-
[show abstract]
[hide abstract]
ABSTRACT: There is no effective drug to treat Alzheimer's disease (AD), a neurodegenerative disease affecting an estimated 30 million people around the world. Strongly supported by preclinical and clinical studies, amyloid-beta (Aβ) may be a target for developing drugs against AD. Meanwhile, the fact that localized neuronal death/loss and synaptic impairment occur in AD should also be considered. Neuronal regeneration, which does not occur normally in the mammalian central nervous system, can be promoted by neurotrophic factors (NTFs). Evidence from clinical trials has shown that both Aβ clearance and NTFs are potentially effective in treating AD, thus a new approach combining Aβ clearance and administration of NTFs may be an effective therapeutic strategy.
Neuroscience Bulletin 11/2012; · 1.31 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To investigate the mechanisms underlying protocatechuic acid (PCA)-induced neurotrophic effects on cultured cortical neurons.
The mRNA expression of microtubule-associated protein 2 (MAP2) and brain-derived neurotrophic factor (BDNF) were measured by real-time quantitative PCR (qPCR). Subsequently, antagonists were used to study the signaling pathways activated by PCA and western blotting was used to detect the phosphorylation level of kinase-related protein.
The mRNA expression of MAP2 and BDNF were upregulated in neurons treated with PCA compared with vehicle control. PCA-induced neurite outgrowth and neuronal survival in cultured cortical neurons were significantly inhibited by ZM241385 (an A(2A) receptor antagonist) and LY294002 (a PI3K inhibitor), but not by K252a (a TrkA receptor antagonist), GÖ6976 (a protein kinase C inhibitor) and PD98059 (a MEK inhibitor). PCA enhanced the phosphorylation of Akt, which could be blocked by LY294002.
The PI3K/Akt signaling pathway might play an important role in the neurotrophic activity of PCA.
Neurological Research 08/2012; 34(9):901-7. · 1.52 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Chronic exposure to stress hormones might impair cognitive functions such as learning and memory, which were associated with many mood disorders and neurodegenerative diseases. In this study, we aimed to screen for effective compounds to prevent cognitive deficits induced by chronic stress. Daphnetin was found to protect the cortical neurons against dexamethasone-induced reduction of cell viability in a dose-dependent manner in vitro. We further evaluated its effects on chronic unpredictable stress (CUS) mice in vivo. Two and 8 mg/kg administration of daphnetin could improve the performance of stress mice in Morris water maze tests and forced swimming tests. The results suggested that daphnetin might be a potent compound to treat cognitive deficits induced by CUS.
Fundamental and Clinical Pharmacology 06/2012; · 1.80 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: ObjectiveIt has been reported that D-galactose (D-gal) can model subacute aging, and aluminum (Al) acts as a neurotoxin, but combined effects of them have not been reported.
The present work aimed to reveal the effect of combined administration of D-gal and Al in mice and compare the effect of D-gal treatment with that of Al treatment.
MethodsAl was intragastrically administered and D-gal was subcutaneously injected into Kunming mice for 10 consecutive weeks. Learning and memory, cholinergic systems, as
well as protein levels of amyloid β (Aβ) and hyperphosphorylated tau were determined using Morri water maze test, biochemical
assays and immunohistochemical staining, respectively.
ResultsThe mice with combined treatment had obvious learning and memory deficits, and showed decreases in brain acetylcholine (ACh)
level and in activities of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE). Formation of senile plaque (SP)-like
and neurofibrillary tangle (NFT)-like structures was also observed. The behavioral and pathological changes persisted for
at least 6 weeks after withdrawal of D-gal and Al.
ConclusionCombined use of D-gal and Al is an effective way to establish the non-transgenic Alzheimer’s disease (AD) animal model, and is useful for studies
of AD pathogenesis and therapeutic evaluation.
