Meteorin is upregulated in reactive astrocytes and functions as a negative feedback effector in reactive gliosis

LEE, HYE SHIN,LEE, SOON-HEE,CHA, JONG-HO,SEO, JI HAE,AHN, BUM JU,KIM, KYU-WON SPANDIDOS PUBLICATIONS 2015 MOLECULAR MEDICINE REPORTS Vol.12 No.2

<P>Reactive gliosis is a glial response to a wide range of central nervous system insults, which results in cellular and molecular changes to resting glial cells. Despite its fundamental effect on neuropathologies, the identification and characterization of the molecular mechanisms underlying this process remain to be fully elucidated. The aim of the present study was to analyze the expression profile and functions of the astrocytic neurotrophic factor, meteorin, in the progression of reactive gliosis. A mouse model of photothrombotic ischemia, and a primary astrocyte culture were used in the present study. Reverse transcription quantitative polymerase chain reaction, western blotting and immunofluorescence staining were performed to examine the expression levels of meteorin and reactive gliosis markers. Increased expression levels of meteorin were observed in reactive astrocytes in a photothrombotic ischemia mouse model, as well as in cultured astrocytes, which were stimulated by transforming growth factor-β1. Exogenous treatment of the astrocytes with meteorin did not induce janus kinase-signal transducer and activator of transcription 3 signaling, however, silencing the expression of meteorin in the astrocytes resulted in an upregulation of reactive astrocyte markers, including glial fibrillary acidic protein and S100β, indicating that endogenous meteorin is required for the maintenance of astrocytic homeostasis. These results suggested a novel role for meteorin as a negative feedback effector in reactive gliosis.</P>

목단피(牧丹皮)가 손상된 성상신경세포의 CD81 및 GFAP의 발현에 미치는 영향

문성진,성기문,임진영,송봉근,Moon, Sung-Jin,Seon, Ki-Moon,Lim, Jin-Young,Song, Bong-Keun 대한한방내과학회 2009 大韓韓方內科學會誌 Vol.30 No.1

Object : In conditions of brain infarction, irreversible axon damage occurs in the central nerve system (CNS), because gliosis makes physical and mechanical barriers. If gliosis formation could be suppressed, irreversible axon damage would be reduced. This could mean that an injured CNS could be regenerated. CD81 and GFAP have close relationships to gliosis. The increase in glial cells at CNS injury gives rise to the expression of CD81 and GFAP. CD81 was postulated to play a central role in the process of CNS scar formation. Method : In this study, the author investigated the effect of the water extract of the Moutan Radicis Cortex on regulation of CD81 and GFAP expression in injured CNS cells. MTT assay was used to examine cell viability, while RT-PCR and ELISA methods were carried out to measure the expression of CD81 and GFAP in the astrocyte. Results : We observed that water extract of the Moutan Radicis Cortex increased cell viability under hypoxia induced by $CoCl_2$ and suppressed the expression of CD81 and GFAP up-regulated by hypoxia. Conclusion : These results suggest that the Moutan Redicis Cortex could promote neural regeneration as a consequence of protecting CNS cells from hypoxia and suppressing the reactive gliosis following CNS injury.

중추신경계 손상 회복에 미치는 대한 조구등의 영향

이진구,박형진,김동웅,송봉근,Lee, Jin-Goo,Park, Hyoung-Jin,Kim, Dong-Woong,Song, Bong-Keun 대한약침학회 2009 Journal of pharmacopuncture Vol.12 No.1

