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系統識別號 U0026-2504201715425900
論文名稱(中文) 跑步運動誘發之腦源性神經滋養因子與神經活化的關連
論文名稱(英文) Study the relationship between running-induced neuronal activation and BDNF expression
校院名稱 成功大學
系所名稱(中) 細胞生物與解剖學研究所
系所名稱(英) Institute of Cell Biology and Anatomy
學年度 105
學期 2
出版年 106
研究生(中文) 黃婉寧
研究生(英文) Wan-Ning Huang
學號 T96031012
學位類別 碩士
語文別 英文
論文頁數 55頁
口試委員 指導教授-郭余民
口試委員-司君一
口試委員-許鍾瑜
中文關鍵字 運動  腦源神經滋養因子  神經活性  老年 
英文關鍵字 Aging  Exercise  Neuronal activity  BDNF 
學科別分類
中文摘要 記憶喪失威脅老齡人口健康甚鉅,海馬回為研究老化相關記憶缺失的重要
腦區,因其為早期即表現老化徵兆的腦區之一。規律的運動可多方面地改善大腦功能,其中包括緩和因老化導致的記憶損傷。腦源性神經滋養因子訊息的活化則在運動改善腦功能中扮演重要角色。然而,運動是透過何機制來誘發腦源性神經滋養因子的表現量,至今仍不非常清楚。已知腦源性神經滋養因子可因神經元活化而釋放,而跑步機運動則可誘發小鼠海馬回之神經元活化。綜合上述,我假設跑步運動是藉由活化海馬回神經元,來誘導腦源性神經滋養因子的表現。我會先探討神經元活化對運動所誘發腦源性神經滋養因子表現的關係,接著再探究年輕與年老的小鼠,對此二參數之影響。我以 cFOS 染色來標定活化的神經元,並以螢光染色法呈現腦源性神經滋養因子的表現。結果顯示,3個月年輕小鼠在經歷一小時的急性跑步機運動後,其海馬回中各個區域(dentate gyrus,CA2/3 和 CA1)被 cFOS 標定的神經元數目顯著增加,其腦源性神經滋養因子的螢光強度也增加。以河魨毒素(tetrodotoxin)抑制海馬回神經元之活性,則會降低運動所增加之腦源性神經滋養因子的螢光強度。此結果顯示,運動所
增加腦源性神經滋養因子的表現,是先透過活化該區域之神經元。以相同的方法比較長期(4 周)運動之訓練效果發現,老年(23 個月)鼠的海馬回中被 cFOS 標定的神經元數目和腦源性神經滋養因子的螢光強度都有增加,但是程度比年輕(3 個月)小鼠低。總結本研究,跑步運動可於海馬回內,藉由活化神經元來增加腦源性神經滋養因子的表現量。此一效果在年輕小鼠更為顯著,可能是因為相較於老年小鼠,年輕小鼠對運動所帶來的神經傳入刺激更大的緣故。
英文摘要 Memory loss emerges as a great threat to the elderly population. The hippocampus is an important structure for investigating the aging-associated memory deficits, because it is one of the region showing the earliest age-related
changes. Regular exercise multi-dimensionally improves the brain functions, including alleviating the age-related memory impairments. The brain-derived neurotrophic factor (BDNF) signaling pathway are critical in the exercise-induced benefits. However, the mechanisms underlying how exercise upregulates the BDNF expression in the brain remains unclear. It has been demonstrated that BDNF can be
released from activated neurons, and treadmill running induces neuronal activation in the hippocampi of mice. Accordingly, I hypothesized that exercise upregulates
the BDNF expression in the hippocampus by inducing local neuronal activation. I first investigated the role of neuronal activation in the exercise-induced upregulation of BDNF. Then, the effects of age on exercise-induced responses were also determined. The activity of neurons was determined by the immunoreactivity of cFOS, and the expression level of BDNF was measured by the intensity of
immunofluorescent staining. The results showed that a 1-h acute treadmill running concurrently increased the numbers of cFOS-positive neuron and the intensities of BDNF-positive signal in the hippocampal regions (dentate gyrus, CA2/3 and CA1) of 3-month-old mice. Blocking the neuronal activation by intra-hippocampus injection of tetrodotoxin decreased the exercise-induced intensities of BDNF-positive signal in the hippocampi. These results suggest that
exercise-induced upregulation of BDNF is due to exercise-induced local neuronal activation. I also found that chronic (4-week) treadmill running increased the levels
of neuronal activation and BDNF expression in the hippocampi of aged (23-month-old) mice. However, these changes were weaker than those in the young (3-month-old) mice. In conclusion, this study suggests that exercise upregulates the hippocampal BDNF expression by increasing local neuronal activity. These effects are more pronounced in the young mice than the aged mice, probably due to larger exercise-induced afferent nerve stimulation in the young mice.
論文目次 Abstract in Chinese........... I

