트레드밀 운동이 streptozotocin 뇌실 처치로 유발된 알츠하이머 동물 모델 쥐의 신경염증과 신경세포사멸에 미치는 영향
The effect of treadmill exercise on neuroinflammation and neuronal cell death in intracerebroventricular streptozotocin-induced cognitive impairment in rats
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초록
본 연구는 뇌실(intracerebroventricular; ICV)에 streptozotocin(STZ) 처치로 유도된 알츠하이머 동물 모델 쥐를 대상으로 6주간의 트레드밀 운동이 별아교세포(astrocyte)에서의 염증반응, 해마 부위에서 염증관련 단백질과 신경세포의 사멸에 미치는 영향을 알아보았다. 실험동물은 Sham-CON(n=10), ICV-STZ CON(n=10), ICV-STZ TE(n=10)로 구분하였다. 트레드밀 운동은 하루에 30분, 주5일, 6주간 실시하였다. 먼저 수중미로검사에서 ICV-STZ CON 집단은 Sham-CON 집단에 비해 원형도피대를 찾는 시간과 거리가 유의하게 증가된 것으로 나타났다. 하지만 트레드밀 운동을 실시한 ICV-STZ TE 집단은 ICV-STZ CON 집단에 비해 원형도피대를 찾는 시간과 거리가 유의하게 감소된 것으로 나타났다. 별아교세포의 marker인 신경아교원섬유성산성단백질(glial fibrillary acidic protein; GFAP)의 경우 ICV-STZ CON 집단은 Sham-COM 집단에 비해 발현이 증가되었지만 ICV-STZ TE 집단은 ICV-STZ CON 집단에 비해 감소된 것으로 나타났다. 염증반응과 관련해서 ICV-STZ CON 집단은 Sham-CON 집단에 비해 TNF-α, IL-1β, Lipocalin-2, COX-2의 발현이 증가한 것으로 나타났지만 ICV-STZ TE 집단은 ICV-STZ CON 집단에 비해 감소된 것으로 나타났다. 신경세포의 사멸과 관련해서 ICV-STZ CON 집단은 Sham-CON 집단에 비해 caspase-3 와 Bax의 발현이 증가하였지만, Bcl-2는 감소한 것으로 나타나 신경세포의 사멸이 증가하는 것으로 나타났다. 하지만, 트레드밀 운동을 실시한 ICV-STZ TE 집단은 ICV-STZ CON 집단에 비해 신경세포의 사멸이 감소하는 것으로 나타났다. 따라서 본 연구에서 실시한 트레드밀 운동은 알츠하이머 동물 모델 쥐의 인지능력 저하의 개선, 염증반응의 감소 그리고 신경세포의 사멸을 억제하는 긍정적인 효과가 있는 것으로 나타났다. 즉 트레드밀 운동과 같은 유산소 운동은 알츠하이머 질환의 증상을 개선하기 위한 효과적인 대안으로 적용될 수 있다.
Abstract
The purpose of this study was to explore the effects of 6-week treadmill exercise on inflammation and neuronal cell death in the hippocampus of intracerebroventricular (ICV) streptozotocin (STZ)-injected Alzheimer's disease (AD) rats. The experimental animals were divided into Sham-CON group (n=10), ICV-STZ CON group (n=10) and ICV-STZ TE group (n=10). The treadmill exercise was conducted for 30 minutes a day, 5 days a week, for 6 weeks. First, in a water maze test, it turned out that the time and distance of finding an escape platform significantly increased in the ICV-STZ CON group as compared to those in the Sham-CON group. In contrast, it turned out that the time and distance of finding the escape platform significantly decreased in the ICV-STZ TE group in which the treadmill exercise was carried out as compared to those in the ICV-STZ CON group. The expression of marker of astrocytes, Glial Fibrillary Acidic Protein (GFAP) increased in the ICV-STZ CON group as compared to that in the Sham-COM group, but that in the ICV-STZ TE group decreased as compared to that in the ICV-STZ CON group. Regarding inflammatory reactions, it turned out that the expressions of TNF-α, IL-1β, Lipocalin-2 and COX-2 increased in the ICV-STZ CON group as compared to those of the Sham-CON group, but it turned out that those of the ICV-STZ TE group decreased as compared to those of the ICV-STZ CON group. Regarding neuronal cell deaths, the expressions of caspase-3 and Bax increased in the ICV-STZ CON group as compared to the Sham-CON group, but it turned out that the expression of Bcl-2 decreased, and the neuronal cell deaths increased. However, it turned out that the neuronal cell deaths decreased in the ICV-STZ TE group in which the treadmill exercise was carried out as compared to that in the ICV-STZ CON group. Therefore, it turned out that the treadmill exercise showed positive effects on improving cognitive ability by reducing inflammatory reactions and inhibiting neuronal cell deaths in the rats with AD. In other words, aerobic exercise like treadmill exercise can be applied as an effective alternative to improve symptoms of AD.
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