Objective : Following central nervous system(CNS) injury, inhibitory influences at the site of axonal damage occur. Glial cells become reactive and form a glial scar, gliosis. Also myelin debris such as MAG inhibits axonal regeneration. Astrocyte-rich gliosis relates with up-regulation of GFAP and CD81, and eventually becomes physical and mechanical barrier to axonal regeneration. MAG is one of several endogenous axon regeneration inhibitors that limit recovery from CNS injury and disease. It was reported that molecules that block such inhibitors enhanced axon regeneration and functional recovery. Recently it was reported that treatment with anti-CD81 antibodies enhanced functional recovery in the rat with spinal cord injury. So in this current study, the author investigated the effect of the water extract of Uncariae Ramulus et Uncus on the regulation of CD81, GFAP and MAG that increase when gliosis occurs. Methods : MTT assay was performed to examine cell viability, and cell-based ELISA, western blot and PCR were used to detect the expression of CD81, GFAP and MAG. Then also immunohistochemistry was performed to confirm in vivo. Results : Water extract of Uncariae Ramulus et Uncus showed relatively high cell viability at the concentration of 0.05%, 0.1% and 0.5%. The expression of CD81, GFAP and MAG in astrocytes was decreased after the administration of Uncariae Ramulus et Uncus water extract. These results was confirmed in the brain sections following cortical stab injury by immunohistochemistry. Conclusion : The authors observed that Uncariae Ramulus et Uncus significantly down-regulates the expression of CD81, GFAP and MAG. These results suggest that Uncariae Ramulus et Uncus can be a candidate to regenerate CNS injury.

가토에서 트리암시놀론 유리체내 주사가 국소 망막박리에 미치는 영향

김무연,이영춘,박영훈 대한안과학회 2008 대한안과학회지 Vol.49 No.4

Purpose: To investigate the effect of localized retinal detachment on both the detached and attached regions, and to determine the effect of triamcinolone on Müller cell gliosis. Methods: Pars plana vitrectomy was performed in both eyes of 12 pigmented rabbits. A dome‐shaped retinal detachment was made by injecting sodium hyaluronate into the subretinal space. Triamcinolone (5 mg) was applied intravitreally to one eye (12 eyes). The detached retinal area and the neighboring attached region were studied by light and electron microscopy 3, 7, and 28 days after surgery. Tissues were prepared in 5 um sections for hematoxylin-eosin staining and immunohistochemistry with antibody to glial fibrillary acidic protein (GFAP). Results: In addition to the well-known degeneration of photoreceptor cells in the detached retina, an incomplete but severe loss of ganglion cell axons occurs in both the detached and the attached regions. The total retinal thickness gradually decreased in the detached areas, while the thickness of the inner retinal layers remained virtually unchanged over several weeks. Gliotic alterations were apparent in both the detached and non-detached retinal areas, and intravitreal triamcinolone did not alter these gliotic alterations of Müller cells. Conclusions: It is noteworthy that progressive retinal destruction also occurs in the attached retina after local detachment. This may account for visual impairment in strikingly large areas of the visual field, even after retinal reattachment.

신경세포가 별아교세포의 아교섬유성 산단백질 표현에 미치는 영향

배형미,박정선,연동수,Bae Hyung-Mi,Park Jung-Sun,Yeon Dong-Soo 대한약리학회 1997 The Korean Journal of Physiology & Pharmacology Vol.1 No.3

Injury to brain transforms resting astrocytes to their reactive form, the hallmark of which is an increase in glial fibrillary acidic protein (GFAP), the major intermediate filament protein of their cell type. The overall glial response after brain injury is referred to as reactive gliosis. Glial-neuronal interaction is important for neuronal migration, neurite outgrowth and axonal guidance during ontogenic development. Although much attention has been given to glial regulation of neuronal development and regeneration, evidences also suggest a neuronal influence on glial cell differentiation, maturation and function. The aim of the present study was to analyze the effects of glial-hippocampal neuronal co-culture on GFAP expression in the co-cultured astrocytes. The following antibodies were used for double immunostaining chemistry; mouse monoclonal antibodies for confirm neuronal cells, rabbit anti GFAP antibodies for confirm astrocytes. Primary cultured astrocytes showed the typical flat polygonal morphology in culture and expressed strong GFAP and vimentin. Co-cultured hippocampal neurons on astrocytes had phase bright cell body and well branched neurites. About half of co-cultured astrocytes expressed negative or weak GFAP and vimentin. After 2 hour glutamate (0.5 mM) exposure of glial-neuronal co-culture, neuronal cells lost their neurites and most of astrocytes expressed strong CFAE and vimentin. In Western blot analysis, total GFAP and vimentin contents in co-cultured astrocytes were lower than those of primary cultured astrocytes. After glutamate exposure of glial-neuronal co-culture, GFAP and vimentin contents in astrocytes were increased to the level of primary cultured astrocytes. These results suggest that neuronal cell decrease GFAP expression in co-cultured astrocytes and hippocampal neuronal-glial co-culture can be used as a reactive gliosis model in vitro for studying GFAP expression of astrocytes.

