|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 1 | Calycosin improves cognitive function in a transgenic mouse model of Alzheimer's disease by activating the protein kinase C pathway显示文摘The major pathological changes in Alzheimer's disease are beta amyloid deposits and cognitive impairment. Calycosin is a typical phytoestrogen derived from radix astragali that binds to estrogen receptors to produce estrogen-like effects. Radix astragali Calycosin has been shown to relieve cognitive impairment induced by diabetes mellitus, suggesting calycosin may improve the cognitive function of Alzheimer's disease patients. The protein kinase C pathway is upstream of the mitogen-activated protein kinase pathway and exerts a neuroprotective effect by regulating Alzheimer's disease-related beta amyloid degradation. We hypothesized that calycosin improves the cognitive function of a transgenic mouse model of Alzheimer's disease by activating the protein kinase C pathway. Various doses of calycosin(10, 20 and 40 mg/kg) were intraperitoneally injected into APP/PS1 transgenic mice that model Alzheimer's disease. Calycosin diminished hippocampal beta amyloid, Tau protein, interleukin-1 beta, tumor necrosis factor-alpha, acetylcholinesterase and malondialdehyde levels in a dose-dependent manner, and increased acetylcholine and glutathione activities. The administration of a protein kinase C inhibitor, calphostin C, abolished the neuroprotective effects of calycosin including improving cognitive ability, and anti-oxidative and anti-inflammatory effects. Our data demonstrated that calycosin mitigated oxidative stress and inflammatory responses in the hippocampus of Alzheimer's disease model mice by activating the protein kinase C pathway, and thereby improving cognitive function. | Lei Song Xiaoping Li Xiao-xue Bai Jian Gao Chun-yan Wang | 2017 | Neural Regeneration Research2017，12，11： | 25 |
| 2 | Neuroprotection of aucubin in primary diabetic encephalopathy显示文摘Hippocampal neuronal apoptosis accompanied by impairment of cognitive function occurs in primary diabetic encephalopathy. In this study, we investigated the neuroprotective mechanism of the iridoid glycoside, aucubin, using rats (n=8). Diabetes mellitus was induced in the rats by intraperitoneal (i.p.) injection of streptozotocin (60 mg/kg body weight). After 65 d, half of the DM rats were administered aucubin (5 mg/kg; i.p.) for 15 d, yielding treatment DM+A. A third group of rats received no strepto- zotocin or aucibin, and served as controls (CON). Encephalopathy was assessed using Y-maze be- havioral testing. Rats were euthanized on Day 87, and hippocampi were excised for visual (light and transmission electron microscopic) and immunochemical (Western blot; immunohistochemical) as- sessments of the CA1 subfield for apoptosis and expression of regulatory proteins Bcl-2 and Bax. Treatment responses to all the parameters examined (body weight, plasma glucose, Y-maze error rates, pyramidal cell ultrastructure, proportions of apoptotic cells, levels of expression of Bcl-2 and Bax, and survivability of neuronal cells) were identical: there were highly significant differences between DM and CON groups (P<0.001), but the effects were significantly moderated (P<0.01) in DM+A compared with DM. These findings confirm the association of apoptosis with the encephalopathic effects of diabetes mellitus, and suggest a major role of the expression levels of Bcl-2 and Bax in the regulation of apop- totic cell death. All of the results suggest that aucubin could effectively inhibit apoptosis by modulating the expressions of Bcl-2 and Bax genes. | XUE HongYu1, JIN LiJi1,2, JIN Lei1, ZHANG Peng1, LI DanQing4, XIA YanQiu1, LU YaNan1 & XU YongPing1,3 1 Department of Bioscience and Biotechnology, Dalian University of Technology, Dalian 116024, China 2 State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, China 3 Dalian SEM Bioengineer and Biotech Ltd., Dalian 116024, China 4 The Second Affiliated Hospital, Dalian Medical University, Dalian 116024, China | 2008 | Science China(Life Sciences)2008，51，6： | 22 |
| 3 | Structural and functional damage to the hippocampal neurovascular unit in diabetes-related depression显示文摘Previous studies have shown that models of depression exhibit structural and functional changes to the neurovascular unit. Thus, we hypothesized that diabetes-related depression might be associated with damage to the hippocampal neurovascular unit. To test this hypothesis, neurons, astrocytes and endothelial cells were isolated from the brain tissues of rat embryos and newborn rats. Hippocampal neurovascular unit co-cultures were produced using the Transwell chamber co-culture system. A model of diabetes-related depression was generated by adding 150 mM glucose and 200 μM corticosterone to the culture system and compared with the neuron + astrocyte and astrocyte + endothelial cell co-culture systems. Western blot assay was used to measure levels of structural proteins in the hippocampal neurovascular unit co-culture system. Levels of basic fibroblast growth factor, angiogenic factor 1, glial cell line–derived neurotrophic factor, transforming growth factor β1, leukemia inhibitory factor and 5-hydroxytryptamine in the hippocampal neurovascular unit co-culture system were measured by enzyme-linked immunosorbent