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The discovery of neuroglobin (Ngb), a brain- or neuron-specific member of the hemoglobin family, has revolutionized our understanding of brain oxygen metabolism. Currently, how Ngb plays such a role remains far from clear. Here, we report a novel mechanism by which Ngb might facilitate neuronal oxygenation upon hypoxia or anemia. We found that Ngb was present in, co-localized to, and co-migrated with mitochondria in the cell body and neurites of neurons. Hypoxia induced a sudden and prominent migration of Ngb towards the cytoplasmic membrane (CM) or cell surface in living neurons, and this was accompanied by the mitochondria. In vivo, hypotonic and anemic hypoxia induced a reversible Ngb migration toward the CM in cerebral cortical neurons in rat brains but did not alter the expression level of Ngb or its cytoplasm/mitochondria ratio. Knock-down of Ngb by RNA interference significantly diminished respiratory succinate dehydrogenase (SDH) and ATPase activity in neuronal N2a cells. Over-expression of Ngb enhanced SDH activity in N2a cells upon hypoxia. Mutation of Ngb at its oxygen-binding site (His64) significantly increased SDH activity and reduced ATPase activity in N2a cells. Taken together, Ngb was physically and functionally linked to mitochondria. In response to an insufficient oxygen supply, Ngb migrated towards the source of oxygen to facilitate neuronal oxygenation. This novel mechanism of neuronal respiration provides new insights into the understanding and treatment of neurological diseases such as stroke and Alzheimer's disease and diseases that cause hypoxia in the brain such as anemia.
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Ratos , Animais , Neuroglobina/metabolismo , Globinas/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Hipóxia/metabolismo , Encéfalo/metabolismo , Oxigênio , Anemia/metabolismo , Adenosina Trifosfatases/metabolismoRESUMO
Objective Saiga antelope is a small population inhabiting in desert and semi desert areas of national and world endangered protected animals, its wild population is extremely rare. In order to explore the correlation between hypoxic tolerance and neuroglobin (NGB) in Saiga antelope. A female Saiga antelope died of dystocia was used as the experimental animal, and the tissue samples were sampled repeatedly for 3 times to study the distribution and expression of NGB in brain of Saiga antelope in the process of adapting to hypoxia. Methods The distribution and expression of NGB in the parietal lobe, frontal lobe, temporal lobe, occipital lobe, hypothalamus, hippocampus, pear like leaf, cingulate gyrus, striatum and thalamus of Saiga antelope were detected by immunohistochemistry(IHC) and Real-time PCR. Results The result of IHC showed that NGB was positive in all parts of Saiga antelope brain, and the cells that had positive reactions in the parietal, frontal, temporal and occipital lobes of the cerebral cortex were mostly granular cells and martinotti cells. NGB was found in the granular cell layer, pyramidal cell layer and molecular cell layer in hippocampus, and the positive staining of pyramidal cell layer was the strongest. NGB positive expression in Pear like leaves and hypothalamus mainly occured in multi-type cells. NGB was expressed in the granulocytes and glial cells of cingulate gyrus, mainly in the granular cells. The positive expression of NGB in striatum was mainly located in granular cells, the positive expression of NGB in thalamus could be seen in the polymorphosis and glial cells, and the positive substance of the multi-type cells was obviously colored. The result of Real-time PCR showed that NGB was expressed in different regions of Saiga antelope brain, the highest expression in the frontal lobe of the cerebral cortex, the second in the parietal lobe, and the expression was significantly higher than that in the rest of the brain tissue (P0.05). Conclusion The expression of NGB in different regions of Saiga antelope has some selective differences in the long-term adaptation to hypoxia environment. The frontal and parietal lobes have the highest tolerance to hypoxia, followed by hippocampus, and the striatum is the weakest, which may be related to the specific functions of different regions of brain tissue, but the specific mechanism remains to be further explored.
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Abstract Background The brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. Aim The study examined the expression of Neuroglobin (Ngb) and Hypoxia-inducible factor-1α (Hif-1α) in adult and young yak brain tissues, and provided researchers with meaningful insight into the anatomy, physiology, and biochemistry of this mammal. Method The study employed immunohistochemistry (IHC), quantitative real-time PCR (qRT-PCR), and Western blot (WB) to obtain the results. Results Ngb and Hif-1α were significantly (P<0.05) expressed in the cerebellar cortex, piriform lobe, medulla, and corpus callosum of the adult yak while in the young yak brain tissues, the protein expressions were significantly found in the white matter of the cerebellum, pineal gland, corpus callosum, and cerebellar cortex. The Ngb and Hif-1α expression showed similarities and differences. This may have resulted from similar animal species, source of nutrition, age factors, brain size, emotional activities, and communication. The findings documented that Ngb and Hif-1α are commonly expressed in various adult and young yak brain tissues. Multiple roles in the brain tissues of the adult and young yaks are involved in the expression and distribution and are proposed to play a significant role in the adaptation of the yak to the high altitude environment. Conclusion This study provides meaningful data to understand the adaptive mechanism to hypoxia and recommended researchers to expand on the adaptive mechanism and brain tissues that are not recorded.
