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1.
Neural Plast ; 2019: 6856327, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31093272

RESUMO

Tau hyperphosphorylation is a typical pathological change in Alzheimer's disease (AD) and is involved in the early onset and progression of AD. Epigenetic modification refers to heritable alterations in gene expression that are not caused by direct changes in the DNA sequence of the gene. Epigenetic modifications, such as noncoding RNA regulation, DNA methylation, and histone modification, can directly or indirectly affect the regulation of tau phosphorylation, thereby participating in AD development and progression. This review summarizes the current research progress on the mechanisms of epigenetic modification associated with tau phosphorylation.

2.
Zhongguo Zhen Jiu ; 39(3): 281-6, 2019 Mar 12.
Artigo em Chinês | MEDLINE | ID: mdl-30942016

RESUMO

OBJECTIVE: To observe the effects of acupuncture at "Baihui" (GV 20) and "Shenshu" (BL 23) on the ultrastructure of hippocampal dentate gyrus in rats with Alzheimer's disease. METHODS: Forty SPF Wistar male rats were randomly divided into a normal group, a sham operation group, a model group and an acupuncture group, 10 rats in each one. The rats in the model group and the acupuncture group were treated with injection of 5 µL Aß1-42 at bilateral hippocampus, while the rats in the sham operation group were treated with injection of 5 µL 0.9% NaCl. Three days after modeling, the rats in the acupuncture group were treated with acupuncture at "Baihui" (GV 20) and "Shenshu" (BL 23) for 20 min, once a day, six treatments constituted a course, and totally two courses were given with an interval of 1 day between courses. The rats in the other groups received normal diet and no treatment was given. Before modeling, four days after modeling and after treatment, water maze test was performed to observe the escape latency and the number of crossing platforms. The hippocampal dentate gyrus was collected and transmission electron microscope was applied to observe the ultrastructure changes of neurons and astrocytes. RESULTS: ①Four days after modeling, compared with the normal group and the sham operation group, the escape latency was significantly prolonged and the number of crossing platforms was reduced in the model group (all P<0.01); after treatment, compared with the model group, the escape latency was significantly reduced and the number of crossing platforms was increased in the acupuncture group (both P<0.01). ②In the normal group and the sham operation group, the morphology of neurons and astrocytes was intact, the nuclear and membrane structure were clear, and the morphology of organelles such as mitochondria, endoplasmic reticulum and lysosomes was normal. In the model group, the morphology of neurons was irregular, the nucleus was severely constricted with edema in the cytoplasm, the color of heterochromatin was deepened, the endoplasmic reticulum was expanded, the granulation was removed and the number of mitochondria was decreased, even with malformed-like change in mitochondrial cristae; there was severe edema around astrocytes, few organelles in the cytoplasm, severe swelling of mitochondria and mild expansion of the endoplasmic reticulum. In the acupuncture group, the edema of the neuron and astrocytes was still evident, and the mitochondrial was mildly swollen but relieved compared with that in the model group, and there were no obvious abnormalities in neuronal endoplasmic reticulum and ribosomes. CONCLUSION: Acupuncture could improve the ultrastructure of neurons and astrocytes in the hippocampal dentate gyrus in rats with Alzheimer's disease induced by Aß1-42.


Assuntos
Terapia por Acupuntura , Doença de Alzheimer , Peptídeos beta-Amiloides , Animais , Astrócitos , Giro Denteado , Hipocampo , Masculino , Neurônios , Fragmentos de Peptídeos , Ratos , Ratos Sprague-Dawley , Ratos Wistar
3.
Chin J Integr Med ; 2018 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-30155679

RESUMO

As the worldwide population ages, the prevalence of Alzheimer's disease (AD) increases. However, the results of promising medications have been unsatisfactory. Chinese acupuncture has a long history of treating dementia, but lack of evidence from well-designed randomized controlled trials that validate its efficacy and safety, as well as its lack of clear underlying mechanisms, contribute to its limited application in clinical practice. In recent years, brain imaging technologies, such as functional magnetic resonance imaging and positron emission tomography, have been used to assess brain responses to acupuncture in a dynamic, visual, and objective way. These techniques are frequently used to explore neurological mechanisms of responses to acupuncture in AD and provide neuroimaging evidence as well as starting points to elucidate the possible mechanisms. This review summarizes the existing brain imaging evidence that explains the effects of acupuncture for AD and analyzes brain responses to acupuncture at cognitive-related acupoints [Baihui (GV 20), Shenmen (HT 7), Zusanli (ST 36), Neiguan (PC 6), and Taixi (KI 3)] from perspectives of acupoint specificity and acupoint combinations. Key issues and directions to consider in future studies are also put forward. This review should deepen our understanding of how brain imaging studies can be used to explore the underlying mechanisms of acupuncture in AD.