assay. Flow cytometry and terminal deoxynucleotidyl transferase(TdT)-mediated dUTP nick end labeling staining was used to assess neuronal apoptosis in the hippocampal neurovascular unit. The neurovascular unit triple cell co-culture system had better barrier function and higher levels of structural and secretory proteins than the double cell co-culture systems. In comparison, in the model of diabetes-related depression, the neurovascular unit was damaged with decreased barrier function, poor structural integrity and impaired secretory function. Moreover, neuronal apoptosis was markedly increased, and 5-hydroxytryptamine levels were reduced. These results suggest that diabetes-related depression is associated with structural and functional damage to the neurovascular unit. Our findings provide a foundation for further studies on the pathogenesis of diabetes-related depression. | Jian Liu Yu-Hong Wang Wei Li Lin Liu Hui Yang Pan Meng Yuan-Shan Han | 2019 | Neural Regeneration Research2019，14，2： | 20 |
| 4 | Modified constraint-induced movement therapy alters synaptic plasticity of rat contralateral hippocampus following middle cerebral artery occlusion显示文摘Modified constraint-induced movement therapy is an effective treatment for neurological and motor impairments in patients with stroke by increasing the use of their affected limb and limiting the contralateral limb.However,the molecular mechanism underlying its efficacy remains unclear.In this study,a middle cerebral artery occlusion(MCAO)rat model was produced by the suture method.Rats received modified constraint-induced movement therapy 1 hour a day for 14 consecutive days,starting from the 7^th day after middle cerebral artery occlusion.Day 1 of treatment lasted for 10 minutes at 2r/min,day 2 for 20 minutes at 2 r/min,and from day 3 onward for 20 minutes at 4 r/min.CatWalk gait analysis,adhesive removal test,and Y-maze test were used to investigate motor function,sensory function as well as cognitive function in rodent animals from the 1st day before MCAO to the 21^st day after MCAO.On the 21^st day after MCAO,the neurotransmitter receptor-related genes from both contralateral and ipsilateral hippocampi were tested by micro-array and then verified by western blot assay.The glutamate related receptor was shown by transmission electron microscopy and the glutamate content was determined by high-performance liquid chromatography.The results of behavior tests showed that modified constraint-induced movement therapy promoted motor and sensory functional recovery in the middle cerebral artery-occluded rats,but had no effect on cognitive function.The modified constraint-induced movement therapy upregulated the expression of glutamate ionotropic receptor AMPA type subunit 3(Gria3)in the hippocampus and downregulated the expression of the beta3-adrenergic receptor gene Adrb3 and arginine vasopressin receptor 1 A,Avprla in the middle cerebral artery-occluded rats.In the ipsilateral hippocampus,only Adra2 a was downregulated,and there was no significant change in Gria3.Transmission electron microscopy revealed a denser distribution the more distribution of postsynaptic glutamate receptor 2/3,which is an a-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor,within 240 nm of the postsynaptic density in the contralateral cornu ammonis 3 region.The size and distribution of the synaptic vesicles within 100 nm of the presynaptic active zone were unchanged.Western blot analysis showed that modified constraint-induced movement therapy also increased the expression of glutamate receptor 2/3 and brain-derived neurotrophic factor in the hippocampus of rats with middle cerebral artery occlusion,but had no effect on Synapsin I levels.Besides,we also found modified constraint-induced movement therapy effectively reduced glutamate content in the contralateral hippocampus.This study demonstrated that modified constraint-induced movement therapy is an effective rehabilitation therapy in middle cerebral artery-occluded rats,and suggests that these positive effects occur via the upregulation of the postsynaptic membrane a-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor expression.This study was approved by the Institutional Animal Care and Use Committee of Fudan University,China(approval No.201802173 S)on March 3,2018. | Bei-Yao Gao Dong-Sheng Xu Pei-Le Liu Ce Li Liang Du Yan Hua Jian Hu Jia-Yun Hou Yu-Long Bai | 2020 | Neural Regeneration Research2020，15，6： | 19 |
| 5 | Curculigoside facilitates fear extinction and prevents depression-like behaviors in a mouse learned helplessness model through increasing hippocampal BDNF显示文摘Curculigoside(CUR)is the main active component of traditional Chinese medicine Curculigoorchioides Gaertn(Xianmao in Chinese),which exhibits a variety of pharmacological activities.In this study we investigated the effects of CUR on fear extinaion and related depression-like behaviors in mice.In fear conditioning task,we found that administration of CUR(1.6,8,40 mg.kg^-1.d^-1,ip,for 7 days)did not affect memory consolidation,but CUR at higher doses(8,40mg·kg·d^-1)significantly facilitated fear extinction,especially on D3 and D4.Moreover,CUR administration significantly ameliorated the fear conditioning-induced depression-like behaviors,likely through promoting fear extinction.We showed that CUR increased