Resumo Contexto O cérebro é um órgão que funciona como o centro do sistema nervoso em todos os animais vertebrados e na maioria dos invertebrados. Objetivo O estudo examinou a expressão de neuroglobina (Ngb) e fator-1α indutível por hipóxia (Hif-1α) em tecidos cerebrais de iaques adultos e jovens e forneceu aos pesquisadores uma visão significativa da anatomia, fisiologia e bioquímica desse mamífero. Método O estudo utilizou imuno-histoquímica (IHC), PCR quantitativo em tempo real (qRT-PCR) e western blot (WB) para a obtenção dos resultados. Resultados Ngb e Hif-1α foram significativamente (P < 0,05) expressos no córtex cerebelar, lobo piriforme, medula e corpo caloso do iaque adulto, enquanto nos tecidos cerebrais do iaque jovem as expressões proteicas foram encontradas significativamente na substância branca do cerebelo, glândula pineal, corpo caloso e córtex cerebelar. A expressão de Ngb e Hif-1α apresentou semelhanças e diferenças. Isso pode ter resultado de espécies animais semelhantes, fonte de nutrição, fatores de idade, tamanho do cérebro, atividades emocionais e comunicação. Os resultados documentaram que o Ngb e o Hif-1α são comumente expressos em vários tecidos cerebrais de iaques adultos e jovens. Múltiplos papéis nos tecidos cerebrais de iaques adultos e jovens estão envolvidos na expressão e distribuição e são propostos para desempenhar um papel significativo na adaptação do iaque ao ambiente de alta altitude. Conclusão Este estudo fornece dados significativos para compreender o mecanismo adaptativo à hipóxia e recomendou que os pesquisadores expandissem o mecanismo adaptativo e os tecidos cerebrais que não foram registrados.
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Animais , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Hipóxia , Encéfalo , RNA Mensageiro , Bovinos , NeuroglobinaRESUMO
Background: The brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. Aim: The study examined the expression of Neuroglobin (Ngb) and Hypoxia-inducible factor-1α (Hif-1α) in adult and young yak brain tissues, and provided researchers with meaningful insight into the anatomy, physiology, and biochemistry of this mammal. Method: The study employed immunohistochemistry (IHC), quantitative real-time PCR (qRT-PCR), and Western blot (WB) to obtain the results. Results: Ngb and Hif-1α were significantly (P<0.05) expressed in the cerebellar cortex, piriform lobe, medulla, and corpus callosum of the adult yak while in the young yak brain tissues, the protein expressions were significantly found in the white matter of the cerebellum, pineal gland, corpus callosum, and cerebellar cortex. The Ngb and Hif-1α expression showed similarities and differences. This may have resulted from similar animal species, source of nutrition, age factors, brain size, emotional activities, and communication. The findings documented that Ngb and Hif-1α are commonly expressed in various adult and young yak brain tissues. Multiple roles in the brain tissues of the adult and young yaks are involved in the expression and distribution and are proposed to play a significant role in the adaptation of the yak to the high altitude environment. Conclusion: This study provides meaningful data to understand the adaptive mechanism to hypoxia and recommended researchers to expand on the adaptive mechanism and brain tissues that are not recorded.
Contexto: O cérebro é um órgão que funciona como o centro do sistema nervoso em todos os animais vertebrados e na maioria dos invertebrados. Objetivo: O estudo examinou a expressão de neuroglobina (Ngb) e fator-1α indutível por hipóxia (Hif-1α) em tecidos cerebrais de iaques adultos e jovens e forneceu aos pesquisadores uma visão significativa da anatomia, fisiologia e bioquímica desse mamífero. Método: O estudo utilizou imuno-histoquímica (IHC), PCR quantitativo em tempo real (qRT-PCR) e western blot (WB) para a obtenção dos resultados. Resultados: Ngb e Hif-1α foram significativamente (P < 0,05) expressos no córtex cerebelar, lobo piriforme, medula e corpo caloso do iaque adulto, enquanto nos tecidos cerebrais do iaque jovem as expressões proteicas foram encontradas significativamente na substância branca do cerebelo, glândula pineal, corpo caloso e córtex cerebelar. A expressão de Ngb e Hif-1α apresentou semelhanças e diferenças. Isso pode ter resultado de espécies animais semelhantes, fonte de nutrição, fatores de idade, tamanho do cérebro, atividades emocionais e comunicação. Os resultados documentaram que o Ngb e o Hif-1α são comumente expressos em vários tecidos cerebrais de iaques adultos e jovens. Múltiplos papéis nos tecidos cerebrais de iaques adultos e jovens estão envolvidos na expressão e distribuição e são propostos para desempenhar um papel significativo na adaptação do iaque ao ambiente de alta altitude. Conclusão: Este estudo fornece dados significativos para compreender o mecanismo adaptativo à hipóxia e recomendou que os pesquisadores expandissem o mecanismo adaptativo e os tecidos cerebrais que não foram registrados.