4.
Neural Regen Res ; 13(10): 1833-1841, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30136700

RESUMO

Acupuncture has been shown to ameliorate cognitive impairment of Alzheimer's disease. Acupoints and stimulation frequency influence the therapeutic effect of electroacupuncture. Rat models of Alzheimer's disease were established by injecting amyloid beta 1-42 (Aß1-42) into the bilateral lateral ventricles. Electroacupuncture at 2, 30, and 50 Hz was carried out at Baihui (GV20; 15° obliquely to a depth of 2 mm) and Shenshu (BL23; perpendicularly to 4-6 mm depth), once a day for 20 minutes (each), for 15 days, taking a break every 7 days. The Morris water maze test was conducted to assess the learning and memory. The expression levels of glycogen synthase kinase-3ß (GSK-3ß), pSer9-GSK-3ß, pTyr216-GSK-3ß, amyloid precursor protein and Aß1-40 in the hippocampus were determined by western blot assay. Results demonstrated that electroacupuncture treatment at different frequencies markedly improved learning and memory ability, increased synaptic curvatures, decreased the width of synaptic clefts, thickened postsynaptic densities, and downregulated the expression of GSK-3ß, amyloid precursor protein, and Aß1-40. pSer9-GSK-3ß expression markedly decreased, while pTyr216-GSK-3ß expression increased. High-frequency (50 Hz) electroacupuncture was more effective than low (2 Hz) or medium-frequency (30 Hz) electroacupuncture. In conclusion, electroacupuncture treatment exerts a protective effect against Aß1-42-induced learning and memory deficits and synapse-ultrastructure impairment via inhibition of GSK-3ß activity. Moreover, high-frequency electroacupuncture was the most effective therapy.

5.
Neural Regen Res ; 11(5): 801-6, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27335565

RESUMO

The frequency range of electroacupuncture in treatment of Alzheimer's disease in rats is commonly 2-5 Hz (low frequency) and 50-100 Hz (high frequency). We established a rat model of Alzheimer's disease by injecting ß-amyloid 1-42 (Aß1-42) into the bilateral hippocampal dentate gyrus to verify which frequency may be better suited in treatment. Electroacupuncture at 2 Hz or 50 Hz was used to stimulate Baihui (DU20) and Shenshu (BL23) acupoints. The water maze test and electrophysiological studies demonstrated that spatial memory ability was apparently improved, and the ranges of long-term potentiation and long-term depression were increased in Alzheimer's disease rats after electroacupuncture treatment. Moreover, the effects of electroacupuncture at 50 Hz were better than that at 2 Hz. These findings suggest that high-frequency electroacupuncture may enhance hippocampal synaptic transmission and potentially improve memory disorders in Alzheimer's disease rats.

6.
Zhongguo Zhen Jiu ; 34(2): 157-62, 2014 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-24796053

RESUMO

OBJECTIVE: To observe effects of acupuncture and moxibustion on ultrastructure and silent information regulator 1 (SIR1) in hippocampal neuron mitochondria in rats with Alzheimer's disease (AD) in order to explore its possible effective mechanism during the process of protecting mitochondria. METHODS: Eighty Wistar rats were randomly divided into a normal group, a sham operation group, a model group and an acupuncture group, 20 rats in each one. The AD model was established in the model group and acupuncture group with injection of Amyloid beta Protein Fragment1-14 (Abeta1-42) into the hippocampus. Acupuncture and moxibustion was applied at "Baihui" (GV 20) and "Shenshu" (BL 23) in the acupuncture group, once a day, seven days as a treatment course and totally two course were required. The rest groups were all fed with normal diet, without any treatment. The transmission electron microscopy, immunohistochemistry and immunoblotting technique were respectively adapted to measure ultrastructure and level of STR1 in hippocampal neuron mitochondria in AD rats. RESULTS: Compared with the model group, the ultrastructure in hippocampal neuron mitochondria in the acupuncture group was effectively improved. The average optical density of SIR1 in hippocampus was 0.21 +/- 0.10 and the gray value was 136.82 +/- 47.42 in the model group, which were obviously lower than 0.47 +/- 0.09 and 281.44 +/- 57.98 in the normal group (both P < 0.01). However, levels of SIR1 in the acupuncture group, they were 0.32 +/- 0.11 and 199.52 +/- 58.12, which were significantly increased compared with those in the model group (both P < 0.05). CONCLUSION: The reinforcing-kidney and regulating-Governor Vessel method of acupuncture and moxibustion for AD could improve ultrastructure of mitochondria and increase levels of SIR1 to achieve the aim of recovering injury of mitochondria and protecting function of mitochondria.