the expression of brain-derived neurotrophic factor(BDNF)and phosphorylation of tropomyosin receptor kinase B(TrkB)in the hippocampus,and activated protein kinase B(Akt)-mammalian target of the rapamycin(mTOR)signaling pathway.Administration of the selective TrkB agonist 7,8-dihydroxyflavone(7,8-DHF,5 mg kg·d^-1,ip)also facilitated fear extinction,ameliorated depression-like behaviors.We established a mouse learned helplessness(LH)model to evaluate the antidepressant activity of CUR.The spatial memory was assessed in Morris water maze.We showed that LH-induced depression-like behaviors,including prolonged immobility times in forced swim and tail suspension tests as well as spatial memory impairments;LH also downregulated BDNF expression and the Akt-mTOR signaling pathway in the hippocampus.Administration of CUR(1.6,8,40 mg·kg^-1·d^-1,ip,for 14 days)or 7,8-DHF(5 mg·kg·d^-1,ip,for 3 days)prevented LH-induced depression-like behaviors and promoted BDNF expression and the Akt-mTOR signaling pathway.In conclusion,CUR can accelerate the fear memory extinction and ameliorate depression-like behaviors in mice via promoting BDNF expression and activating the Akt-mTOR signaling pathway in the hippocampus. | San-juan Yang Zhu-jin Song Xun-cui Wang Zheng-rong Zhang Sheng-bing Wu Guo-qi Zhu | 2019 | Acta Pharmacologica Sinica2019，40，10： | 17 |
| 6 | 大海马消化系统胚后发育的形态学及组织学研究显示文摘大海马Hippocampus kuda为卵胎生海洋硬骨鱼类。利用解剖和连续组织切片技术,对孵化后2、5、9日龄、1月龄和3月龄几个特殊时期大海马消化系统的形态和组织学特征进行了报道。结果表明,大海马仔鱼孵化后1日,其消化系统已经明显分化为口咽腔、食道、小肠、直肠以及肝胰脏、胆囊等器官,但是仔鱼仍然以内源与外源混合性营养为主,至5日龄仔鱼变为完全的外源性营养;仔鱼孵化后9日左右是大海马的死亡'临界点',其消化系统的组织结构更趋于复杂;1月龄大海马的消化系统在结构和功能上进一步完善,小肠前端呈'z'型结构,管壁变厚,纵、环肌发达,肝脏组织充满大部分体腔,但在小肠周围仍然不能辨认独立的胰脏实体结构;3月龄成海马已经有了成熟的消化系统组织结构,保证了最大限度地消化和吸收动物性饵料。整个胚后发育阶段大海马没有形成胃,鱼体的形态和组织结构的变化与食性的变化紧密适应。 | 林强 吕军仪 张彬 储霞玲 高永利 | 2007 | 热带海洋学报2007，26，6： | 16 |
| 7 | Glutamate receptor delocalization in postsynaptic membrane and reduced hippocampal synaptic plasticity in the early stage of Alzheimer's disease显示文摘Mounting evidence suggests that synaptic plasticity provides the cellular biological basis of learning and memory, and plasticity deficits play a key role in dementia caused by Alzheimer's disease. However, the mechanisms by which synaptic dysfunction contributes to the pathogenesis of Alzheimer's disease remain unclear. In the present study, Alzheimer's disease transgenic mice were used to determine the relationship between decreased hippocampal synaptic plasticity and pathological changes and cognitive-behavioral deterioration, as well as possible mechanisms underlying decreased synaptic plasticity in the early stages of Alzheimer's disease-like diseases. APP/PS1 double transgenic(5 XFAD; Jackson Laboratory) mice and their littermates(wild-type, controls) were used in this study. Additional 6-weekold and 10-week-old 5 XFAD mice and wild-type mice were used for electrophysiological recording of hippocampal dentate gyrus. For10-week-old 5 XFAD mice and wild-type mice, the left hippocampus was used for electrophysiological recording, and the right hippocampus was used for biochemical experiments or immunohistochemical staining to observe synaptophysin levels and amyloid beta deposition levels. The results revealed that, compared with wild-type mice, 6-week-old 5 XFAD mice exhibited unaltered long-term potentiation in the hippocampal dentate gyrus. Another set of 5 XFAD mice began to show attenuation at the age of 10 weeks, and a large quantity of amyloid beta protein was accumulated in hippocampal cells. The location of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor and N-methyl-D-aspartic acid receptor subunits in synaptosomes was decreased. These findings indicate that the delocalization of postsynaptic glutamate receptors and an associated decline in synaptic plasticity may be key mechanisms in the early onset of Alzheimer's disease. The use and care of animals were in strict accordance with the ethical standards of the Animal Ethics Committee of Capital Medical University,China on December 17, 2015(approval No. AEEI-2015-182). | Ning Li Yang Li Li-Juan Li Ke Zhu Yan Zheng Xiao-Min Wang | 2019 | Neural Regeneration Research2019，14，6： | 14 |
| 8 | Nerve growth factor pretreatment against glutamate-induced hippocampal neuronal injury Action mechanism of phosphatase and tensin homologue deleted on chromosome 10显示文摘BACKGROUND: Nerve growth factor (NGF) attenuates glutamate-induced injury to hippocampal neurons, and the human tumor suppressor gene phosphatase and tensin homologue deleted on chromosome 10 (PTEN) promotes neuronal apoptosis. However, effects of PTEN in NGF-mediated neuroprotection against glutamate excitotoxicity remain poorly understood. OBJECTIVE: To investigate the relationship between NGF inhibition of glutamate-induced injury and PTEN. DESIGN, TIME AND SETTING: The randomized, controlled, in vitro study was performed at the Department of Pathophysiology, Medical School of Nantong University, China from October 2007 to March 2008. MATERIALS: Glutamate, NGF, 4, 6-diamidino-2-phenyl-indolediacetate, 3-[4, 5-dimethylthiazol-2-yl]- 2, 5-diphenyl tetrazoliumbromide (MTT), and lactate dehydrogenase kit (Sigma, USA), fluorescence microscope and inverted phase contrast microscope (Olympus, Japan) were used in this study. METHODS: Hippocampal neurons were obtained from newborn (< 24 hours) Sprague