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Animais , Adulto Jovem , Adulto , Bovinos , Bovinos , Cérebro/anatomia & histologia , Cérebro/fisiologia , Fator 1 Induzível por Hipóxia/análise , Fenômenos Bioquímicos , Neuroglobina/análiseRESUMO
Abstract Background The brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. Aim The study examined the expression of Neuroglobin (Ngb) and Hypoxia-inducible factor-1 (Hif-1) in adult and young yak brain tissues, and provided researchers with meaningful insight into the anatomy, physiology, and biochemistry of this mammal. Method The study employed immunohistochemistry (IHC), quantitative real-time PCR (qRT-PCR), and Western blot (WB) to obtain the results. Results Ngb and Hif-1 were significantly (P 0.05) expressed in the cerebellar cortex, piriform lobe, medulla, and corpus callosum of the adult yak while in the young yak brain tissues, the protein expressions were significantly found in the white matter of the cerebellum, pineal gland, corpus callosum, and cerebellar cortex. The Ngb and Hif-1 expression showed similarities and differences. This may have resulted from similar animal species, source of nutrition, age factors, brain size, emotional activities, and communication. The findings documented that Ngb and Hif-1 are commonly expressed in various adult and young yak brain tissues. Multiple roles in the brain tissues of the adult and young yaks are involved in the expression and distribution and are proposed to play a significant role in the adaptation of the yak to the high altitude environment. Conclusion This study provides meaningful data to understand the adaptive mechanism to hypoxia and recommended researchers to expand on the adaptive mechanism and brain tissues that are not recorded.
Resumo Contexto O cérebro é um órgão que funciona como o centro do sistema nervoso em todos os animais vertebrados e na maioria dos invertebrados. Objetivo O estudo examinou a expressão de neuroglobina (Ngb) e fator-1 indutível por hipóxia (Hif-1) em tecidos cerebrais de iaques adultos e jovens e forneceu aos pesquisadores uma visão significativa da anatomia, fisiologia e bioquímica desse mamífero. Método O estudo utilizou imuno-histoquímica (IHC), PCR quantitativo em tempo real (qRT-PCR) e western blot (WB) para a obtenção dos resultados. Resultados Ngb e Hif-1 foram significativamente (P 0,05) expressos no córtex cerebelar, lobo piriforme, medula e corpo caloso do iaque adulto, enquanto nos tecidos cerebrais do iaque jovem as expressões proteicas foram encontradas significativamente na substância branca do cerebelo, glândula pineal, corpo caloso e córtex cerebelar. A expressão de Ngb e Hif-1 apresentou semelhanças e diferenças. Isso pode ter resultado de espécies animais semelhantes, fonte de nutrição, fatores de idade, tamanho do cérebro, atividades emocionais e comunicação. Os resultados documentaram que o Ngb e o Hif-1 são comumente expressos em vários tecidos cerebrais de iaques adultos e jovens. Múltiplos papéis nos tecidos cerebrais de iaques adultos e jovens estão envolvidos na expressão e distribuição e são propostos para desempenhar um papel significativo na adaptação do iaque ao ambiente de alta altitude. Conclusão Este estudo fornece dados significativos para compreender o mecanismo adaptativo à hipóxia e recomendou que os pesquisadores expandissem o mecanismo adaptativo e os tecidos cerebrais que não foram registrados.
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Objective:To discuss the effect of acupuncture on learning and memory ability and the expression of neuroglobin (Ngb) of the hippocampus of vascular cognitive impaired (VCI) rats.Methods:VCI rats model was established by repeated ligation of the carotid arteries of the two sides to induce ischemia-reperfusion injury. The successful modeled rats were divided into acupuncture group and a model group according to the random number table method, with 12 rats in each group, and 12 rats were selected as the normal group. The rats in the acupuncture group received acupuncture at "Baihui", "Fengfu" and "Yongquan", 10 times as a course of treatment, a total of 3 courses, and stop acupuncture treatment for 2 days during the courses of treatment. Neurobehavioral scores were measured on the 3rd day after the intervention. Morris water maze was conducted to detect the learning and memory ability of the rats in each group, and Western blot was used to detect the expression of Ngb in the hippocampus of the rats.Results:Compared with the model group, the behavioral score of the acupuncture group decreased after intervention ( P<0.05), the escape latency was significantly shortened ( P<0.05), the number of crossing platforms was increased ( P<0.05), and the hippocampal Ngb (1.18±0.06 vs.0.98±0.04) was significantly increased ( P<0.05). Conclusion:Acupuncture at "Baihui", "Fengfu" and "Yongquan" could promote the expression of Ngb in the hippocampus of rats and improve the learning and memory ability of VCI rats.
