OBJECTIVE:To discuss the influence of Sailuotong(塞络通,SLT)on the Neurovascular Unit(NVUs)of amyloid precursor protein(APP)/presenilin-1(PS1)mice and evaluate the role of gas supplementation in activating blood circu...OBJECTIVE:To discuss the influence of Sailuotong(塞络通,SLT)on the Neurovascular Unit(NVUs)of amyloid precursor protein(APP)/presenilin-1(PS1)mice and evaluate the role of gas supplementation in activating blood circulation during the progression of Alzheimer's disease(AD).METHODS:The mice were allocated into the following nine groups:(a)the C57 Black(C57BL)sham-operated group(control group),(b)ischaemic treatment in C57BL mice(the C57 ischaemic group),(c)the APP/PS1 sham surgery group(APP/PS1 model group),(d)ischaemic treatment in APP/PS1 mice(APP/PS1 ischaemic group),(e)C57BL mice treated with aspirin following ischaemic treatment(C57BL ischaemic+aspirin group),(f)C57BL mice treated with SLT following ischaemic treatment(C57BL ischaemic+SLT group),(g)APP/PS1 mice treated with SLT(APP/PS1+SLT group),(h)APP/PS1 mice treated with donepezil hydrochloride following ischaemic treatment(APP/PS1 ischaemic+donepezil hydrochloride group)and(i)APP/PS1 mice treated with SLT following ischaemic treatment(APP/PS1 ischaemic+SLT group).The ischaemic model was established by operating on the bilateral common carotid arteries and creating a microembolism.The Morris water maze and step-down tests were used to detect the spatial behaviour and memory ability of mice.The hippocampus of each mouse was observed by haematoxylin and eosin(HE)and Congo red staining.The ultrastructure of NVUs in each group was observed by electron microscopy,and various biochemical indicators were detected by enzymelinked immunosorbent assay(ELISA).The protein expression level was detected by Western blot.The mRNA expression was detected by quantitative real-time polymerase chain reaction(qRT-PCR).RESULTS:The results of the Morris water maze and step-down tests showed that ischemia reduced learning and memory in the mice,which were restored by SLT.The results of HE staining showed that SLT restored the pathological changes of the NVUs.The Congo red staining results revealed that SLT also improved the scattered orange-red sediments in the upper cortex a展开更多
Extracellular amyloid beta(Aβ) plaques are main pathological feature of Alzheimer’s disease.However,the specific type of neuro ns that produce Aβ peptides in the initial stage of Alzheimer’s disease are unknown.In...Extracellular amyloid beta(Aβ) plaques are main pathological feature of Alzheimer’s disease.However,the specific type of neuro ns that produce Aβ peptides in the initial stage of Alzheimer’s disease are unknown.In this study,we found that 5-hydroxytryptamin receptor 3A subunit(HTR3A) was highly expressed in the brain tissue of transgenic amyloid precursor protein and presenilin-1 mice(an Alzheimer’s disease model) and patients with Alzheimer’s disease.To investigate whether HTR3A-positive interneurons are associated with the production of Aβ plaques,we performed double immunostaining and found that HTR3A-positive interneurons were clustered around Aβ plaques in the mouse model.Some amyloid precursor protein-positive or β-site amyloid precursor protein cleaving enzyme-1-positive neurites near Aβ plaques were co-localized with HTR3A interneurons.These results suggest that HTR3A-positive interneurons may partially contribute to the generation of Aβ peptides.We treated 5.0-5.5-month-old model mice with tro pisetron,a HTR3 antagonist,for 8 consecutive weeks.We found that the cognitive deficit of mice was partially reversed,Aβ plaques and neuroinflammation we re remarkably reduced,the expression of HTR3 was remarkably decreased and the calcineurin/nuclear factor of activated T-cell 4 signaling pathway was inhibited in treated model mice.These findings suggest that HTR3A interneurons partly contribute to generation of Aβ peptide at the initial stage of Alzheimer’s disease and inhibiting HTR3 partly reve rses the pathological changes of Alzheimer’s disease.展开更多
