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
One important application of independent component analysis （ICA） is in image processing. A two dimensional （2-D） composite ICA algorithm framework for 2-D image independent component analysis （2-D ICA） is propo...One important application of independent component analysis （ICA） is in image processing. A two dimensional （2-D） composite ICA algorithm framework for 2-D image independent component analysis （2-D ICA） is proposed. The 2-D nature of the algorithm provides it an advantage of circumventing the roundabout transforming procedures between two dimensional （2-D） image deta and one-dimensional （l-D） signal. Moreover the combination of the Newton （fixed-point algorithm） and natural gradient algorithms in this composite algorithm increases its efficiency and robustness. The convincing results of a successful example in functional magnetic resonance imaging （fMRI） show the potential application of composite 2-D ICA in the brain activity detection.展开更多
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.
基金Supported by the 973 Project (No.2003CB716106), NSFC (No.90208003, 30200059), TRAPOYT, Doctor Training Fund of MOE, PRC, Key Research Project of Science and Technology of MOE, Fok Ying Tong Education Foundation (No.91041)
文摘One important application of independent component analysis （ICA） is in image processing. A two dimensional （2-D） composite ICA algorithm framework for 2-D image independent component analysis （2-D ICA） is proposed. The 2-D nature of the algorithm provides it an advantage of circumventing the roundabout transforming procedures between two dimensional （2-D） image deta and one-dimensional （l-D） signal. Moreover the combination of the Newton （fixed-point algorithm） and natural gradient algorithms in this composite algorithm increases its efficiency and robustness. The convincing results of a successful example in functional magnetic resonance imaging （fMRI） show the potential application of composite 2-D ICA in the brain activity detection.