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Objective:To investigate the relationship between serum ubiquitin C-terminal hydrolase-L1 (UCH-L1) and neuroglobin levels and the prognosis of neurological function in coma patients after cardiopulmonary resuscitation, and to analyze their value in predicting the prognosis of patients.Methods:From February 2018 to June 2020, 45 comatose patients admitted to the Chengdu Third People′s Hospital of Sichuan Province after successful cardiopulmonary resuscitation were prospectively selected as the coma group, and 62 patients admitted to the emergency intensive care unit during the same period after successful cardiopulmonary resuscitation with consciousness recovered within 24 hours were selected as the control group.Serum UCH-L1 and neuroglobin levels were detected within 24 hours after admission.Glasgow coma Scale (GCS)and cerebral performance category(CPC)were used to evaluate coma severity and neurological prognosis.Spearman rank correlation analyzed the correlation between UCH-L1 and neuroglobin levels and GCS and CPC scores.Logistic regression analyzed the factors affecting the prognosis of neurological function in coma patients after cardiopulmonary resuscitation.Receiver operating characteristic curve (ROC) was used to analyze the value of UCH-L1 and neuroglobin in predicting the prognosis of neurological function in coma patients after successful cardiopulmonary resuscitation.Results:In coma group, serum UCH-L1((0.63±0.21) μg/L) and the concentration of neuroglobin ((89.34±21.35) mg/L) was higher than that in the control group ((0.27±0.08) μg/L, (32.13±9.21) mg/L), the difference was statistically significant( t=12.338, 18.846; all P<0.001). The levels of UCH-L1 and neuroglobin in mild, medium and severe coma groups were increased in turn, and the differences between the groups were statistically significant( F=86.430, 26.958; all P<0.001). The serum levels of UCH-L1((0.72±0.06) μg/L)and neuroglobin ((100.35±5.79) mg/L)in the group with poor neurological prognosis were higher than those in the group with good neurological prognosis((0.52±0.08) μg/L, (75.58±6.91) mg/L), and the differences between the groups were statistically significant( t=9.585, 13.086; all P<0.001). UCH-L1 and neuroglobin were negatively correlated with GCS score(rs=-0.685, -0.669; all P<0.001), and positively correlated with CPC score (rs=0.688, 0.670; all P<0.001). Multivariate Logistic regression analysis showed that low GCS score( OR=0.552, 95% CI: 0.392-0.776, P<0.001), high UCH-L1 ( OR=1.881, 95% CI: 1.276-2.773, P<0.001)and neuroglobin( OR=1.677, 95% CI: 1.206-2.331, P=0.001)were independently associated with poor neurological outcomes in coma patients after cardiopulmonary resuscitation .The AUC of combining UCH-L1 and neuroglobin in predicting poor neurological outcomes in coma patients after cardiopulmonary resuscitation was 0.954, which was higher than that of UCH-L1 and neuroglobin alone (0.821, 0.790) ( Z=2.351, 2.649; all P<0.05). Conclusion:After successful cardiopulmonary resuscitation, the levels of UCH-L1 and neuroglobin in coma patients are increased.High levels of UCH-L1 and neuroglobin are associated with coma severity and neurological dysfunction, which can be used as a potential biological indicator for prognosis evaluation of neurological function.
