Optogenetics is a combination of optics and genetics technology that can be used to activate or inhibit specific cells in tissues. It has been used to treat Parkinson’s disease, epilepsy and neurological diseases, bu...Optogenetics is a combination of optics and genetics technology that can be used to activate or inhibit specific cells in tissues. It has been used to treat Parkinson’s disease, epilepsy and neurological diseases, but rarely Alzheimer’s disease. Adeno-associated virus carrying the CaMK promoter driving the optogenetic channelrhodopsin-2 (CHR2) gene (or without the CHR2 gene, as control) was injected into the bilateral dentate gyri, followed by repeated intrahippocampal injections of soluble low-molecular-weight amyloid-β1–42 peptide (Aβ1–42). Subsequently, the region was stimulated with a 473 nm laser (1–3 ms, 10 Hz, 5 minutes). The novel object recognition test was conducted to test memory function in mice. Immunohistochemical staining was performed to analyze the numbers of NeuN and synapsin Ia/b-positive cells in the hippocampus. Western blot assay was carried out to analyze the expression levels of glial fibrillary acidic protein, NeuN, synapsin Ia/b, metabotropic glutamate receptor-1a (mGluR-1a), mGluR-5, N-methyl-D-aspartate receptor subunit NR1, glutamate receptor 2, interleukin-1β, interleukin-6 and interleukin-10. Optogenetic stimulation improved working and short-term memory in mice with Alzheimer’s disease. This neuroprotective effect was associated with increased expression of NR1, glutamate receptor 2 and mGluR-5 in the hippocampus, and decreased expression of glial fibrillary acidic protein and interleukin-6. Our results show that optogenetics can be used to regulate the neuronal-glial network to ameliorate memory functions in mice with Alzheimer’s disease. The study was approved by the Animal Resources Committee of Jinan University, China (approval No. LL-KT-2011134) on February 28, 2011.展开更多
Two novel 18-crown-6-ether(18-C-6)directed one-dimensional silver(I)coordination polymers(1D Ag(I)CPs),formulated as{[(18-C-6)Ag(bpy)]⋅X}_(∞)and{[(18-C-6)Ag(pyz)]⋅X}_(∞){bpy=4,4′-bipyridine;pyz=pyrazine;X=BF_(4)^(...Two novel 18-crown-6-ether(18-C-6)directed one-dimensional silver(I)coordination polymers(1D Ag(I)CPs),formulated as{[(18-C-6)Ag(bpy)]⋅X}_(∞)and{[(18-C-6)Ag(pyz)]⋅X}_(∞){bpy=4,4′-bipyridine;pyz=pyrazine;X=BF_(4)^(-)(Ⅰa,Ⅱa),CF_(3)SO_(3)^(-)(Ⅰb,Ⅱb)},are prepared and structurally determined.The protection of the 18-C-6 macrocycle not only efficiently prevents intermolecular interactions within each 1D Ag(I)CP but also significantly enhances the rigidity of the chain structures,allowing these polymers to exhibit remarkable phosphorescence with intense green-light emission at room temperature.Moreover,Ⅱa and Ⅱb show enhanced photoluminescence quantum yields and aggregation-induced emission properties,which can be attributed to their close-packed structure modes in the crystalline states.Interestingly,upon mixing with commercial resin,Ⅱa can serve as an efficient and stable luminescent ink for 3D printing.The resulting printed structures demonstrate exceptional irradiation stability,retaining their luminescence properties without any quenching over a three-month period.This work not only provides a facile strategy to prepare luminescent 1D Ag(I)CPs but also shows the promise of their utilization in optical devices.展开更多
基金supported by the National Natural Science Foundation of China,No.81171191(to LYZ)the Shenzhen Special Fund Project on Strategic Emerging Industry Development of China,No.JCYJ20160422170522075(to LYZ)the Shenzhen Healthcare Research Project of China,No.201601015(to LYZ)
文摘Optogenetics is a combination of optics and genetics technology that can be used to activate or inhibit specific cells in tissues. It has been used to treat Parkinson’s disease, epilepsy and neurological diseases, but rarely Alzheimer’s disease. Adeno-associated virus carrying the CaMK promoter driving the optogenetic channelrhodopsin-2 (CHR2) gene (or without the CHR2 gene, as control) was injected into the bilateral dentate gyri, followed by repeated intrahippocampal injections of soluble low-molecular-weight amyloid-β1–42 peptide (Aβ1–42). Subsequently, the region was stimulated with a 473 nm laser (1–3 ms, 10 Hz, 5 minutes). The novel object recognition test was conducted to test memory function in mice. Immunohistochemical staining was performed to analyze the numbers of NeuN and synapsin Ia/b-positive cells in the hippocampus. Western blot assay was carried out to analyze the expression levels of glial fibrillary acidic protein, NeuN, synapsin Ia/b, metabotropic glutamate receptor-1a (mGluR-1a), mGluR-5, N-methyl-D-aspartate receptor subunit NR1, glutamate receptor 2, interleukin-1β, interleukin-6 and interleukin-10. Optogenetic stimulation improved working and short-term memory in mice with Alzheimer’s disease. This neuroprotective effect was associated with increased expression of NR1, glutamate receptor 2 and mGluR-5 in the hippocampus, and decreased expression of glial fibrillary acidic protein and interleukin-6. Our results show that optogenetics can be used to regulate the neuronal-glial network to ameliorate memory functions in mice with Alzheimer’s disease. The study was approved by the Animal Resources Committee of Jinan University, China (approval No. LL-KT-2011134) on February 28, 2011.
基金K.-G.Liu is grateful for financial support from the National Natural Science Foundation of China(Grant No.92161106)the Natural Science Foundation of Ningxia(Grant No.2023AA02004)+2 种基金J.Wei is grateful for financial support from the Natural Science Foundation of Ningxia(Grant No.2024AAC03032)X.Yang is grateful for financial support from the Key Research and Development Program of Ningxia(Grant No.2021BEB04066)The authors acknowledge the French Grand Equipment National de Calcul Intensif for HCP support(Project a0010807367).
文摘Two novel 18-crown-6-ether(18-C-6)directed one-dimensional silver(I)coordination polymers(1D Ag(I)CPs),formulated as{[(18-C-6)Ag(bpy)]⋅X}_(∞)and{[(18-C-6)Ag(pyz)]⋅X}_(∞){bpy=4,4′-bipyridine;pyz=pyrazine;X=BF_(4)^(-)(Ⅰa,Ⅱa),CF_(3)SO_(3)^(-)(Ⅰb,Ⅱb)},are prepared and structurally determined.The protection of the 18-C-6 macrocycle not only efficiently prevents intermolecular interactions within each 1D Ag(I)CP but also significantly enhances the rigidity of the chain structures,allowing these polymers to exhibit remarkable phosphorescence with intense green-light emission at room temperature.Moreover,Ⅱa and Ⅱb show enhanced photoluminescence quantum yields and aggregation-induced emission properties,which can be attributed to their close-packed structure modes in the crystalline states.Interestingly,upon mixing with commercial resin,Ⅱa can serve as an efficient and stable luminescent ink for 3D printing.The resulting printed structures demonstrate exceptional irradiation stability,retaining their luminescence properties without any quenching over a three-month period.This work not only provides a facile strategy to prepare luminescent 1D Ag(I)CPs but also shows the promise of their utilization in optical devices.