• BMB Reports
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• 제57권4호
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• pp.182-187
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• 2024

Neural stem cells (NSCs) in the adult hippocampus divide infrequently; the endogenous molecules modulating adult hippocampal neurogenesis (AHN) remain largely unknown. Here, we show that ErbB3 binding protein 1 (Ebp1), which plays important roles in embryonic neurodevelopment, acts as an essential modulator of adult neurogenic factors. In vivo analysis of Ebp1 neuron depletion mice showed impaired AHN with a low number of hippocampal NSCs and neuroblasts. Ebp1 leads to transcriptional repression of Bmp4 and suppression of Ascl1 promoter methylation in the dentate gyrus of the adult hippocampus reflecting an unusually high level of Bmp4 and low Ascl1 level in neurons of Ebp1-deficient mice. Therefore, our findings suggests that Ebp1 could act as an endogenous modulator of the interplay between Bmp4 and Ascl1/Notch signaling, contributing to AHN.

• Korean Journal of Acupuncture
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• 제24권4호
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• pp.99-110
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• 2007

Objectives : Epilepsy is one of the most common serious brain disorders that affect people of all ages, and it is characterized by recurrent unprovoked seizures. We examined whether acupuncture can reduce both the incidence of seizures and hippocampal cell death in dentate gyrus (DG) using a mouse model of kainic acid (KA)-induced epilepsy. Methods : ICR mice ($20{\sim}25$ g) were given acupuncture once a day at acupoint HT8 (sobu) bilaterally during 2 days before KA injection. After an intracerebroventricular injection of 0.1${\mu}g$ of KA, acupuncture treatment was subsequently administered once more (total 3 times), and the degree of seizure was observed for 20 min. Three hours after injection, we confirmed the neural cell death using cresyl violet staining and silver impregnation staining, and determined the expressions of c-Fos and glutamate decarboxylase (GAD)-67 using immunohistochemistry techniques in the DG. Results : KA induced epileptic seizure, neural cell death, increased c-Fos expression and decreased GAD-67 expression in the DG. Acupuncture treatment at HT8 reduced the severity of the epileptic seizure and inhibited neural cell death from KA. In addition, acupuncture normalized the expressions of c-Fos and GAD-67 in the same areas. Conclusions : These results demonstrated that acupuncture treatment at HT8 may reduce the KA-induced epileptic seizure and neural cell death in the DG possibly by normalizing c-Fos expressions and the gamma-aminobutyric acid neurons.

• Journal of Acupuncture Research
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• 제23권5호
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• pp.187-198
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• 2006

Objectives : The purpose of this study is to assess the effect of Daekumeumja herb-acupuncture on neural cell proliferation and nitric oxide synthase(NOS) expression in hippocampus of ethanol-intoxicated Sprague-Dawley(SD) rats. Methods : SD rats were randomly assigned into 5 groups ; the normal group, the alcohol-treated(control) group, the alcohol- and 1 mg/kg Daekumeumja- treated(sample A) group, the alcohol- and 5mg/kg Daekumeumja-treated (sample B) group, the alcohol- and 10 mg/kg Daekumeumja-treated (sample C) group(n = 6 in each group). Normal group were received with Saline, while control group were injected intraperitoneally with alcohol(2 g/kg) once per day for 5 days. Sample groups were treated Daekumeumja herb-acupuncture on Chungwan(CV12) for 5 consecutive days. Bromo-deoxyuridine(BrdU) was injected into all animals once per day for 5 days. For the detection of BrdU-positive cells and NADPH-d- positive cells in hippocampus, immunohistochemistry was performed. Results : 1. In the dentate gyrus area, the number of BrdU-positive cells in the sample $B(278.08{\pm}6.46)$, $C(331.33{\pm}16.68)$ groups was significantly(p<0.05) increased compared with the control group. 2. In the dentate gyrus area, the number of NADPH-d-positive cells in the sample $C(86.50{\pm}10.02)$ groups was significantly(p<0.05) increased compared with the control group. 3. In the CAI area, the number of NADPH-d-positive cells in the sample $A(63.90{\pm}2.69)$, $B(75.70{\pm}3.01)$, $C(97.70{\pm}4.06)$ groups was significantly(p<0.05) increased compared with the control group. 4. In the CA 2-3 area, the number of NADPH-d-positive cells in the sample $B(30.20{\pm}1.89)$, $C(62.70{\pm}2.08)$ groups was significantly(p<0.05) increased compared with the control group. Conclusion : These results indicate that, neural cell proliferation and NOS expression in hippocampus was reduced in ethanol-intoxicated group. Treatment of Daekumeumja herb-acupuncture increased this diminution. Daekumeumja could be able to effect on the prevention of the amnesia and learning disability in alcoholism.