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Objective:To evaluate the mechanism of dexmedetomidine alleviating sevoflurane-induced neurotoxicity and the relationship with neuroglobin (Ngb) in neonatal rats.Methods:Eighty-four healthy male Sprague-Dawley rats, aged 7 days, weighing 12-16 g, were divided into 4 groups ( n=21 each) using a random number table method: control group (group C), sevoflurane group (group S), sevoflurane plus dexmedetomidine group (group SD), and sevoflurane plus dexmedetomidine and yohimbine group (group SDY). Sevoflurane anesthesia method: anesthesia was induced by inhaling 8% sevoflurane and then maintained by inhaling 3% sevoflurane for 4 h. At the end of anesthesia, dexmedetomidine 50 μg/kg was intraperitoneally injected in group SD, and 0.5 mg/kg yohimbine (α 2 adrenergic receptor antagonist) was intraperitoneally injected immediately after the end of intraperitoneal injection of dexmedetomidine 50 μg/kg in group SDY.Six rats were randomly selected from each group and sacrificed at 24 h after the end of anesthesia.The brain tissues were removed for determination of histopathologic changes in hippocampal CA1 region (using HE staining), the expression of Ngb in the area of the hippocampus (by immunofluorescence staining) and the expression of cytochrome C (Cyt c) and caspase-3 (by Western blot). The other rats were fed until 28 days old, and Morris water maze test was performed. Results:Compared with group C, the expression of Ngb, Cyt c and caspase-3 was significantly up-regulated ( P<0.05), histopathologic changes in hippocampal CA1 region were accentuated, and Ngb fluorescence intensity was increased in group S. Compared with group S, the expression of Ngb was significantly up-regulated, expression of Cyt c and caspase-3 was down-regulated, the escape latency was shortened ( P<0.05), histopathologic changes in hippocampal CA1 region were reduced, and Ngb fluorescence intensity was increased in group SD.Compared with group SD, the expression of Ngb was significantly down-regulated, expression of Cyt c and caspase-3 was up-regulated, the escape latency was prolonged ( P<0.05), histopathologic changes in hippocampal CA1 region were accentuated, and Ngb fluorescence intensity was decreased in group SDY. Conclusion:The mechanism by which dexmedetomidine reduces sevoflurane-induced neurotoxicity may be related to activating α 2 adrenergic receptors and up-regulating the expression of Ngb in neonatal rats.
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Objective:To study the effect of rehabilitation training on the expression of neuroglobin (Ngb), oxidative stress and axon regeneration in the cortex and explore possible mechanisms of functional recovery after cerebral infarction.Methods:Thirty-six male Sprague-Dawley rats were randomly divided into a sham operation group, a model group and a rehabilitation group. Cerebral infarction was modelled in the model and rehabilitation groups using Longa′s middle cerebral artery occlusion (MCAO) technique. The sham operation group received the same procedure except that no thread was inserted to block the middle cerebral artery. The rats in the rehabilitation group began treadmill training 24h after the operation, while the other two groups were left on the treadmill without training. On the 3rd, 7th and 14th days after the operation, all of the rats′ neurological functioning was assessed using modified neurological severity scores (mNSSs). After the last mNSS test, all of the rats were sacrificed and peri-infarct brain tissue was resected to detect the expression of Ngb and oxidative stress indicators including superoxide dismutase (SOD), nitric oxide and malondialdehyde (MDA), as well as neurofilament-200 (NF-200) indicating axon regeneration.Results:On the 3rd day after the surgery there was no significant difference between the average mNSS scores of the rehabilitation and model groups. On the 7th and 14th day the average mNSS score of the rehabilitation group was significantly better than that of the model group. The average expression of Ngb in the model group was significantly higher than in the sham operation group. After the intervention, the average expression of SOD in the rehabilitation group was significantly higher than in the model group, while NO and MDA expression were significantly lower. After the intervention the average expression of NF-200 in the rehabilitation group was also significantly higher than in the model group.Conclusions:Rehabilitation training benefits the recovery of neurological function after cerebral infarction, at least in rats. The mechanism may be related to the upregulation of Ngb, alleviation of oxidative stress and enhancement of axonal regeneration in the peri-infarct cortex.
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Objective In this study, electroacupuncture (EA) was used to analyze the expression changes of related proteins in neuroglobin (NGB), PI3K/AKT and apoptotic pathways in the temporal cortex of bilirubin encephalopathy (BE) rats, so as to investigate the therapeutic effect of EA on BE and the relevant mechanism of NGB in this process. Totally 39 seven-day-old SD rats were divided into Sham, BE model and BE+EA groups. The neonatal BE model was established by injecting bilirubin solution (10 μg UCB/g Weight) into the cerebellomedullary cistern, Sham group was injected with the same amount of normal saline. BE rats were treated with EA at Baihui (GV20) and Quchi (LI11) acupoints with the frequency of 2/15 Hz for 15 min. Treatment was performed 12 h before modeling, followed by treatment every 12 h, in a total of three times. HE, Nissl staining and electron microscopy (TEM) were used to observe the pathological and ultrastructural changes of nerve cells in each group. Results showed that EA treatment reduced the damage of cortical neurons of BE rats and increase the number of Nissl bodies. TEM confirmed that EA treatment could alleviate the degree of mitochondria edema. Immunofluorescence staining was used to detect the expression sites and cell types of NGB. Results showed that NGB was mainly expressed in cortical neurons. Western blotting showed that EA treatment increased the expression of NGB, PI3K (p110 alpha), pAKT (Ser473) (P< 0. 05, P< 0. 05 and P< 0. 01, respectively) and the ratio of apoptosis-related protein Bcl-2/Bax (P < 0. 001), decreased the expression of Cleaved Caspase-3 (P< 0. 05) in the temporal cortex of rats. TUNEL staining showed that EA reduced the number of apoptotic cells (BE group 186. 00±13. 86 vs BE+EA group 78. 67±11. 85, P< 0. 01) . This study confirms that EA can promote the expression of NGB in the temporal cortex of BE rats, then activate the PI3K/AKT pathway to exert its neuroprotective function and inhibit the occurrence of apoptosis. EA may become a potential treatment method for BE.