Assuntos
Terapia por Acupuntura , Doença de Alzheimer/terapia , Hipocampo/citologia , Mitocôndrias/metabolismo , Moxibustão , Neurônios/metabolismo , Doença de Alzheimer/metabolismo , Doença de Alzheimer/prevenção & controle , Peptídeos beta-Amiloides/metabolismo , Animais , Hipocampo/metabolismo , Humanos , Masculino , Neurônios/citologia , Ratos , Ratos Wistar
7.
Zhen Ci Yan Jiu ; 35(6): 409-14, 2010 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-21375013

RESUMO

OBJECTIVE: To observe the effect of acupoint-embedement of medicated-thread and acupoint-injection of Chuanxiongzine on the expression of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) in the cerebral cortex in rats with cerebral ischemia-reperfusion injury (CI/RI), so as to explore its underlying mechanism in protecting the ischemic cerebral tissue. METHODS: Seventy-eight SD rats were randomly divided into normal control group (n=6), sham operation (sham) group (n=18), model group (n=18),acupoint injection (Al) group (n=18), and acupoint-thread-embedment (ATE) group (n=18). Rats of the latter 4 groups were randomized into 1 d, 3 d and 5 d subgroups, with 6 rats in each. CI/RI model was established by occlusion of the right middle cerebral artery (MCAO) for 30 min and reperfusion. For rats of the Al group, Chuanxiongzine (0.1 mL/200 g) was injected into "Baihui" (GV 20) and "Dazhui" (GV 14), and for those of ATE group, a piece of medicated thread containing collagen protein (extracted from the rat's tail tissue) and Chuanxiongzine + retarder was embedded into GV 20 and GV 14, respectively. The expression of uPA and PAI-1 in the cerebral cortex on the ischemia side was detected by immunohistochemistry. RESULTS: In comparison with the normal control group, the expression of uPA of the ischemia cerebral cortex on day 1, 3 and day 5 in the model group was increased significantly (P < 0.01), while the PAI-1 expression decreased remarkably in the model group (P < 0.01). Compared with the 3 time-points of the model group, cortical uPA expression levels at the 3 time-points in the Al group and those of day 3 and day 5 in the ATE group were down-regulated significantly (P < 0.01), whereas cortical PAI-1 expression levels at the 3 time-points in both AI and ATE groups up-regulated considerably (P < 0.05, P < 0.01). Comparison between AI and ATE groups showed that the expression levels of cortical uPA in the latter group on day 3 and day 5 were significantly lower than those of the former group (P < 0.05), whereas the cortical PAI-1 expression levels in the latter group on day 3 and day 5 were evidently higher than those of the former group (P < 0.05). But, cortical PAI-1 expression of the ATE group on day 1 was significantly lower than that of the AI group (P < 0.05). No significant differences were found between the AI and ATE groups in the expression level of cortical uPA on day 1 and between normal and sham groups in both uPA and PAI-1 expression levels at the 3 time-points (P > 0.05). CONCLUSION: Both AI and ATE can down-regulate cortical uPA expression and up-regulate cortical PAI-1 expression in rats with CI/RI, which may contribute to their protective effect in reducing cerebral ischemic injury.