Dawley rats and cultured for 7 days. The control group was not treated with any intervention factor, the glutamate group was treated with glutamate (0.2 mmol/L), and NGF groups were treated with NGF (10, 50, 100, and 200 μg/L, respectively) prior to glutamate treatment. MAIN OUTCOME MEASURES: The MTT and lactate dehydrogenase assays were applied to evaluate viability of hippocampal neurons. Morphological changes in hippocampal neurons were observed using an inverted phase-contrast microscope, and neuronal apoptosis was detected by 4, 6-diamidino-2-phenyl-indolediacetate staining. PTEN mRNA and protein expression were measured by reverse transcription-polymerase chain reaction and Western blot analysis, respectively. RESULTS: Glutamate (0.2 mmol/L) induced significantly decreased neuronal viability and greater lactate dehydrogenase efflux compared with the control group (P < 0.01). However, compared with the glutamate group, cell viability significantly increased and lactate dehydrogenase efflux decreased in the NGF group with increasing NGF concentrations (P < 0.05 or P < 0.01). The apoptotic ratio and PTEN mRNA and protein expression decreased in the NGF group compared with the glutamate group (P < 0.01). CONCLUSION: Pretreatment with NGF exerted neuroprotective effects against glutamate-induced injury, partially through inhibition of PTEN expression and neuronal apoptosis. | Yae Hu Jiahui Mao Yan Zhu Ailing Zhou | 2010 | Neural Regeneration Research2010，5，1： | 12 |
| 9 | Neural stem cells:mechanisms and modeling显示文摘In the adult brain,neural stem cells have been found in two major niches:the hippocampus and the olfactory bulb.Neurons derived from these stem cells contribute to learning,memory,and the autonomous repair of the brain under pathological conditions.Hence,the physi-ology of adult neural stem cells has become a signifi-cant component of research on synaptic plasticity and neuronal disorders.In addition,the recently developed induced pluripotent stem cell technique provides a powerful tool for researchers engaged in the patho-logical and pharmacological study of neuronal disor-ders.In this review,we briefly summarize the research progress in neural stem cells in the adult brain and in the neuropathological application of the induced pluripotent stem cell technique. | Jun Yao Yangling Mu Fred H.Gage | 2012 | Protein & Cell2012，3，4： | 12 |
| 10 | Tibolone modulates neuronal plasticity through regulating Tau, GSK3β/Akt/PI3K pathway and CDK5 p35/p25 complexes in the hippocampus of aged male mice显示文摘Aging is a key risk factor for cognitive decline and age-related neurodegenerative disorders. Also, an age-related decrease in sex steroid hormones may have a negative impact on the formation of neurofibrillary tangles(NFTs); these hormones can regulate Tau phosphorylation and the principal kinase GSK3β involved in this process. Hormone replacement therapy decreases NFTs, but it increases the risk of some types of cancer. However, other synthetic hormones such as tibolone(TIB) have been used for hormone replacement therapy. The aim of this work was to evaluate the long-term effects of TIB(0.01 mg/kg and 1 mg/kg, intragastrically for 12 weeks) on the content of total and hyperphosphorylated Tau(PHF-1) proteins and the regulation of GSK3β/Akt/PI3 K pathway and CDK5/p35/p25 complexes in the hippocampus of aged male mice. We observed that the content of PHF-1 decreased with TIB administration. In contrast, no changes were observed in the active form of GSK3β or PI3 K. TIB decreased the expression of the total and phosphorylated form of Akt while increased that of p110 and p85. The content of CDK5 was differentially modified with TIB: it was increased at low doses and decreased at high doses. When we analyzed the content of CDK5 activators, an increase was found on p35; however, the content of p25 decreased with administration of low dose of TIB. Our results suggest a possible mechanism of action of TIB in the hippocampus of aged male mice. Through the regulation of Tau and GSK3β/Akt/PI3 K pathway, and CDK5/p35/p25 complexes, TIB may modulate neuronal plasticity and regulate learning and memory processes. | Teresa Neri-Gomez Judith Espinosa-Raya Sofia Diaz Cintra Julia Segura-Uribe Sandra Orozco-Suarez Juan Manuel Gallardo Christian Guerra-Araiza | 2017 | Neural Regeneration Research2017，12，4： | 12 |
| 11 | Differentiating between Alzheimer’s disease, amnestic mild cognitive impairment, and normal aging via diffusion kurtosis imaging显示文摘Diffusion kurtosis imaging can be used to assess pathophysiological changes in tissue structure and to diagnose central nervous system diseases. However, its sensitivity in assessing hippocampal differences between patients with Alzheimer’s disease and those with amnestic mild cognitive impairment has not been characterized. Here, we examined 20 individuals with Alzheimer’s disease (11 men and 9 women, mean 73.2 ± 4.49 years), 20 with amnestic mild cognitive impairment (10 men and 10 women, mean 71.55 ± 4.77 years), and 20 normal controls (11 men and 9 women, mean 70.45 ± 5.04 years). We conducted diffusion kurtosis imaging, using a 3.0 T magnetic resonance scanner, to compare hippocampal differences among the three groups. The results demonstrated that the right hippocampal volume and bilateral mean kurtosis were remarkably smaller