Abstract............. Ⅱ
Contents............ Ⅳ
List of Figures............ Ⅵ
I. Introduction........... 1
1. Exercise and Brain Structures and Functions.... 1
2. Brain-Derived Neurotrophic Factor (BDNF), Brain Health and
Exercise........... 1
3. Neuronal Activity and Exercise...... 2
4. Aging............ 3
II. Purpose and Specific Aims........ 4
III. Materials And Methods......... 6
1. Animals.......... 6
2. Treadmill running protocol........ 6
3. Intra-hippocampal delivery of TTX..... 7
4. Brain preparation......... 8
5. Immunohistochemistry........ 8


V

6. Immunofluorescence........ 9
7. Statistical analysis........ 10
IV. Results........... 11
1. Treadmill exercise training concurrently induces neuronal activation
and BDNF expression in the hippocampus of mice.... 11
2. Blocking the exercise-induced neural activation abolishes the
exercise-induced BDNF expression..... 11
3. Exercise induces the hippocampal neuronal activation and BDNF
expression in both young and aged mice which have been exposed to a
long-term exercise training....... 13
4. The exercise-induced hippocampal neuronal activation and BDNF
expression are more augmented in young mice than those in aged
mice............ 15
V. Discussion........... 16
VI. References........... 20
VII. Figures............ 25






VI

List of Figures Figure 1.
The effects of acute treadmill exercise on the c-Fos expression in the
hippocampus........... 25
Figure 2.
The effects of acute treadmill exercise on the BDNF expression in the
hippocampus........... 27
Figure 3.
Expression of c-Fos in the hippocampus after TTX injection.. 29
Figure 4.
The effects of TTX infusion on the exercise-induced c-Fos expression in the
CA1............. 30
Figure 5.
The effects of TTX infusion on the exercise-induced BDNF expression in the
CA1............. 32
Figure 6.
The effects of TTX infusion on the exercise-induced c-Fos expression in the
CA2/3............ 34
Figure 7.
The effects of TTX infusion on the exercise-induced BDNF expression in the
CA2/3............. 36
Figure 8.
Expression of c-Fos in the DG after TTX injection.... 38



VII

Figure 9.
Expression of BDNF in the DG after TTX injection.... 40
Figure 10.
Effect of long-term exercise on density of c-Fos+ cells in different time of
treadmill running in CA1 of young and aging mice..... 42
Figure 11.
Effect of long-term exercise on intensity of BDNF+ cells in different time of
treadmill running in CA1 of young and aging mice.... 44
Figure 12.
Effect of long-term exercise on density of c-Fos+ cells in different time of
treadmill running in CA2/3 of young and aging mice... 46
Figure 13.
Effect of long-term exercise on intensity of BDNF+ cells in different time of
treadmill running in CA2/3 of young and aging mice... 48
Figure 14.
Effect of long-term exercise on density of c-Fos+ cells in different time of
treadmill running in DG of young and aging mice.... 50
Figure 15.
Effect of long-term exercise on intensity of BDNF+ cells in different time of
treadmill running in DG of young and aging mice.... 52
Figure 16.
Effect of long-term exercise on c-Fos+ cells and BDNF+ cells in different
time of treadmill running in CA1, CA3 and DG of young mice compare with
aging mice........... 54
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