目的
D-半乳糖能制作亚急性衰老模型, 铝具有神经毒性, 但两者联合应用的作用未见报道。 本研究旨在探讨D-半乳糖和铝联合应用对动物学习记忆、 脑内生化和病理的影响, 以及与单独应用D-半乳糖或铝所制作的动物模型相比较。
方法|昆明小鼠单独皮下注射D-半乳糖、 单独灌胃铝以及既注射D-半乳糖又灌胃铝, 制作动物模型, 共给药8周或10周, 10周后再停用药物6周。 在第8、 10、 16周末, 采用Morris水迷宫检测小鼠学习记忆能力, 生化学方法检测脑内乙酰胆碱能系统, 免疫组化法检测老年斑和神经原纤维缠结的形成。
结果联合应用D-半乳糖和铝后, 小鼠表现出明显的学习和记忆力障碍, 并且其脑内乙酰胆碱水平降低, 乙酰胆碱转移酶和胆碱脂酶活性下降, 出现老年斑样和神经原纤维缠结样病理改变。 停止给药后, 其行为学、 生化和病理改变至少能维持6周以上。
结论小鼠中D-半乳糖和铝联合应用是一个有效的非转基因阿尔茨海默病(Alzheimer’s disease, AD)模型, 可用于AD病理研究和相关治疗药物的评价。
KeywordsAlzheimer’s disease–brain change–
D-galactose–aluminum–neurodegenerative disease–animal model
关键词阿尔茨海默病–脑改变–
D-半乳糖–铝–神经退行性疾病–动物模型
Neuroscience Bulletin 04/2012; 27(3):143-155. · 1.31 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: β-Amyloid (Aβ) over-expression and tau hyperphosphorylation are considered to be the central events in the pathogenesis of
Alzheimer’s disease (AD). Studies on them may help elucidate the precise molecular pathogenesis of AD. Until now, although
tau protein and Aβ remain the foci of AD research, the etiopathogenesis of AD and effective drugs for AD treatment are still
largely unsolved. The present review was mainly focused on the molecular mechanism of Aβ aggregation-related impairment and
the pathways leading to tau hyperphosphorylation, based on which some promising therapeutic targets for AD were also proposed.
阿尔茨海默病(Alzheimer’s disease, AD)的发病机制主要包括Aβ蛋白表达增高在脑内聚集形成老年斑和tau蛋白过度磷酸化在胞内形成神经原纤维缠结。 尽管Aβ与tau蛋白的损伤机制一直是AD研究的重点, 但目前仍未找到能有效治疗AD
的药物。 本文主要概述了Aβ蛋白聚集与tau蛋白过度磷酸化对大脑损伤作用的分子机制, 并从中寻找治疗AD的潜在靶点, 有助于阐明AD发病机理以及寻找有效的AD治疗药物。
KeywordsAlzheimer’s disease–Aβ aggregation–tau hyperphosphorylation–treatment targets
关键词阿尔茨海默病–Aβ聚集–tau蛋白过度磷酸化–治疗靶点
Neuroscience Bulletin 04/2012; 27(1):53-60. · 1.31 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: In this study, we evaluated the neurotrophic effects of magnesium fructose 1, 6-diphosphate (FDP-Mg) on cortical neurons. The results demonstrated that FDP-Mg promoted dendrite outgrowth and neuronal survival in a dose-dependent manner. In order to investigate the associated mechanisms, we determined adenosine triphosphate (ATP) levels and brain-derived neurotrophic factor (BDNF) mRNA expression in cortical neurons. Treatment with FDP-Mg significantly increased ATP levels and BDNF mRNA expression in cortical neurons. These data suggest that FDP-Mg can exert neurotrophic effects on cortical neurons. The increases in BDNF mRNA expression and cellular ATP levels are involved in the neurotrophic effects produced by FDP-Mg.