in individuals with Alzheimer’s disease compared with those with amnestic mild cognitive impairment and normal controls. Further, the mean kurtosis was lower in the amnestic mild cognitive impairment group compared with the normal control group. The mean diffusion in the left hippocampus was lower in the Alzheimer’s disease group than in the amnestic mild cognitive impairment and normal control groups, while the mean diffusion in the right hippocampus was lower in the Alzheimer’s disease group than in the normal control group. Fractional anisotropy was similar among the three groups. These results verify that bilateral mean kurtosis and mean diffusion are sensitive to the diagnosis of Alzheimer’s disease and amnestic mild cognitive impairment. This study was approved by the Ethics Review Board of Affiliated Sixth People’s Hospital of Shanghai Jiao Tong University, China on May 4, 2010 (approval No. 2010(C)-6). | Guo-Ping Song Ting-Ting Yao Dan Wang Yue-Hua Li | 2019 | Neural Regeneration Research2019，14，12： | 11 |
| 12 | Possible mechanisms of lycopene amelioration of learning and memory impairment in rats with vascular dementia显示文摘Oxidative stress is involved in the pathogenesis of vascular dementia. Studies have shown that lycopene can significantly inhibit oxidative stress;therefore, we hypothesized that lycopene can reduce the level of oxidative stress in vascular dementia. A vascular dementia model was established by permanent bilateral ligation of common carotid arteries. The dosage groups were treated with lycopene(50, 100 and 200 mg/kg) every other day for 2 months. Rats without bilateral carotid artery ligation were prepared as a sham group. To test the ability of learning and memory, the Morris water maze was used to detect the average escape latency and the change of search strategy. Hematoxylin-eosin staining was used to observe changes of hippocampal neurons. The levels of oxidative stress factors, superoxide dismutase and malondialdehyde, were measured in the hippocampus by biochemical detection. The levels of reactive oxygen species in the hippocampus were observed by dihydroethidium staining. The distribution and expression of oxidative stress related protein, neuron-restrictive silencer factor, in hippocampal neurons were detected by immunofluorescence histochemistry and western blot assays. After 2 months of drug administration,(1) in the model group, the average escape latency was longer than that of the sham group, and the proportion of straight and tend tactics was lower than that of the sham group, and the hippocampal neurons were irregularly arranged and the cytoplasm was hyperchromatic.(2) The levels of reactive oxygen species and malondialdehyde in the hippocampus of the model group rats were increased, and the activity of superoxide dismutase was decreased.(3) Lycopene(50, 100 and 200 mg/kg) intervention improved the above changes, and the lycopene 100 mg/kg group showed the most significant improvement effect.(4) Neuron-restrictive silencer factor expression in the hippocampus was lower in the sham group and the lycopene 100 mg/kg group than in the model group.(5) The above data indicate that lycopene 100 mg/kg could protect against the learning-memory ability impairment of vascular dementia rats. The protective mechanism was achieved by inhibiting oxidative stress in the hippocampus. The experiment was approved by the Animal Ethics Committee of Fujian Medical University, China(approval No. 2014-025) in June 2014. | Ning-Wei Zhu Xiao-Lan Yin Ren Lin Xiao-Lan Fan Shi-Jie Chen Yuan-Ming Zhu Xiao-Zhen Zhao | 2020 | Neural Regeneration Research2020，15，2： | 11 |
| 13 | DL-3-n-butylphthalide ameliorates diabetes-associated cognitive decline by enhancing PI3K/Akt signaling and suppressing oxidative stress显示文摘DL3-n-Butylphthalide(DLNBP),a small molecular compound extracted from the seeds of Ap/um graveo/ens Linn(Chinese celery),has been shown to exert neuroprotective effects due to its anti-inflammatory,anti-oxidative and anti-apoptotic activities.DL-NBP not only protects against ischemic cerebral injury,but also ameliorates vascular cognitive impairment in dementia patients including AD and PD.In the current study,we investigated whether and how DL-NBP exerted a neuroprotective effect against diabetes-associated cognitive decline(DACD)in db/db mice,a model of type-2 diabetes,db/db mice were orally administered DL-NBP(20,60,120 mg·kg^(-1)·d^(-1))for 8 weeks.Then the mice were subjected to behavioral test,their brain tissue was collected for morphological and biochemical analyses.We showed that oral administration of DL-NBP significantly ameliorated the cognitive decline with improved learning and memory function in Morris water maze testing.Furthermore,DL-NBP administration attenuated diabetes-induced morphological alterations and increased neuronal survival and restored the levels of synaptic protein PSD95,synaptophysin and synapsin-1 as well as dendritic density in the hippocampus,especially at a dose of 60 mg/kg.Moreover,we revealed that DL-NBP administration suppressed oxidative stress by upregulating Nrf2/HO-1 signaling,and increased brain-derived neurotrophic factor(BDNF)expression by activating PI3K/Akt/CREB signaling in the hippocampus.These beneficial effects of DL-NBP were observed in high glucose-treated PC12 cells.Our results suggest that DL-NBP may be a potential pharmacologic agent for the treatment of DACD. | Bei-ni Wang Cheng-biao Wu Zi-miao Chen Pei-pei Zheng Ya-qian Liu Jun Xiong Jing-yu Xu Pei-feng Li Abdullah Al Mamun Li-bing Ye Zhi-long Zheng Yan-qing Wu Jian Xiao Jian Wang | 2021 | Acta Pharmacologica Sinica2021，42，3： | 11 |