Alendronate Enhances Functional Recovery after Spinal Cord Injury

최유나,신태균 한국뇌신경과학회 2022 Experimental Neurobiology Vol.31 No.1

Spinal cord injury is a destructive disease characterized by motor/sensory dysfunction and severe inflammation. Alendronate is an anti-inflamma- tory molecule and may therefore be of benefit in the treatment of the inflammation associated with spinal cord injury. This study aimed to evaluate whether alendronate attenuates motor/sensory dysfunction and the inflammatory response in a thoracic spinal cord clip injury model. Alendro- nate was intraperitoneally administered at 1 mg/kg/day or 5 mg/kg/day from day (D) 0 to 28 post-injury (PI). The histopathological evaluation showed an alleviation of the inflammatory response, including the infiltration of inflammatory cells, and a decrease in gliosis. Alendronate also led to reductions in the levels of inflammation-related molecules, including mitogen-activated protein kinase, p53, pro-inflammatory cytokines, and pro-inflammatory mediators. Neuro-behavioral assessments, including the Basso, Beattie, and Bresnahan scale for locomotor function, the von Frey filament test, the hot plate test, and the cold stimulation test for sensory function, and the horizontal ladder test for sensorimotor function improved significantly in the alendronate-treated group at D28PI. Taken together, these results suggest that alendronate treatment can inhibit the inflammatory response in spinal cord injury thus improving functional responses.

Local exposure of 849 MHz and 1763 MHz radiofrequencyradiation to mouse heads does not induce cell death or cellproliferation in brain

김태형,Tai-Qin Huang,장자준,Man Ho Kim,Hyun-Jeong Kim,Jae-Seon Lee,Jeong Ki Pack,Jeong-Sun Seo,Woong-Yang Park 생화학분자생물학회 2008 Experimental and molecular medicine Vol.40 No.3

Even though there is no direct evidence to prove the cellular and molecular changes induced by radiofrequency (RF) radiation itself, we cannot completely exclude the possibility of any biological effect of mobile phone frequency radiation. We established a carousel- type exposure chamber for 849 MHz or 1763 MHz of mobile phone RF radiation to expose RF to the heads of C57BL mice. In this chamber, animals were irradiated intermittently at 7.8 W/kg for a maximum of 12 months. During this period, the body weights of 3 groups-sham, 849 MHz RF, and 1763 MHz RF-did not show any differences between groups. The brain tissues were obtained from 3 groups at 6 months and 12 months to examine the differences in histology and cell proliferation between control and RF exposure groups, but we could not find any change upon RF radiation. Likewise, we could not find changes in the expression and distribution of NeuN and GFAP in hippocampus and cerebellum, or in cell death by TUNEL assay in RF exposure groups. From these data, we conclude that the chronic exposure to 849 MHz and 1763 MHz RF radiation at a 7.8 W/kg specific absorption rate (SAR) could not induce cellular alterations such as proliferation, death, and reactive gliosis.