The International journal of neuroscience 12/2011; 122(5):248-54. · 0.86 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A Nogo-A to Nogo-66 receptor (NgR) pathway is well known to contribute to the inhibition of the neurite regeneration of adult central nervous system neurons after traumatic injuries. Recent evidence suggests that Nogo-A and NgR are involved in the pathology of Alzheimer's disease (AD), as evidenced by the fact that Nogo-A is overexpressed by hippocampal neurons in patients with AD and is associated with β-amyloid protein (Aβ) deposits in senile plaques. In the present experiments, we investigated the potential role of Nogo-A in both neurite outgrowth and Aβ generation in cortical neurons. Our results showed that activation of NgR not only inhibited neurite outgrowth in cortical neurons by activating the rho-associated coiled coil-containing protein kinase (ROCK) and protein kinase C, but also promoted their Aβ secretion, which was at least in part activated by ROCK. These findings suggest that the overexpression of Nogo-A and the activation of NgR inhibit neurite outgrowth and alter neuronal metabolism, resulting in overproduction and/or release of Aβ, which in turn may trigger the onset and development of AD. Inhibition of ROCK can promote neurite outgrowth and reduce Aβ production of cortical neuron, which suggests that ROCK appears to be a good target for AD therapy.
Molecular Medicine Reports 12/2011; 5(3):619-24. · 0.42 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: It has been reported that D-galactose (D-gal) can model subacute aging, and aluminum (Al) acts as a neurotoxin, but combined effects of them have not been reported. The present work aimed to reveal the effect of combined administration of D-gal and Al in mice and compare the effect of D-gal treatment with that of Al treatment.
Al was intragastrically administered and D-gal was subcutaneously injected into Kunming mice for 10 consecutive weeks. Learning and memory, cholinergic systems, as well as protein levels of amyloid β (Aβ) and hyperphosphorylated tau were determined using Morri water maze test, biochemical assays and immunohistochemical staining, respectively.
The mice with combined treatment had obvious learning and memory deficits, and showed decreases in brain acetylcholine (ACh) level and in activities of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE). Formation of senile plaque (SP)-like and neurofibrillary tangle (NFT)-like structures was also observed. The behavioral and pathological changes persisted for at least 6 weeks after withdrawal of D-gal and Al.
Combined use of D-gal and Al is an effective way to establish the non-transgenic Alzheimer's disease (AD) animal model, and is useful for studies of AD pathogenesis and therapeutic evaluation.
Neuroscience Bulletin 06/2011; 27(3):143-55. · 1.31 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To explore the effect and mechanism of ferulic acid on differentiation in bFGF-treated PC12 cells.
The length of neurite outgrowth and the percentage of PC12 cells induced in the presence of 0 ng/mL or 1 ng/mL bFGF were assayed.
Compared with that of control group,ferulic acid could enhance the differentiation effect of bFGF (1 ng/mL) in PC12 cells (P < 0.01) and the enhancing effect could be blocked by the specific MAPK kinase inhibitor, PD98059.
Ferulic acid potentiates neurite outgrowth in bFGF-treated PC12 cells by MAPK-dependent signaling pathway.
Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials 04/2011; 34(4):572-5.
-
[show abstract]
[hide abstract]
ABSTRACT: To study the neurotrophic effects of protocatechuic acid on neurite outgrowth and survival in cultured cerebral cortical neurons.
The newborn rat cerebral cortex neurons were cultured in vitro. The convert phase microscope was used to count the survival neurons with neurites and measure the average length of neurites. MTT and LDH assay were carried out to investigate the effect of PCA on the neuronal viability.
Compared with control group, different concentration of PCA could increase the number of survival neurons with neurites and the average length of neurites. MTT and LDH assay showed that PCA promoted neuron survival in a dose-dependent manner.
PCA can enhance the survival of rat cortical neurons with neurites and promote the neurite outgrowth of rat cortical neurons.
Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials 04/2011; 34(4):567-72.
-
[show abstract]
[hide abstract]
ABSTRACT: β-Amyloid (Aβ) over-expression and tau hyperphosphorylation are considered to be the central events in the pathogenesis of Alzheimer's disease (AD). Studies on them may help elucidate the precise molecular pathogenesis of AD. Until now, although tau protein and Aβ remain the foci of AD research, the etiopathogenesis of AD and effective drugs for AD treatment are still largely unsolved. The present review was mainly focused on the molecular mechanism of Aβ aggregation-related impairment and the pathways leading to tau hyperphosphorylation, based on which some promising therapeutic targets for AD were also proposed.
Neuroscience Bulletin 02/2011; 27(1):53-60. · 1.31 Impact Factor