| 14 | Dynamic changes of behaviors, dentate gyrus neurogenesis and hippocampal miR-124 expression in rats with depression induced by chronic unpredictable mild stress显示文摘The depression-like behavior phenotype,neurogenesis in the dentate gyrus and miR-124 expression in the hippocampus are the focus of current research on the pathogenesis of depression and antidepressant therapy.The present study aimed to clarify the dynamic changes of depression-like behavior,dentate gyrus neurogenesis and hippocampal miR-124 expression during depression induced by chronic stress to reveal pathological features at different stages of depression and to further provide insight into depression treatment.Chronic unpredictable mild stress depression models were established by exposing Sprague-Dawley rats to various mild stressors,including white noise,thermal swimming,stroboscopic illumination,soiled cages,pairing with three other stressed animals,cold swimming,tail pinch,restraint and water and food deprivation.Chronic unpredictable mild stress model rats underwent dynamic observation from 1 to 8 weeks and were compared with a control group(normal feeding without any stressors).To observe changes in the depression-like behavior phenotype during chronic unpredictable mild stress-induced depression,a sucrose preference test was used to evaluate the degree of anhedonia.An open-field test was used to evaluate locomotor activity and anxiety status.Compared with the control group,chronic unpredictable mild stress rats lost weight but did not have a depression-like behavioral phenotype at 1-4 weeks.Chronic unpredictable mild stress rats presented decreased sucrose preference and locomotor activity at 5-8 weeks.In addition,chronic unpredictable mild stress rats did not have significant anxiety-like behavior during 1-8 weeks of modeling.To observe neurogenesis dysfunctions and changes in neuronal number in the dentate gyrus during chronic unpredictable mild stress-induced depression,markers(DCX and DCX/BrdU)of neural proliferation and differentiation and the neuronal marker NeuN were assessed by immunofluorescence.Compared with the control group,neurogenesis and the neuronal number in the dentate gyrus did not change from 2 to 6 weeks;however,neural proliferation and differentiation in the dentate gyrus decreased,and the number of neurons decreased until the eighth week in the chronic unpredictable mild stress group.Real-time quantitative reverse transcription polymerase chain reaction assays and fluorescence in situ hybridization were used to measure the expression of hippocampal miR-124 during chronic unpredictable mild stress-induced depression.The results showed that the expression of hippocampal miR-124 was unchanged during the first 4 weeks but increased from 5 to 6 weeks and decreased from 7 to 8 weeks compared with the control group.These findings indicate that during chronic unpredictable mild stress-induced depression,the behavioral phenotype,miR-124 expression in the hippocampus,neurogenesis in the dentate gyrus and neuronal numbers showed dynamic changes,which suggested that various pathological changes occur at different stages of depression.All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Guangzhou University of Chinese Medicine of China in March 2015. | Yun-Ling Huang Ning-Xi Zeng Jie Chen Jie Niu Wu-Long Luo Ping Liu Can Yan Li-Li Wu | 2020 | Neural Regeneration Research2020，15，6： | 10 |
| 15 | Antidepressant-Like Action of Single Facial Injection of Botulinum Neurotoxin A is Associated with Augmented 5-HT Levels and BDNF/ERK/CREB Pathways in Mouse Brain显示文摘The present study was designed to examine the therapeutic effects of Botulinum neurotoxin A(BoNT/A)on depression-like behaviors in mice and to explore the potential mechanisms.These results revealed that a single facial injection of BoNT/A induced a rapid and prolonged improvement of depression-like behaviors in naive and space-restriction-stressed(SRS)mice,reflected by a decreased duration of immobility in behavioral despair tests.BoNT/A significantly increased the 5-hydroxytryptamine(5-HT)levels in several brain regions,including the hippocampus and hypothalamus,in SRS mice.BoNT/A increased the expression of the N-methyl-Daspartate receptor subunits NR1 and NR2 B in the hippocampus,which were significantly decreased in SRS mice.Furthermore,BoNT/A significantly increased the expression of brain-derived neurotrophic factor(BDNF)in the hippocampus,hypothalamus,prefrontal cortex,and amygdala,which were decreased in SRS mice.Finally,BoNT/A transiently increased the levels of phosphorylated extracellular signal-regulated kinase(p-ERK)and cAMPresponse element binding protein(p-CREB),which were suppressed in the hippocampus of SRS mice.Collectively,these results demonstrated that BoNT/A treatment has antidepressant-like activity in mice,and this is associated with increased 5-HT levels and the activation of BDNF/ERK/CREB pathways in the hippocampus,supporting further investigation of BoNT/A therapy in depression. | Yang Li Jing Liu Xu Liu Cun-Jin Su Qi-Lin Zhang Zhi-Hong Wang Lei-Fang Cao Xue-Yan Guo Ya Huang Weifeng Luo Tong Liu | 2019 | Neuroscience Bulletin2019，35，4： | 10 |