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Neuroglobin (Ngb), a novel oxygen-carrying globin, has been shown to have neuroprotective effect on a variety of central nervous system disorders, and this protection is associated with maintenance of mitochondrial function. Therefore, this paper will focus on the recent biological functions of Ngb and Ngb-induced mitochondrial protection mechanisms.
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Objective To observe the influence of Hemin on both the expression of neuroglobin (Ngb) and Tau protein phosphorylation in rats with vascular dementia (VD),and explore the effect and mechanism of Ngb in VD. Methods VD model was established in rats with a permanent bilateral common carotid arteries occlusion(2-VO). Fifty four healthy male SD rats were randomly divided into 3 groups:sham operation group,VD group and Hemin group. According to ischemic time,the animals in each group were randomly allocated into 1 week subgroup,4 weeks subgroup and 8 weeks subgroup(n=6 in each subgroup). The learning and memory ability of rats were evaluated by Morris water maze test. The brain histopathological changes were observed by HE staining and the expression of Ngb and phosphorylated Tau ( p-Tau) was de-termined by Western blot. Results Compared with the sham operation group,after 2-VO the escape latency extended (all P<0. 05) and cross-platform performance reduced in rats in both VD group and Hemin group (all P<0. 05). The learning and memory ability of rats in Hemin group was better than that in VD group at the corresponding time point:the increase in the number of crossing platforms(1 week:Hemin group (7. 00± 0. 89) times vs VD group (5. 50±1. 22) times,t=2. 42,P<0. 05;4 weeks:Hemin group (5. 33±0. 52) times vs VD group (3. 50±1. 04) times,t=3. 84,P<0. 01;8 weeks:Hemin group (6. 50±0. 55) times vs VD group (4. 50±1. 05) times,t=4. 14,P<0. 01). The expression of Ngb and phosphorylated Tau (p-Tau) increased in VD group and Hemin group (P<0. 01). Compared with VD group,the expression of Ngb in Hemin group was increased(1 week:Hemin group (3. 45±0. 23) vs VD group (2. 56±0. 08),t=5. 67,P<0. 01;4 weeks:Hemin group (3. 08±0. 13) vs VD group (2. 28±0. 08),t=7. 96,P<0. 01;8 weeks:Hemin group (2. 82± 0. 12) vs VD group (2. 05±0. 10),t=7. 28,P<0. 01),while p-Tau was decreased (1 week:Hemin group (1. 57±0. 12) vs VD group (2. 40±0. 15),t=7. 62,P<0. 01;4 weeks:Hemin group ( 2. 14±0. 21) vs VD group (3. 18±0. 14),t=8. 23,P<0. 01;8 weeks:Hemin group (1. 83±0. 13) vs VD group (2. 79±0. 19), t=4. 91,P<0. 01). In VD group and Hemin group,the learning and memory ability exhibited a negative cor-relation with Ngb (r=-0. 892,P<0. 01),whereas a positive correlation with p-Tau (r=0. 932,P<0. 01). Conclusion Hemin induces high expression of Ngb and inhibits Tau phosphorylation in VD rats. Ngb may play a neuroprotective role in the development of VD by regulating Tau phosphorylation.
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As a newly discovered type of oxygen-carrying protein,neuroglobin(Ngb) is mainly presented in neurons in the form of monomers,which is closely related to oxygen supply in brain tissues.Neuronal apoptosis and necrosis caused by central nervous system injury aggravate the degrees of cerebral ischemia and hypoxia,and further induce the Ngb high expression,thus exerting a significant neuroprotective effect.As oxygen receptor and oxygen-carrying protein,Ngb can exert endogenous neuroprotective effects under hypoxic conditions and reduce the degree of hypoxic-ischemic brain damage.In this paper,we summarize the structure and function of Ngb,and explore the expression changes and mechanism of Ngb in various types of central nervous system injury.
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Neuroglobin (Ngb) is a globin with high affinity to oxygen and is specifically expressed in the brain of vertebrates.Many studies show that Ngb's expressions change and it may have protective effects in nervous system injury,such as ischemia/hypoxia.Mechanisms of the Ngb's protective role include free radicals scavenging,anti-oxidative stress,as well as anti-apoptosis.Ngb can also play a transduction signal to increase downstream phosphatidylinositol-3-kinase/protein serine threonine kinase (PI3K/AKT) signal activities.Arsenic exposure can lead to oxidative stress and apoptosis,Ngb may play a protective role in nervous system injury.In this article,we summarized expression changes and protective role of neuroglobin in nervous system injuries,and out looked the protective role of neuroglobin in endemic arsenic poisoning induced nervous system injury.