基金National Natural Science Foundation of China(81503450):Experimental study on the treatment of transgenic mice with Alzheimer's disease by protecting neurovascular unit by supplementing Qi and activating blood circulation investigate。
文摘OBJECTIVE:To discuss the influence of Sailuotong(塞络通,SLT)on the Neurovascular Unit(NVUs)of amyloid precursor protein(APP)/presenilin-1(PS1)mice and evaluate the role of gas supplementation in activating blood circulation during the progression of Alzheimer's disease(AD).METHODS:The mice were allocated into the following nine groups:(a)the C57 Black(C57BL)sham-operated group(control group),(b)ischaemic treatment in C57BL mice(the C57 ischaemic group),(c)the APP/PS1 sham surgery group(APP/PS1 model group),(d)ischaemic treatment in APP/PS1 mice(APP/PS1 ischaemic group),(e)C57BL mice treated with aspirin following ischaemic treatment(C57BL ischaemic+aspirin group),(f)C57BL mice treated with SLT following ischaemic treatment(C57BL ischaemic+SLT group),(g)APP/PS1 mice treated with SLT(APP/PS1+SLT group),(h)APP/PS1 mice treated with donepezil hydrochloride following ischaemic treatment(APP/PS1 ischaemic+donepezil hydrochloride group)and(i)APP/PS1 mice treated with SLT following ischaemic treatment(APP/PS1 ischaemic+SLT group).The ischaemic model was established by operating on the bilateral common carotid arteries and creating a microembolism.The Morris water maze and step-down tests were used to detect the spatial behaviour and memory ability of mice.The hippocampus of each mouse was observed by haematoxylin and eosin(HE)and Congo red staining.The ultrastructure of NVUs in each group was observed by electron microscopy,and various biochemical indicators were detected by enzymelinked immunosorbent assay(ELISA).The protein expression level was detected by Western blot.The mRNA expression was detected by quantitative real-time polymerase chain reaction(qRT-PCR).RESULTS:The results of the Morris water maze and step-down tests showed that ischemia reduced learning and memory in the mice,which were restored by SLT.The results of HE staining showed that SLT restored the pathological changes of the NVUs.The Congo red staining results revealed that SLT also improved the scattered orange-red sediments in the upper cortex a
基金supported by the Notional Natural Science Foundation of China,Nos.81371213 and 8107098 7the Natural Science Foundation of Shanghai,No.21ZR1468400 (all to QLY)。
文摘Extracellular amyloid beta(Aβ) plaques are main pathological feature of Alzheimer’s disease.However,the specific type of neuro ns that produce Aβ peptides in the initial stage of Alzheimer’s disease are unknown.In this study,we found that 5-hydroxytryptamin receptor 3A subunit(HTR3A) was highly expressed in the brain tissue of transgenic amyloid precursor protein and presenilin-1 mice(an Alzheimer’s disease model) and patients with Alzheimer’s disease.To investigate whether HTR3A-positive interneurons are associated with the production of Aβ plaques,we performed double immunostaining and found that HTR3A-positive interneurons were clustered around Aβ plaques in the mouse model.Some amyloid precursor protein-positive or β-site amyloid precursor protein cleaving enzyme-1-positive neurites near Aβ plaques were co-localized with HTR3A interneurons.These results suggest that HTR3A-positive interneurons may partially contribute to the generation of Aβ peptides.We treated 5.0-5.5-month-old model mice with tro pisetron,a HTR3 antagonist,for 8 consecutive weeks.We found that the cognitive deficit of mice was partially reversed,Aβ plaques and neuroinflammation we re remarkably reduced,the expression of HTR3 was remarkably decreased and the calcineurin/nuclear factor of activated T-cell 4 signaling pathway was inhibited in treated model mice.These findings suggest that HTR3A interneurons partly contribute to generation of Aβ peptide at the initial stage of Alzheimer’s disease and inhibiting HTR3 partly reve rses the pathological changes of Alzheimer’s disease.