| 16 | Inhibition of Rac1-dependent forgetting alleviates memory deficits in animal models of Alzheimer's disease显示文摘Accelerated forgetting has been identified as a feature of Alzheimer's disease(AD),but the therapeutic efficacy of the manipulation of biological mechanisms of forgetting has not been assessed in AD animal models.Ras-re-lated C3 botulinum toxin substrate 1(Rac1),a small GTPase,has been shown to regulate active forgetting in Drosophila and mice?Here,we showed that Rac1 activity is aberrantly elevated in the hippocampal tissues of AD patients and AD animal models.Moreover,amyloid-beta 42 could induce Rac1 activation in cultured cells.The elevation of Rac1 activity not only accelerated 6-hour spatial memory decay in 3-month-old APP/PS1 mice,but also significantly contributed to severe memory loss in aged APP/PS1 mice.A similar age-dependent Rac1 activity-based memory loss was also observed in an AD fly model.Moreover,inhibition of Rac1 activity could ameliorate cognitive defects and synaptic plasticity in AD animal models.Finally,two novel compounds,identified through behavioral screening of a randomly selected pool of brain permeable small molecules for their positive effect in rescuing memory loss in both fly and mouse models,were found to be capable of inhibiting Rac1 activity.Thus,multiple lines of evidence corroborate in supporting the idea that inhibition of Rac1 activity is effective for treating AD-related memory loss. | Wenjuan Wu Shuwen Du Wei Shi Yunlong Liu Ying Hu Zuolei Xie Xinsheng Yao Zhenyu Liu Weiwei Ma Lin Xu Chao Ma Yi Zhong | 2019 | Protein & Cell2019，10，10： | 10 |
| 17 | Icariin Improves Cognitive Impairment after Traumatic Brain Injury by Enhancing Hippocampal Acetylation显示文摘Objective: To examine the effect of icariin(ICA) on the cognitive impairment induced by traumatic brain injury(TBI) in mice and the underlying mechanisms related to changes in hippocampal acetylation level. Methods: The modified free-fall method was used to establish the TBI mouse model. Mice with post-TBI cognitive impairment were randomly divided into 3 groups using the randomised block method(n=7): TBI(vehicle-treated), low-dose(75 mg/kg) and high-dose(150 mg/kg) of ICA groups. An additional sham-operated group(vehicle-treated) was employed. The vehicle or ICA was administrated by gavage for 28 consecutive days. The Morris water maze(MWM) test was conducted. Acetylcholine(ACh) content, m RNA and protein levels of choline acetyltransferase(Ch AT), and protein levels of acetylated H3(Ac-H3) and Ac-H4 were detected in the hippocampus. Results: Compared with the sham-operated group, the MWM performance, hippocampal ACh content, m RNA and protein levels of Ch AT, and protein levels of Ac-H3 and Ac-H4 were significantly decreased in the TBI group(P<0.05). High-dose of ICA significantly ameliorated the TBI-induced weak MWM performance, increased hippocampal ACh content, and m RNA and protein levels of Ch AT, as well as Ac-H3 protein level compared with the TBI group(P<0.05). Conclusion: ICA improved post-TBI cognitive impairment in mice by enhancing hippocampal acetylation, which improved hippocampal cholinergic function and ultimately improved cognition. | ZHANG Zi-gang WANG Xin ZAI Jin-hai SUN Cai-hua YAN Bing-chun | 2018 | Chinese Journal of Integrative Medicine2018，24，5： | 9 |
| 18 | Migration of bone marrow progenitor cells in the adult brain of rats and rabbits显示文摘Neurogenesis takes place in the adult mammalian brain in three areas:Subgranular zone of the dentate gyrus(DG);subventricular zone of the lateral ventricle;olfactory bulb.Different molecular markers can be used to characterizethe cells involved in adult neurogenesis.It has been recently suggested that a population of bone marrow(BM)progenitor cells may migrate to the brain and differentiate into neuronal lineage.To explore this hypothesis,we injected recombinant SV40-derived vectors into the BM and followed the potential migration of the transduced cells.Long-term BM-directed gene transfer using recombinant SV40-derived vectors leads to expression of the genes delivered to the BM firstly in circulating cells,then after several months in mature neurons and microglial cells,and thus without central nervous system(CNS)lesion.Most of transgene-expressing cells expressed NeuN,a marker of mature neurons.Thus,BM-derived cells may function as progenitors of CNS cells in adult animals.The mechanism by which the cells from the BM come to be neurons remains to be determined.Although the observed gradual increase in transgene-expressing neurons over 16mo suggests that the pathway involved differentiation of BM-resident cells into neurons,cell fusion as the principal route cannot be totally ruled out.Additional studies using similar viral vectors showed that BM-derived progenitor cells migrating in the CNS express markers of neuronal precursors or immature neurons.Transgene-positive cells were found in the subgranular zone of the DG of the hippocampus 16 mo after intramarrow injection of the vector.In addition to cells expressing markers of mature neurons,transgene-positive cells were also positive for nestin and