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Objective To study the protective effects of ulinastatin on brain tissue from pathomorphism and the changes of serum IL-6,Ngb (neuroglobin of brain),S100B protein and superoxide dismutase (SOD) after cardiopulmonary resuscitation (CPR) in swine.Methods The CPR model of swine was made by a programmed electric stimulation given to myocardium to produce a ventricular fibrillation and then a CPR was given.A flock of 16 male healthy Beijing landraces pigs of 3-4 months old were divided in random number method into control group (n =6) and ulinastatin group (n =6),because there were 12 swine survived from ventricular fibrillation.The t-test was used for the statistical analysis.ELISA was used to detect the changes in levels of those biomarkers in serum at each interval as well as the pathomorphological changes in brain tissues were observed under the light microscope after HE staining.Results (1) Before ventricular fibrillation,there were no distinct differences in levels of various biomarkers in porcine serum between two groups.After ventricular fibrillation,serum IL-6,S100B protein and Ngb levels in both groups gradually increased as time elapsed,and the levels of those biomarkers in the control were significantly higher than those in the ulinastatin group (P < 0.05).Serum SOD in both groups gradually reduced,and more distinct decline of biomarkers was found in the ulinastatin group (P < 0.05).(2) HE staining showed the porcine brain tissues in control group had significant ischemia,degeneration and necrosis and the degree of those pathological changes in the ulinastatin group were significantly moderated.Conclusion The immediate administration of ulinastatin as CPR initiated can alleviate porcine brain tissue damage after ischemia/reperfusion (I/R).This showed a protective effect of ulinastatin against I/R injury on porcine brain.
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Objective To investigate the role of neuroglobin ( NGB) in oxygen-glucose deprivation and reoxygenation ( OGD/R ) induced mitochondrial depolarization and reactive oxygen species ( ROS ) production in a human neuroblastoma cell line (SH-SY5Y).Methods SH-SY5Y cells were transfected with lentivirus to establish a stable cell line of NGB knockdown ( KD).After treated with OGD/R, cells were collected at different time points to analyze NGB mRNA and protein levels.Furthermore, cells were stained with JC-1 and DCFH-DA to evaluate mitochondrial depolarization and ROS production by inverted fluorescence microscope.Also, to determine the neurotoxicity , we measured the lactate dehydrogenase ( LDH) level in the cell culture medium.Results After the treatment of OGD/R, the NGB mRNA and protein started to elevate and peak at 4 h and 8 h (2.04 ±0.35 fold,1.69 ±0.18 fold).Compared with the vector group , NGB KD group had much more mitochondrial depolarization [ JC-1 red/green ( 1.10 ±0.10 ) vs (1.46 ±0.11),P<0.05] and ROS production [DCFH-DA fluorescence (36.30 ±5.32) vs (16.26 ± 2.97),P<0.05].Furthermore, NGB KD groups had a higher level of LDH release [(63.42 ±6.14)%vs (49.65 ±5.09 )%, P <0.05 ].Conclusions NGB plays an important role in the homeostasis of mitochondria.Knockdown of NGB results in increased mitochondrial depolarization , ROS production and neurotoxicity under hypoxia circumstances.
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Objective To observe the expression of neuroglobin in brain of rat with septic shock,and study the protective effect of neuroglobin.Methods Sixty male SD rats were randomly di-vided into two groups,30 rats in each.The rats in group M were injected LPS 10 mg/kg through tail vein to establish septic shock model,the success standard of septic shock was systolic blood pressure dropping to 60% of the basic values;the control group were given equal volume of NS.The levels of rat TNF-α,IL-6 and NGB in serum at the time points of before LPS injection (T0 ),1 h (T1 ),2 h (T2 ),4 h (T3 )and 6 h(T4 )after LPS injection were measured using ELISA kits.NGB and caspase-3 protein expression in brain were determined using Western blotting.Results Compared with group C and T0 ,the TNF-α,IL-6 concentrations in serum and caspase-3 in brain were increased significantly at T1-T4 (P <0.05),NGB protein content in serum and brain at T3 and T4 were increased significantly (P <0.05).Conclusion Cell apoptosis and inflammatory response are discovered in the brain during septic shock.NGB is over-expressed in brain of rats with septic shock,which may play a role of pro-tective function.