• 동의생리병리학회지
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• 제31권1호
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• pp.65-74
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• 2017

Sleep deprivation is an extremely common event in today's society. It has caused learning cognitive skill deterioration and poor concentration, increased disease such as heart disease, diabetes and obesity, sexual function decrease, infertility increase, depression and autonomic nervous system disorder. Sleep deprivation-induced stress caused NADPH oxidase and oxidative stress. And this oxidative stress induces apoptosis. Lilii bulbus and Nelumbins semen are known to mental and physical relaxation effects. In this study, we induced sleep deprivation(SD) in Sprague-Dawley rats in water for 5 days and thereafter administered orally L. bulbus and N. semen for 5 days. Brain tissues were observed by histochemical, immunohistochemical and tunel staining. The immunoreactives of Tumor necrosis factor ${\alpha}$, Neuronal nitric oxide synthases, Phospho-SAPK/JNK and gp91-phox of the L. bulbus administered group and N. semen administered group were weaker than those of sleep deprivation group. In the L. bulbus administered group and N. semen administered group, apoptosis was decreased than that of sleep deprivation group. Proapoptotic p53, Bax, Cleaved caspase 3 immunoreactives of the administered group were weaker than those of sleep deprivation group, whereas anti-apoptotic Bcl-2 immunoreactity was stronger in the L. bulbus administered group and N. semen administered group. Antioxidant mechanism such as DJ-1, superoxide dismutase 1, Nuclear factor-like 2 immunoreactives of the L. bulbus and N. semen administered group were stronger than those of sleep deprivation group. These results demonstrate that L. bulbus, N. semen had the neuroprotective effects on the sleep deprivation-induced oxidative stress in the hippocampus.

• The Korean Journal of Physiology and Pharmacology
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• 제20권1호
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• pp.41-51
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• 2016

Adult hippocampal dentate granule neurons are generated from neural stem cells (NSCs) in the mammalian brain, and the fate specification of adult NSCs is precisely controlled by the local niches and environment, such as the subventricular zone (SVZ), dentate gyrus (DG), and Toll-like receptors (TLRs). Epigallocatechin-3-gallate (EGCG) is the main polyphenolic flavonoid in green tea that has neuroprotective activities, but there is no clear understanding of the role of EGCG in adult neurogenesis in the DG after neuroinflammation. Here, we investigate the effect and the mechanism of EGCG on adult neurogenesis impaired by lipopolysaccharides (LPS). LPS-induced neuroinflammation inhibited adult neurogenesis by suppressing the proliferation and differentiation of neural stem cells in the DG, which was indicated by the decreased number of Bromodeoxyuridine (BrdU)-, Doublecortin (DCX)- and Neuronal Nuclei (NeuN)-positive cells. In addition, microglia were recruited with activating TLR4-NF-${\kappa}B$ signaling in the adult hippocampus by LPS injection. Treating LPS-injured mice with EGCG restored the proliferation and differentiation of NSCs in the DG, which were decreased by LPS, and EGCG treatment also ameliorated the apoptosis of NSCs. Moreover, pro-inflammatory cytokine production induced by LPS was attenuated by EGCG treatment through modulating the TLR4-NF-${\kappa}B$ pathway. These results illustrate that EGCG has a beneficial effect on impaired adult neurogenesis caused by LPS-induced neuroinflammation, and it may be applicable as a therapeutic agent against neurodegenerative disorders caused by inflammation.

• 대한한의학회지
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• 제23권3호
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• pp.26-32
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• 2002

목적 : 본 연구에서는 알코올 독성에 대하여 흰쥐의 치상회에서 새로운 신경세포의 생성 및 nitric oxide synthase (NOS) 발현에 인삼이 미치는 영향을 5-bromo-2-deoxyuridine (BrdU) 면역 조직 화학법 및 nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) 조직화학법을 통해서 관찰하고자 한다. 방법 : 실험동물을 정상군, 인삼처치군, 알코올처치군 및 알코올-인삼 처치군으로 분류하여 각각의 실험군에 3일간 BrdU (50mg/kg)를 복강주사하였다. 인삼처치군은 30mg/kg 용량의 인삼 전탕액을 중완혈에 약침주사하였고, 알코올 처치군은 2 g/kg 용량의 알코올을 투여하였으며. 알코올-인삼 처치군은 2 g/kg 용량의 알코올 및 30mg/kg 용량의 인삼 전탕액을 투여한 후 각각의 BrdU 양성 세포수와 NADPH-d 양성세포수를 관찰하였다. 결과 : 알코올 투여군은 BrdU 양성세포 및 NADPH-d 양성세포 발현이 감소하였으나, 인삼 및 알코올 인삼처치군에서는 알코올 투여군에 비해서 모두 증가하였다. 결론 : 인삼은 알코올에 의해서 유발된 새로운 신경세포 생성의 감소에 대하여 보호효과가 있으며, 알코올에 의해서 부가적으로 영향 받는 산화질소는 세포생성 조절에 중요한 역할을 하는 것으로 사려된다.