Assuntos
Pontos de Acupuntura , Medicamentos de Ervas Chinesas/administração & dosagem , Inibidor 1 de Ativador de Plasminogênio/genética , Traumatismo por Reperfusão/tratamento farmacológico , Ativador de Plasminogênio Tipo Uroquinase/genética , Animais , Categute , Modelos Animais de Doenças , Feminino , Expressão Gênica , Humanos , Masculino , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Ativador de Plasminogênio Tipo Uroquinase/metabolismo
8.
Zhongguo Zhen Jiu ; 27(11): 839-42, 2007 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-18085149

RESUMO

OBJECTIVE: To probe into the bidirectional regulation of acupuncture in the rat with motility abnormality of the stomach and the nerve mechanism. METHODS: Adopting electrophysiological methods, the extracellular discharge signals of neuronic action in NTS were recorded with glass microelectrodes. The effects of acupuncture at "Zusanli" (ST 36), "Neiguan" (PC 6), "Zhongwan" (CV 12), "Qihai" (CV 6) on discharges of NTS neurons and intra-gastric pressure were observed in the rat at normal physiological state, and increase or reduction of gastric motility. RESULTS: Acupuncture at "Zusanli" (ST 36), "Neiguan" (PC 6) could significantly promote gastric motility of the rat at normal status, increase or reduction of gastric motion, while acupuncture at "Zhongwan" (CV 12), "Qihai" (CV 6) could significantly inhibit gastric motion. And acupuncture at all the above acupoints could activate discharges of NTS neurons. CONCLUSION: The bidirectional regulation effect of an acupoint does not certainly indicate that the same point has bidirectional regulation effect on an internal organs at different pathological states, while this may show synthetic action of different points which is a good regulation towards normal states and homeostasis.


Assuntos
Pontos de Acupuntura , Terapia por Acupuntura , Motilidade Gastrointestinal , Gastropatias/terapia , Animais , Masculino , Ratos , Ratos Sprague-Dawley , Núcleo Solitário/fisiologia , Gastropatias/fisiopatologia
9.
Zhen Ci Yan Jiu ; 32(5): 301-5, 2007 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-18050620

RESUMO

OBJECTIVE: To observe the effects of acupoint-embedding (AE) of collagen plus Tetramethylpyrazine and electroacupuncture (EA) on the contents of TNF-alpha and IL-6 in hippocampus tissue in rats with focal cerebral ischemia-reperfusion (CI-R) injury. METHODS: A total of 120 SD rats were randomly divided into normal control (n=8), sham operation (n=24), model (CI-R, n=24), EA (n=24) and AE (n=24) groups, and the later 4 groups were further divided into 24 h, 72 h and 120 h subgroups (time-points) separately, with 8 cases in each. CI-R model was established by middle cerebral artery occlusion (MCAO) and reperfusion. For animals of AE group, the medicinal thread consisting of collagen and Tetramethylpyrazine was implanted into "Dazhui" (GV14) and bilateral "Neiguan" (PC6), once daily. For rats of EA group, EA (120 cycles/min, 1 mA) was applied to GV14 and PC6 for 30 min, once daily. The contents of TNF-alpha and IL-6 in the hippocampus were detected by using radio-immunoassay after processing the tissue samples (homogenate, centrifuge). RESULTS: The contents of TNF-alpha and IL-6 in hippocampus tissue of model group at 24 h, 72 h and 120 h time-points were significantly higher than those of normal control and sham operation groups (P<0.05), while after EA and AE, the contents of TNF-alpha at the 3 time-points decreased significantly (P<0.05), and IL-6 contents at the same 3 time-points increased further and significantly (P<0.05). Comparison between EA and AE groups showed that the contents of TNF-alpha of the later group at 72 h and 120 h were significantly lower than those of EA group (P<0.05), while IL-6 contents of AE group were significantly higher than those of EA group at the same time-points (P<0.05). CONCLUSION: Both EA and AE of collagen and Tetramethylpyrazine can evidently lower TNF-alpha content and significantly raise IL-6 level in hippocampus in rats with cerebral ischemia/reperfusion injury and the effect of AE is significantly superior to that of EA, which may contribute to their protective effects on ischemic cerebral neurons.


Assuntos
Pontos de Acupuntura , Isquemia Encefálica/terapia , Colágeno/administração & dosagem , Eletroacupuntura , Hipocampo/química , Interleucina-6/análise , Pirazinas/administração & dosagem , Traumatismo por Reperfusão/terapia , Fator de Necrose Tumoral alfa/análise , Animais , Feminino , Masculino , Ratos , Ratos Sprague-Dawley
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