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Objective To observe the effects of sodium arsenite (NaAsO2) on apoptosis in primary cultured rat cerebellar granule cell and nerve globin mRNA expression.Methods Twenty 7-8 days postnatal Wistar rats were selected and decapitated cerebellar cortex, granular cell suspension was prepared and 4 × 109/m2 cells were seeded in the culture flask.Cells were exposed to different concentrations NaAsO2 [0 (control), 2, 5 and 10 μmol/L] for 24 h and intracellular reactive oxygen species (ROS) content and apoptosis were determined by laser confocal,while real-time quantitative PCR was used to detect mRNA expression in cultured cells after 24 and 48 h cell culture.Results Fluorescence intensity of ROS of 0, 2, 5, 10 μmol/L fluoride groups were 421.32 ± 53.52,1 082.09 ± 321.58, 2 223.02 ± 1 011.37 and 1 366.87 ± 102.14, the difference was statistically significant (F =5.873,P < 0.05);Apoptosis rates were (8.91 ± 5.63)%, (26.46 ± 1.77)%, (43.65 ± 14.45)% and (56.04 ± 6.95)%, the difference was statistically significant (F =18.369, P < 0.05);24 h nerve globin mRNA expression were 1.00 ± 0.06,0.77 ± 0.22, 0.43 ± 0.18 and 0.42 ± 0.14, the difference was statistically significant (F =18.235, P < 0.05);48 h nerve globin mRNA expression were 1.00 ± 0.01, 0.89 ± 0.09, 0.60 ± 0.16 and 0.08 ± 0.02, the difference was statistically significant (F =80.843, P < 0.05).Conclusion With increased NaAsO2 concentration, ROS and apoptosis levels are increased, while nerve globin mRNA expression is significantly reduced, suggesting that after the body is stimulated, protective proteins might be consumed, further suggesting nerve globin expression might be involved in nerve damage caused by arsenic.
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AIM:To observe the expression of hypoxia-inducible factor 1 (HIF-1) and neuroglobin (NGB) in piglet cortex during deep hypothermic circulatory arrest.METHODS:Wuzhishan piglets were randomly assigned to car-diopulmonary bypass group ( CPB group) , 40 min of circulatory arrest ( CA) at 18 ℃ without cerebral perfusion ( DHCA group) or with selective antegrade cerebral perfusion ( SACP group) .After 180 min of reperfusion, cortical tissue was har-vested for determining HIF-1αand NGB expression by HE staining, Western blot and real-time PCR.RESULTS:Severer cerebral injury was observed in DHCA group than that in SACP group.After 180 min of reperfusion, HIF-1αprotein and mRNA levels were significantly higher in DHCA group than those in CPB group (P<0.05).Accordingly, SACP animal had higher levels of HIF-1αprotein and mRNA than those in DHCA group (P<0.05).Simultaneously, higher NGB pro-tein and mRNA levels were found in DHCA group than those in CPB group after 180 min of reperfusion ( P<0.05) .The SACP animal had higher levels of NGB protein and mRNA than those in DHCA group (P<0.05).CONCLUSION:Up-regulation of HIF-1 and NGB are involved in the mechanism against cerebral injury resulting from DHCA in the cortex and possibly a part of cerebral protective effect of SACP.
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Objective To study the relationships of serum neuroglobin and neuron-specific enolase level with periventricular hemorrhage-intraventricular hemorrhage ( PVH-IVH) and periventricular leucumalacia ( PVL) in preterm infants. Methods There were 241 cases of preterm infants whose gestational age was less than 34 weeks and were admitted in NICU of Guangzhou Women and Children′s Medical Center, Guangzhou Huadu District Matermal and Child Health Hospital and Dongguan Taiping Hospital from Jan. 2010 to May. 2013, enrolled in the study. The serum level of neuroglobin and neuron-specific enolase were detected within 12 hours and on the 3 d, 7 d, 14 d after birth. Cranial ultrasound was preformed 2~3 d, 1week, 2weeks, 3weeks, and 4 weeks after birth. They also received Cranial MRI examination before discharge or when the correct gestational age reached 40 weeks. All 241 cases were divided into 3 groups ( no brain damage group, PVH-IVH group and PVL group) according to the result of cranial US and MRI. The differences of the serum levels of neuroglobin and neuron-specific enolase among each groups were compared. Results The results of cranial ultrasound and /or MRI showed: 162 cases had no brain damage ( in no brain damage group) , 50 cases had PVH-IVH ( in PVH-IVH group) , and 20 cases had PVL, 9 cases had PVL and PVH-IVH ( both in PVL group) . Within 12 h and 3 d after birth, the serum levels of neuroglobin in PVL group and PVH-IVH group was significantly higher than those in no brain damage group (P0. 05 ) , and there were still significantly higher than those in no brain damage group and PVH-IVH group (all P0. 05). On 7 d and 14 d after birth, the serum levels of neuron-specific enolase in PVL group were no significant difference compared with PVH-IVH group and no brain damage group (all P>0. 05). Conclusion The increased serum levels of neuroglobin and neuron-specific enolase in preterm infants within 12 h and 3 d after birth would have certain clinical significance for judging whether early brain damage and PVL would happen.