• Animal cells and systems
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• 제15권4호
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• pp.268-273
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• 2011

Transgenic mice expressing green fluorescent protein (GFP) under the control of human glial fibrillary acidic protein promoter (hGFAP) have been utilized for in vivo labeling of astrocytes. Although it has been considered that virtually all astrocytes express GFP in this transgenic mouse, we found that different subsets of GFAP-expressing astrocytes express considerably different levels of GFP in the adult brain. Astrocytes in the spinal cord, the molecular layer of thecerebellum, meninges, white matter, corpus callosum and blood vessels exhibited strong GFP, whereas subsets of astrocytes associated with granule cells in the cerebellum and dentate gyrus did not or only marginally exhibited GFP. We also found that a small subset of GFP-expressing cells in the periglomeruli of the olfactory bulb did not express GFAP immunoreactivity. Collectively, these results suggest that human GFAP promoter-derived GFP expression does not faithfully recapitulate the endogenous GFAP expression in mice, suggesting that upstream regulatory mechanisms controlling GFAP transcription are different in different populations of astrocytes, and may reflect the functional diversity of astrocytes.

• 한국발생생물학회지:발생과생식
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• 제17권3호
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• pp.179-186
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• 2013

Neural stem cells are found in adult mammalian brain regions including the subgranular zone (SGZ) of the dentate gyrus (DG) and the subventricular zone (SVZ). In addition to these two regions, other neurogenic regions are often reported in many species. Recently, the subcallosal zone (SCZ) has been identified as a novel neurogenic region where new neuroblasts are spontaneously generated and then, by Bax-dependent apoptosis, eliminated. However, the development of SCZ in the postnatal brain is not yet fully explored. The present study investigated the precise location and amount of neuroblasts in the developing brain. To estimate the importance of programmed cell death (PCD) for SCZ histogenesis, SCZ development in the Bax-knockout (KO) mouse was examined. Interestingly, an accumulation of extra neurons with synaptic fibers in the SCZ of Bax-KO mice was observed. Indeed, Bax-KO mice exhibited enhanced startle response to loud acoustic stimuli and reduced anxiety level. Considering the prevention of PCD in the SCZ leads to sensory-motor gating dysfunction in the Bax-KO mice, active elimination of SCZ neuroblasts may promote optimal brain function.

• Journal of Korean Neurosurgical Society
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• 제29권7호
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• pp.861-867
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• 2000

Purpose : Neuronal migration disorder(NMD) is a major underlying pathology of patients with intractable epilepsy. The role of NMD on seizure susceptibility or epileptogenecity, however, has not been documented. Methods : External irradiation of total amount of 250 cGY was performed to the fetal rats on days 16(E16) and 17(E17) of gestation. After delivery, the rats of 230-260g were decapitated for the histopathologic study. Epileptog-enecity of the NMD was studied by observing electroclinical events after intraperitoneal kainic acid(KA) injection in the control rats and NMD rats. Results : Histopathologic findings revealed focal and/or diffuse cortical dysplasia consisting of dyslamination of the cerebral cortex and appearance of the cytomegalic neurons, neuronal heterotopia in the periventricular white matter, dispersion of the pyramidal layer and the dentate gyrus of the hippocampus, and agenesis of the corpus callosum. Abnormal expression of neurofilaments protein(NF-M/H) was characteristically observed in the dysplastic neurons of the neocortex and hippocampus. Early ictal onset and prolonged ictal activity on EEG and clinical seizures were observed from the NMD rats unlike with the control rats. Conclusions : Exteranl irradiation on the fetal rats produced NMD. And the rats with NMD were highly susceptible to kainic acid provoked seizures. This animal model would be useful to study the pathophysiology of clinically relevant NMDs.

• Clinical and Experimental Pediatrics
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• 제56권10호
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• pp.446-450
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• 2013

Purpose: This study evaluated the extent of damage due to hypothermia in the mature and immature brain. Methods: Hippocampal tissue cultures at 7 and 14 days in vitro (DIV) were used to represent the immature and mature brain, respectively. The cultures were exposed at $25^{\circ}C$ for 0, 10, 30, and 60 minutes (n=30 in each subgroup). Propidium iodide fluorescent images were captured 24 and 48 hours after hypothermic injury. Damaged areas of the cornu ammonis 1 (CA1), CA3, and dentate gyrus (DG) were measured using image analysis. Results: At 7 DIV, the tissues exposed to cold injury for 60 minutes showed increased damage in CA1 (P<0.001) and CA3 (P=0.005) compared to the control group at 48 hours. Increased damage to DG was observed at 24 (P=0.008) and 48 hours (P=0.011). The 14 DIV tissues did not demonstrate any significant differences compared with the control group, except for the tissues exposed for 30 minutes in which DG showed less damage at 48 hours than the control group (P=0.048). In tissues at 7 DIV, CA1 (P=0.040) and DG (P=0.013) showed differences in the duration of cold exposure. Conclusion: The immature brain is more vulnerable to hypothermic injury than the mature brain.