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1.
Astrocytes' roles in late-onset Alzheimer's disease(LOAD) promotion are important, since they survive soluble or fibrillar amyloid-β peptides(Aβs) neurotoxic effects, undergo alterations of intracellular and intercellular Ca2+ signaling and gliotransmitters release via the Aβ/α7-n ACh R(α7-nicotinic acetylcholine receptor) signaling, and overproduce/oversecrete newly synthesized Aβ42 oligomers, NO, and VEGF-A via the Aβ/Ca SR(calcium-sensing receptor) signaling. Recently, it was suggested that the NMDAR(N-methyl-D-aspartate receptor) inhibitor nitromemantine would block the synapse-destroying effects of Aβ/α7-n ACh R signaling. Yet, this and the progressive extracellular accrual and spreading of Aβ42 oligomers would be stopped well upstream by NPS 2143, an allosteric Ca SR antagonist(calcilytic).  相似文献   

2.
《中国神经再生研究》2016,(9):1492-1498
The principal pathology of Alzheimer's disease includes neuronal extracellular deposition of amyloid-beta peptides and formation of senile pl aques,which in turn induce neuroinflammation in the brain.Triptolide,a natural extract from the vine-like herb Tripterygium wilfordii Hook F,has potent anti-inflammatory and immunosuppressive efficacy.Therefore,we determined if triptolide can inhibit activation and proliferation of microglial cells and astrocytes in the APP/PS1 double transgenic mouse model of Alzheimer's disease.We used 1 or 5 μg/kg/d triptolide to treat APP/PS1 double transgenic mice(aged 4–4.5 months) for 45 days.Unbiased stereology analysis found that triptolide dose-dependently reduced the total number of microglial cells,and transformed microglial cells into the resting state.Further,triptolide(5 μg/kg/d) also reduced the total number of hippocampal astrocytes.Our in vivo test results indicate that triptolide suppresses activation and proliferation of microglial cells and astrocytes in the hippocampus of APP/PS1 double transgenic mice with Alzheimer's disease.  相似文献   

3.
《中国神经再生研究》2016,(10):1617-1624
Impaired hippocampal neurogenesis is one of the early pathological features of Alzheimer's disease. Enhancing adult hippocampal neurogenesis has been pursued as a potential therapeutic strategy for Alzheimer's disease. Recent studies have demonstrated that environmental novelty activates β2-adrenergic signaling and prevents the memory impairment induced by amyloid-β oligomers. Here, we hypothesized that β2-adrenoceptor activation would enhance neurogenesis and ameliorate memory deficits in Alzheimer's disease. To test this hypothesis, we investigated the effects and mechanisms of action of β2-adrenoceptor activation on neurogenesis and memory in amyloid precursor protein/presenilin 1(APP/PS1) mice using the agonist clenbuterol(intraperitoneal injection, 2 mg/kg). We found that β2-adrenoceptor activation enhanced hippocampal neurogenesis, ameliorated memory deficits, and increased dendritic branching and the density of dendritic spines. These effects were associated with the upregulation of postsynaptic density 95, synapsin 1 and synaptophysin in APP/PS1 mice. Furthermore, β2-adrenoceptor activation decreased cerebral amyloid plaques by decreasing APP phosphorylation at Thr668. These findings suggest that β2-adrenoceptor activation enhances neurogenesis and ameliorates memory deficits in APP/PS1 mice.  相似文献   

4.
In our previous studies,we have shown that(D-Ser2)oxyntomodulin(Oxm),a glucagon-like peptide 1(GLP-1)receptor(GLP1R)/glucagon receptor(GCGR)dual agonist peptide,protects hippocampal neurons against Aβ1-42-induced cytotoxicity,and stabilizes the calcium homeostasis and mitochondrial membrane potential of hippocampal neurons.Additionally,we have demonstrated that(D-Ser2)Oxm improves cognitive decline and reduces the deposition of amyloid-beta in Alzheimer’s disease model mice.However,the protective mechanism remains unclear.In this study,we showed that 2 weeks of intraperitoneal administration of(D-Ser2)Oxm ameliorated the working memory and fear memory impairments of 9-month-old 3×Tg Alzheimer’s disease model mice.In addition,electrophysiological data recorded by a wireless multichannel neural recording system implanted in the hippocampal CA1 region showed that(D-Ser2)Oxm increased the power of the theta rhythm.In addition,(D-Ser2)Oxm treatment greatly increased the expression level of synaptic-associated proteins SYP and PSD-95 and increased the number of dendritic spines in 3×Tg Alzheimer’s disease model mice.These findings suggest that(D-Ser2)Oxm improves the cognitive function of Alzheimer’s disease transgenic mice by recovering hippocampal synaptic function and theta rhythm.  相似文献   

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