공진단이 MCAO모델 흰쥐에서 gliosis 억제에 미치는 영향

성기문,허래경,송봉근 대한한방내과학회 2009 大韓韓方內科學會誌 Vol.30 No.4

Objectives : In conditions of brain infarction, irreversible axon damage occurs in the central nerve system (CNS), because gliosis becomes physical and a mechanical barrier to axonal regeneration. Reactive gliosis induced by ischemic injury such as middle cerebral artery occlusion is involved with up-regulation of GFAP and CD81. The current study was to examine the effect of the Gongjin-dan (GJD) on CD81 and GFAP expression and its pathway in the rat brain following middle cerebral artery occlusion (MCAO). Methods : In order to study ischemic injuries on the brain, infarction was induced by MCAO using insertion of a single nylon thread, through the internal carotid artery, into a middle cerebral artery. Cresyl violet staining, cerebral infarction size measurement, immunohistochemistry and microscopic examination were used to detect the expression of CD81 and GFAP and the effect on the infarct size and pyramidal cell death in the brain of the rat with cerebral infarction induced by MCAO. Also, c-Fos and ERK expression was measured to investigate the signaling pathway after GJD administration in MCAO rats. Results : The following results were obtained: Measuring the size of cerebral infarction induced by MCAO in the rat after injection of GJD showed the size was decreased. GJD administration showed pyramidal cell death protection in the hippocampus in the MCAO rat. GJD administration decreased GFAP expression in the MCAO rat. GJD administration decreased CD81 expression in the MCAO rat. GJD administration induced up-regulation of c-FOS expression compared with MCAO. GJD administration induced down-regulation of ERK expression compared with MCAO. Conclusion : We observed that GJD could suppress the reactive gliosis, which disturbs the axonal regeneration in the brain of the rat with cerebral infarction after MCAO by controlling the expression of CD81 and GFAP. The effect may be modulated by the regulation of c-Fos and ERK. These results suggest that GJD can be a candidate to regenerate CNS injury. Objectives : In conditions of brain infarction, irreversible axon damage occurs in the central nerve system (CNS), because gliosis becomes physical and a mechanical barrier to axonal regeneration. Reactive gliosis induced by ischemic injury such as middle cerebral artery occlusion is involved with up-regulation of GFAP and CD81. The current study was to examine the effect of the Gongjin-dan (GJD) on CD81 and GFAP expression and its pathway in the rat brain following middle cerebral artery occlusion (MCAO). Methods : In order to study ischemic injuries on the brain, infarction was induced by MCAO using insertion of a single nylon thread, through the internal carotid artery, into a middle cerebral artery. Cresyl violet staining, cerebral infarction size measurement, immunohistochemistry and microscopic examination were used to detect the expression of CD81 and GFAP and the effect on the infarct size and pyramidal cell death in the brain of the rat with cerebral infarction induced by MCAO. Also, c-Fos and ERK expression was measured to investigate the signaling pathway after GJD administration in MCAO rats. Results : The following results were obtained: Measuring the size of cerebral infarction induced by MCAO in the rat after injection of GJD showed the size was decreased. GJD administration showed pyramidal cell death protection in the hippocampus in the MCAO rat. GJD administration decreased GFAP expression in the MCAO rat. GJD administration decreased CD81 expression in the MCAO rat. GJD administration induced up-regulation of c-FOS expression compared with MCAO. GJD administration induced down-regulation of ERK expression compared with MCAO. Conclusion : We observed that GJD could suppress the reactive gliosis, which disturbs the axonal regeneration in the brain of the rat with cerebral infarction after MCAO by controlling the expression of CD81 and GFAP. The effect may be modulated by the regulation of c-Fos and ERK. These results suggest that GJD can be a candidate to regenerate CNS injury.