doublecortin,molecules expressed by developing neuronal cells.These cells were actively proliferating,as shown by short term BrdU incorporation studies.Inducing seizures by using kainic acid increased the number of BM progenitor cells transduced by SV40vectors migrating to the hippocampus,and these cells were seen at earlier time points in the DG.We show that the cell membrane chemokine receptor,CCR5,and its ligands,enhance CNS inflammation and seizure activity in a model of neuronal excitotoxicity.SV40-based gene delivery of RNAi targeting CCR5 to the BM results in downregulating CCR5 in circulating cells,suggesting that CCR5 plays an important role in regulating traffic of BM-derived cells into the CNS,both in the basal state and in response to injury.Furthermore,reduction in CCR5 expression incirculating cells provides profound neuroprotection from excitotoxic neuronal injury,reduces neuroinflammation,and increases neuronal regeneration following this type of insult.These results suggest that BM-derived,transgeneexpressing,cells can migrate to the brain and that they become neurons,at least in part,by differentiating into neuron precursors and subsequently developing into mature neurons. | Donnahue Dennie Jean-Pierre Louboutin David S Strayer | 2016 | World Journal of Stem Cells2016，8，4： | 9 |
| 19 | A Critical Time-Window for the Selective Induction of Hippocampal Memory Consolidation by a Brief Episode of Slow-Wave Sleep显示文摘Although extensively studied, the exact role of sleep in learning and memory is still not very clear. Sleep deprivation has been most frequently used to explore the effects of sleep on learning and memory, but the results from such studies are inevitably complicated by concurrent stress and distress. Furthermore, it is not clear whether there is a strict time-window between sleep and memory consolidation. In the present study we were able to induce time-locked slow-wave sleep(SWS) in mice by optogenetically stimulating GABAergic neurons in the parafacial zone(PZ), providing a direct approach to analyze the influences of SWS on learning and memory with precise time-windows. We found that SWS induced by light for 30 min immediately or 15 min after the training phase of the object-in-place task significantly prolonged the memory from 30 min to 6 h. However, induction of SWS 30 min after the training phase did not improve memory, suggesting a critical time-window between the induction of a brief episode of SWS and learning for memory consolidation.Application of a gentle touch to the mice during light stimulation to prevent SWS induction also failed to improve memory, indicating the specific role of SWS,but not the activation of PZ GABAergic neurons itself, in memory consolidation. Similar influences of light-induced SWS on memory consolidation also occurred for Y-maze spatial memory and contextual fear memory, but not for cued fear memory. SWS induction immediately before the test phase had no effect on memory performance, indicating that SWS does not affect memory retrieval. Thus, by induction of a brief-episode SWS we have revealed a critical time window for the consolidation of hippocampusdependent memory. | Yi Lu Zheng-Gang Zhu Qing-Qing Ma Yun-Ting Su Yong Han Xiaodong Wang Shumin Duan Yan-Qin Yu | 2018 | Neuroscience Bulletin2018，34，6： | 9 |
| 20 | Donepezil attenuates vascular dementia in rats through increasing BDNF induced by reducing HDAC6 nuclear translocation显示文摘Vascular dementia(VD)is the second most common dementia disease after Alzheimer’s diseases(AD)in the world.Donepezil is used to treat mild to moderate AD,and it has been shown to treat cognitive impairment and memory deficits caused by VD.However,the action mechanism of donepezil against VD has not been clarified.In this study,a bilateral common carotid artery occlusion(BCCAO)model was established in rats to simulate the pathology of VD.Two weeks after the surgery,the rats were administered donepezil(10 mg·kg^−1·d^−1,ig)for 3 weeks,and then subjected to behavioral tests.We showed that donepezil treatment significantly improved the performance of BCCAO rats in Morris Water Mazes test and Step-down test.Furthermore,we showed that donepezil treatment significantly attenuated neurodegeneration and restored the synapse dendritic spines density in cortex and hippocampus.We revealed that donepezil treatment significantly increased BDNF expression in cortex and hippocampus.Interestingly,donepezil treatment significantly decreased nuclear translocation of HDAC6 and the binding between HDAC6 and BDNF promoter IV in cortex,but not in the hippocampus.The attenuated neurodegeneration by donepezil in cortex and hippocampus might due to the reduced ROS levels and increased phosphorylation of AMPK,whereas increased phosphorylation of AKT was only detected in cortex.In conclusion,our results demonstrate that donepezil attenuates neurodegeneration in cortex and hippocampus via increasing BDNF expression;the regulation of donepezil on HDAC6 occurred in cortex,but not in the hippocampus.This study further clarifies the pharmacological mechanism of donepezil,while also emphasizes the promising epigenetic regulation of HDAC6. | Wen-xuan Jian Zhao Zhang Jia-hong Zhan Shi-feng Chu Ye Peng Ming Zhao Qi Wang Nai-hong Chen | 2020 | Acta Pharmacologica Sinica2020，41，5： | 9 |
您所在的机构暂未开通此部分的功能，请联系管理员