[논문]Effect of Guibi-tang on Neuronal Apoptosis and Cognitive Impairment Induced by Beta Amyloid in Mice

Lee, Ju-Won; Cho, Dong-Guk; Cho, Woo-Sung; Ahn, Hyung-Gyu; Lee, Hyun-Joon; Shin, Jung-Won; Sohn, Nak-Won

doi:10.13048/jkm.14040

Effect of Guibi-tang on Neuronal Apoptosis and Cognitive Impairment Induced by Beta Amyloid in Mice 원문보기

Journal of Korean Medicine = 대한한의학회지, v.35 no.4, 2014년, pp.10 - 23

Lee, Ju-Won (Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung Hee University) , Cho, Dong-Guk (Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung Hee University) , Cho, Woo-Sung (Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung Hee University) , Ahn, Hyung-Gyu (Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung Hee University) , Lee, Hyun-Joon (Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung Hee University) , Shin, Jung-Won (Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung Hee University) , Sohn, Nak-Won (Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung Hee University)

Abstract ▼ AI-Helper

Objectives: This study evaluated the effects of Guibi-tang (GBT) on neuronal apoptosis and cognitive impairment induced by beta amyloid ($A{\beta}$), (1-42) injection in the hippocampus of ICR mice. Methods: $A{\beta}$ (1-42) was injected unilaterally into the lateral ventricle using a Hamilton syringe and micropump ($2{\mu}g/3{\mu}{\ell}$, $0.6{\mu}{\ell}/min$). Water extract of GBT was administered orally once a day (500 mg/kg) for 3 weeks after the $A{\beta}$ (1-42) injection. Acquisition of learning and retention of memory were tested using the Morris water maze. Neuronal damage and $A{\beta}$ accumulation in the hippocampus was observed using cresyl violet and Congo red staining. The anti-apoptotic effect of GBT was evaluated using TUNEL labeling in the hippocampus. Results: GBT significantly shortened the escape latencies during acquisition training trials. GBT significantly increased the number of target headings to the platform site, the swimming time spent in the target quadrant, and significantly shortened the time for the 1st target heading during the retention test trial. GBT significantly attenuated the reduction in thickness and number of CA1 neurons, and $A{\beta}$ accumulation in the hippocampus produced by $A{\beta}$ (1-42) injection. GBT significantly reduced the number of TUNEL-labeled neurons in the hippocampus. Conclusion: These results suggest that GBT improved cognitive impairment by reducing neuronal apoptosis and $A{\beta}$ accumulation in the hippocampus. GBT may be a beneficial herbal formulation in treating cognitive impairment including Alzheimer's disease.

주제어

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문제 정의

This study attempted to examine the impact of Guibi-tang in Alzheimer’s disease.

가설 설정

This showed that Aβ-induced brain tissue damage can be restored by Guibi-tang. We hypothesize that Guibi-tang may have a neuron protective effect by disrupting neuronal apoptosis.

제안 방법

Relative optical densities of Congo red, counting of the CA1 and DG neurons stained with cresyl violet and TUNEL-labeled cells were analyzed using ImageJ software (Ver. 1.44p, NIH, USA). The relative optical densities were measured in the CA1 and DG by the mean gray value on an inverted black-white binary image and were normalized to the value of the normal group.
The Morris water maze test was performed for 4 days. The acquisition training was performed for 3 days and the retention test on the 4th day. The apparatus consisted of a circular water pool 100 cm in diameter and 40 cm in height.
A solution of Guibi-tang or normal saline was given orally once daily for 21 days after surgery. The training trial was performed eight times a day for three days. Data are represented by mean ± SEM (n=12 in each group).
This study confirmed the pathological state of Aβ injected mouse by cresyl violet stain and Aβ accumulation in the hippocampus CA1 and DG region.
This study examined the effect of Guibi-tang administration on neuronal apoptosis in mice induced by intraventricular Aβ injection and the restoration of cognitive impairment caused by the neuronal damage using the Morris water maze.

대상 데이터

The Aβ and sham group received vehicle (normal saline) orally. A total of 36 mice were used.
Male C57BL/6 mice (25-28g, Nara Biotechnology, Korea) were used for this study. All animal protocols were approved by the Ethics Committee for the Care and Use of Laboratory Animals at Kyung Hee University.
The animals were housed in plastic cages at constant temperature (22±2°C) and humidity (55± 10%) with 12 h-12 h light-dark conditions.
The acquisition training was performed for 3 days and the retention test on the 4th day. The apparatus consisted of a circular water pool 100 cm in diameter and 40 cm in height. It was filled with 23 ± 1°C water with a depth of 28 cm and covered a black platform (10 cm in diameter).
The twelve crude herbs of GBT were purchased from Puremind Medicinal Herbs (Youngchen, Korea). A decoction of GBT was prepared in our laboratory from a mixture of chopped crude herbs (Table 1).

데이터처리

All data in this study are presented as means ± standard errors and were evaluated using Student’s t-test.
05 was used to indicate a significant difference. Differences between groups in the acquisition test were evaluated using one-way ANOVA.

이론/모형

Neuronal apoptosis was examined using TUNEL assay that stains DNA fragments as a result of cell death. TUNEL-labeled cells were rarely seen in the CA1 and DG regions of the sham group.

성능/효과

The GBT group showed improvement in advanced learning memory and cognition. Significant results during the training trials were mostly concentrated towards the tail end of the trials (14th, 16th, 20th, 23th, and 24th of 24 innings). The favorable effect of Guibi-tang was significant during the 2nd and 3rd day out of the three-day training period.

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