당귀 추출물 정맥 주사가 Middle Cerebral Artery Occlusion 모델 흰쥐에서 Gliosis 억제에 미치는 영향

송봉근,전용철,김선애,심안나,성기문,이언정,Song, Bong-Keun,Jeon, Yong-Cheol,Kim, Sun-Ae,Shim, An-Na,Seong, Kee-Moon,Lee, Eon-Jeon 대한약침학회 2011 Journal of pharmacopuncture Vol.14 No.3

Objectives : Gliosis becomes physical and mechanical barrier to axonal regeneration. Reactive gliosis induced by middle cerebral artery occlusion is involved with up-regulation of CD81 and GFAP (Glial fibrillary acidic protein). The current study is to examine the effect of the Angelica gigas Nakai(intravenous injection. 100 mg/kg twice in a day) on CD81 and GFAP of the rat in the brain after middle cerebral artery occlusion. Methods : Cerebral infarction was induced by middle cerebral artery occlusion. And after intravenous injection of water extract of Angelica gigas Nakai, the size of cerebral infarction was measured. Examination of optical microscope were also used to detect the expression of CD81 and GFAP in the brain of the rat. Results : The following results were obtained : We found that size of cerebral infarcion induced by MCAO (Middle Cerebral Artery Occlusion) in rats were decreased after intravenous injection of Angelica gigas Nakai. We injected the extract of Angelica gigas Nakai to the MCAO in rats, and the optical microscope study showed that Angelica gigas Nakai had effect on protecting the cells of hippocampus. We found that GFAP, CD81 and ERK of the brain in rats with cerebral infarction after MCAO were meaningfully decreased after intravenous injecting Angelica gigas Nakai. We found that c-Fos expression of the brain in rats with cerebral infarction after MCAO were significantly increased after intravenous injecting Angelica gigas Nakai. Conclusions : These results indicate that Angelica gigas Nakai could suppress the reactive gliosis, which disturbs the astrocyte regeneration in the brain of the rat with cerebral infarction after MCAO by controlling the expression of CD81 and GFAP. And the effect may be modulated by the up-regulation of c-Fos and ERK.

공진단이 MCAO모델 흰쥐에서 gliosis 억제에 마치는 영향

성기문,허래경,송봉곤,Seong, Kee-Moon,Hae, Rae-Kyong,Song, Bong-Keun 대한한방내과학회 2009 大韓韓方內科學會誌 Vol.30 No.4

Objectives : In conditions of brain infarction, irreversible axon damage occurs in the central nerve system (CNS), because gliosis becomes a physical and a mechanical barrier to axonal regeneration. Reactive gliosis induced by ischemic injury such as middle cerebral artery occlusion is involved with up-regulation of GFAP and CD81. This study was undertaken to examine the effect of the Gongjin-dan (GJD) on CD81 and GFAP expression and its pathway in the rat brain following middle cerebral artery occlusion (MCAO). Methods : In order to study ischemic injuries on the brain, infarction was induced by MCAO using insertion of a single nylon thread, through the internal carotid artery, into a middle cerebral artery. Cresyl violet staining, cerebral infarction size measurement, immunohistochemistry and microscopic examination were used to detect the expression of CD81 and GFAP and the effect on the infarct size and pyramidal cell death in the brain of the rat with cerebral infarction induced by MCAO. Also, c-Fos and ERK expression were measured to investigate the signaling pathway after GJD administration in MCAO rats. Results : Measuring the size of cerebral infarction induced by MCAO in the rat after injection of GJD showed the size had decreased. GJD administration showed pyramidal cell death protection in the hippocampus in the MCAO rat. GJD administration decreased GF AP expression in the MCAO rat. GJD administration decreased CD81 expression in the MCAO rat. GJD administration induced up-regulation of c-FOS expression compared with MCAO. GJD administration induced down-regulation of ERK expression compared with MCAO. Conclusion : We observed that GJD could suppress the reactive gliosis, which disturbs the axonal regeneration in the brain of a rat with cerebral infarction after MCAO by controlling the expression of CD81 and GFAP. The effect may be modulated by the regulation of c-Fos and ERK. These results suggest that GJD can be a candidate to regenerate CNS injury.