old Ex mice were significantly longer than those of the 9-month-old Sed mice (Fig 4C).


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 maturation of newborn neurons.A) Representative micrographs of DCX+ immature neurons in the dentate gyrus of the 9 and 21-month-old mice that received or did not receive Ex training. Examples of tracings (blue line) are used to measure the quality of dendrite of DCX+ immature neurons. Sed: sedentary group. Scale bar: 20 μm. B) Quantitative results of the number of branches of DCX+ dendrite. C) Quantitative results of the total length of DCX+ dendrite. **: Bonferroni post-hoc test: p < 0.01 vs. respective Sed group.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4493040&req=5

pone.0132152.g004: Effects of age and running exercise (Ex) on the maturation of newborn neurons.A) Representative micrographs of DCX+ immature neurons in the dentate gyrus of the 9 and 21-month-old mice that received or did not receive Ex training. Examples of tracings (blue line) are used to measure the quality of dendrite of DCX+ immature neurons. Sed: sedentary group. Scale bar: 20 μm. B) Quantitative results of the number of branches of DCX+ dendrite. C) Quantitative results of the total length of DCX+ dendrite. **: Bonferroni post-hoc test: p < 0.01 vs. respective Sed group.
Mentions: We used the dendritic branch number and length of the DCX+ cells as an indication of newborn neuron maturation (Fig 4A). Because the dendritic arbors of the DCX+ cells substantially overlapped with neighboring DCX+ cells in young age mice, and thus interfered with analysis, we only compared the dendritic complexity of DCX+ cells in mice of 9- and 21-month-old groups. The number of dendritic branches was significantly affected by age (F = 6.4, d.f. = 1/16, p = 0.022) and Ex (F = 7.2, d.f. = 1/16, p = 0.016), with no interaction between these two factors (F = 1.8, d.f. = 1/16, p = 0.195) (Fig 4B). Similarly, the dendritic lengths were affected by age (F = 17.6, d.f. = 1/16, p < 0.001) and Ex (F = 12.5, d.f. = 1/16, p = 0.003). However, a significant interaction was observed between the two factors (F = 4.8, d.f. = 1/16, p = 0.044). Bonferroni post-hoc tests indicated that the dendritic lengths of the 9-month-old Ex mice were significantly longer than those of the 9-month-old Sed mice (Fig 4C).

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