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Scolopendra subspinipes mutilans attenuates neuroinflammation in symptomatic hSOD1(G93A) mice.

Cai M, Choi SM, Song BK, Son I, Kim S, Yang EJ - J Neuroinflammation (2013)

Bottom Line: However, the mechanisms underlying the effects of SSM are currently unclear, even though SSM increases immune and antibiotic activity.We found that SSM treatment attenuated the loss of motor neurons and reduced the activation of microglial cells and astrocytes.Furthermore, we demonstrated that SSM administration in this animal model of ALS suppressed oxidative stress in the brainstem and spinal cord by 1.6- and 1.8-fold, respectively.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medial Research, Korea Institute of Oriental Medicine, 483 Expo-ro, Yuseong-gu, Daejeon 305-811, Republic of Korea. kscndl@hanmail.net.

ABSTRACT

Background: Amyotrophic lateral sclerosis (ALS) is a progressive, adult-onset neurodegenerative disorder characterized by selective motor neuron death in the spinal cord, brainstem, and motor cortex. Neuroinflammation is one of several pathological causes of degenerating motor neurons and is induced by activated microglial cells and astrocytes in ALS.Scolopendra subspinipes mutilans (SSM) is utilized in traditional Chinese and Korean medicine for the treatment of a variety of diseases, such as cancer, apoplexy, and epilepsy. However, the mechanisms underlying the effects of SSM are currently unclear, even though SSM increases immune and antibiotic activity.

Methods: To determine the effects of SSM on symptomatic hSOD1G93A transgenic mice, SSM (2.5 μℓ/g) was injected bilaterally at the Zusanli (ST36) acupoint three times per week for two weeks. The effects of SSM treatment on anti-neuroinflammation in the brainstem and spinal cord of hSOD1G93A mice were assessed via Nissl and Fluoro-Jade B (FJB) staining, and immunohistochemistry using Iba-1, CD14, HO1, and NQO1 proteins was evaluated by Western blotting.

Results: In this study, we investigated whether SSM affects neuroinflammation in the spinal cord of symptomatic hSOD1G93A transgenic mice. We found that SSM treatment attenuated the loss of motor neurons and reduced the activation of microglial cells and astrocytes. Furthermore, we demonstrated that SSM administration in this animal model of ALS suppressed oxidative stress in the brainstem and spinal cord by 1.6- and 1.8-fold, respectively.

Conclusions: Our findings suggest that SSM, which has previously been used in complementary and alternative medicine (CAM), might also be considered as an anti-neuroinflammatory therapy for neurodegenerative diseases.

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SSM treatment reduces the expression of Iba-1 and GFAP in 113-day-old hSOD1G93A mice. Representative photomicrographs of Iba-1 (A) and GFAP (B) staining in the lumbar spinal cord. Each column on the right depicts a magnified image of the rectangular region of the corresponding image in the left column. (C) Representative Western blot showing the activation of microglia using an Iba-1 antibody and the detection of astrocytes with a GFAP antibody in the brainstems and spinal cords of hSOD1G93A mice. (D) Quantitative analysis of the levels of Iba1/tubulin and GFAP/tubulin, respectively. The data are presented as the means ± SEM (N = 6 animals/genotype). Statistical significance was assessed via t-test. **P < 0.01 compared to the saline-treated group. SSM: Scolopendra subspinipes mutilans, BS: brainstem, SP: spinal cord.
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Figure 2: SSM treatment reduces the expression of Iba-1 and GFAP in 113-day-old hSOD1G93A mice. Representative photomicrographs of Iba-1 (A) and GFAP (B) staining in the lumbar spinal cord. Each column on the right depicts a magnified image of the rectangular region of the corresponding image in the left column. (C) Representative Western blot showing the activation of microglia using an Iba-1 antibody and the detection of astrocytes with a GFAP antibody in the brainstems and spinal cords of hSOD1G93A mice. (D) Quantitative analysis of the levels of Iba1/tubulin and GFAP/tubulin, respectively. The data are presented as the means ± SEM (N = 6 animals/genotype). Statistical significance was assessed via t-test. **P < 0.01 compared to the saline-treated group. SSM: Scolopendra subspinipes mutilans, BS: brainstem, SP: spinal cord.

Mentions: Neuroinflammation caused by activated microglial cells and astrocytes is the hallmark pathological feature of ALS in animals and patients [5-7,27,28]. To investigate the effects of SSM treatment on microglial cells and astrocytes in the spinal cords and brainstems of symptomatic hSOD1G93A transgenic mice, we examined the expression of Iba-1 to visualize microglial cells and the expression of GFAP to visualize astrocytes in the brainstems and spinal cords of SSM-treated hSOD1G93A transgenic mice and age-matched control mice. As shown in Figure 2A, SSM administration markedly reduced the massive activation of microglial cells (Iba-1-positive cells) and astrocytes (GFAP-stained cells) observed in the ventral horn of the lumbar spinal cord. In addition, biochemical analysis confirmed that the expression of Iba-1 was significantly reduced by 3.3- and 2.1-fold in the brainstem and spinal cord, respectively, compared to control mice (Figure 2C-D). Through Western blotting (Figure 2C- D), we found that, compared to age-matched control mice, the level of GFAP expression was decreased by 1.5- and 1.2-fold in the brainstems and spinal cords, respectively, of SSM-treated hSOD1G93A transgenic mice.


Scolopendra subspinipes mutilans attenuates neuroinflammation in symptomatic hSOD1(G93A) mice.

Cai M, Choi SM, Song BK, Son I, Kim S, Yang EJ - J Neuroinflammation (2013)

SSM treatment reduces the expression of Iba-1 and GFAP in 113-day-old hSOD1G93A mice. Representative photomicrographs of Iba-1 (A) and GFAP (B) staining in the lumbar spinal cord. Each column on the right depicts a magnified image of the rectangular region of the corresponding image in the left column. (C) Representative Western blot showing the activation of microglia using an Iba-1 antibody and the detection of astrocytes with a GFAP antibody in the brainstems and spinal cords of hSOD1G93A mice. (D) Quantitative analysis of the levels of Iba1/tubulin and GFAP/tubulin, respectively. The data are presented as the means ± SEM (N = 6 animals/genotype). Statistical significance was assessed via t-test. **P < 0.01 compared to the saline-treated group. SSM: Scolopendra subspinipes mutilans, BS: brainstem, SP: spinal cord.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4231348&req=5

Figure 2: SSM treatment reduces the expression of Iba-1 and GFAP in 113-day-old hSOD1G93A mice. Representative photomicrographs of Iba-1 (A) and GFAP (B) staining in the lumbar spinal cord. Each column on the right depicts a magnified image of the rectangular region of the corresponding image in the left column. (C) Representative Western blot showing the activation of microglia using an Iba-1 antibody and the detection of astrocytes with a GFAP antibody in the brainstems and spinal cords of hSOD1G93A mice. (D) Quantitative analysis of the levels of Iba1/tubulin and GFAP/tubulin, respectively. The data are presented as the means ± SEM (N = 6 animals/genotype). Statistical significance was assessed via t-test. **P < 0.01 compared to the saline-treated group. SSM: Scolopendra subspinipes mutilans, BS: brainstem, SP: spinal cord.
Mentions: Neuroinflammation caused by activated microglial cells and astrocytes is the hallmark pathological feature of ALS in animals and patients [5-7,27,28]. To investigate the effects of SSM treatment on microglial cells and astrocytes in the spinal cords and brainstems of symptomatic hSOD1G93A transgenic mice, we examined the expression of Iba-1 to visualize microglial cells and the expression of GFAP to visualize astrocytes in the brainstems and spinal cords of SSM-treated hSOD1G93A transgenic mice and age-matched control mice. As shown in Figure 2A, SSM administration markedly reduced the massive activation of microglial cells (Iba-1-positive cells) and astrocytes (GFAP-stained cells) observed in the ventral horn of the lumbar spinal cord. In addition, biochemical analysis confirmed that the expression of Iba-1 was significantly reduced by 3.3- and 2.1-fold in the brainstem and spinal cord, respectively, compared to control mice (Figure 2C-D). Through Western blotting (Figure 2C- D), we found that, compared to age-matched control mice, the level of GFAP expression was decreased by 1.5- and 1.2-fold in the brainstems and spinal cords, respectively, of SSM-treated hSOD1G93A transgenic mice.

Bottom Line: However, the mechanisms underlying the effects of SSM are currently unclear, even though SSM increases immune and antibiotic activity.We found that SSM treatment attenuated the loss of motor neurons and reduced the activation of microglial cells and astrocytes.Furthermore, we demonstrated that SSM administration in this animal model of ALS suppressed oxidative stress in the brainstem and spinal cord by 1.6- and 1.8-fold, respectively.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medial Research, Korea Institute of Oriental Medicine, 483 Expo-ro, Yuseong-gu, Daejeon 305-811, Republic of Korea. kscndl@hanmail.net.

ABSTRACT

Background: Amyotrophic lateral sclerosis (ALS) is a progressive, adult-onset neurodegenerative disorder characterized by selective motor neuron death in the spinal cord, brainstem, and motor cortex. Neuroinflammation is one of several pathological causes of degenerating motor neurons and is induced by activated microglial cells and astrocytes in ALS.Scolopendra subspinipes mutilans (SSM) is utilized in traditional Chinese and Korean medicine for the treatment of a variety of diseases, such as cancer, apoplexy, and epilepsy. However, the mechanisms underlying the effects of SSM are currently unclear, even though SSM increases immune and antibiotic activity.

Methods: To determine the effects of SSM on symptomatic hSOD1G93A transgenic mice, SSM (2.5 μℓ/g) was injected bilaterally at the Zusanli (ST36) acupoint three times per week for two weeks. The effects of SSM treatment on anti-neuroinflammation in the brainstem and spinal cord of hSOD1G93A mice were assessed via Nissl and Fluoro-Jade B (FJB) staining, and immunohistochemistry using Iba-1, CD14, HO1, and NQO1 proteins was evaluated by Western blotting.

Results: In this study, we investigated whether SSM affects neuroinflammation in the spinal cord of symptomatic hSOD1G93A transgenic mice. We found that SSM treatment attenuated the loss of motor neurons and reduced the activation of microglial cells and astrocytes. Furthermore, we demonstrated that SSM administration in this animal model of ALS suppressed oxidative stress in the brainstem and spinal cord by 1.6- and 1.8-fold, respectively.

Conclusions: Our findings suggest that SSM, which has previously been used in complementary and alternative medicine (CAM), might also be considered as an anti-neuroinflammatory therapy for neurodegenerative diseases.

Show MeSH
Related in: MedlinePlus