β2-Microglobulin(β2M),a component of the major histocompatibility complex class I molecule,is associated with aging-related cognitive impairment and Alzheimer’s disease.Although upregulation ofβ2M is considered to...β2-Microglobulin(β2M),a component of the major histocompatibility complex class I molecule,is associated with aging-related cognitive impairment and Alzheimer’s disease.Although upregulation ofβ2M is considered to be highly related to ischemic stroke,the specific role and underlying mechanistic action ofβ2M are poorly understood.In this study,we established a rat model of focal cerebral ischemia by occlusion of the middle cerebral artery.We found thatβ2M levels in the cerebral spinal fluid,serum,and brain tissue were significantly increased in the acute period but gradually decreased during the recovery period.RNA interference was used to inhibitβ2M expression in the acute period of cerebral stroke.Tissue staining with 2,3,5-triphenyltetrazolium chloride and evaluation of cognitive function using the Morris water maze test demonstrated that decreasedβ2M expression in the ischemic penumbra reduced infarct volume and alleviated cognitive deficits,respectively.Notably,glial cell,caspase-1(p20),and Nod-like receptor pyrin domain containing 3(NLRP3)inflammasome activation as well as production of the inflammatory cytokines interleukin-1β,interleukin-6,and tumor necrosis factor-αwere also effectively inhibited byβ2M silencing.These findings suggest thatβ2M participates in brain injury and cognitive impairment in a rat model of ischemic stroke through activation of neuroinflammation associated with the NLRP3 inflammasome.展开更多
Studies have shown that mesenchymal stem cell-derived exosomes can enhance neural plasticity and improve cognitive impairment.The purpose of this study was to investigate the effects of mesenchymal stem cell-derived e...Studies have shown that mesenchymal stem cell-derived exosomes can enhance neural plasticity and improve cognitive impairment.The purpose of this study was to investigate the effects of mesenchymal stem cell-derived exosomes on neurogenesis and cognitive capacity in a mouse model of Alzheimer’s disease.Alzheimer’s disease mouse models were established by injection of beta amyloid 1?42 aggregates into dentate gyrus bilaterally.Morris water maze and novel object recognition tests were performed to evaluate mouse cognitive deficits at 14 and 28 days after administration.Afterwards,neurogenesis in the subventricular zone was determined by immunofluorescence using doublecortin and PSA-NCAM antibodies.Results showed that mesenchymal stem cells-derived exosomes stimulated neurogenesis in the subventricular zone and alleviated beta amyloid 1?42-induced cognitive impairment,and these effects are similar to those shown in the mesenchymal stem cells.These findings provide evidence to validate the possibility of developing cell-free therapeutic strategies for Alzheimer’s disease.All procedures and experiments were approved by Institutional Animal Care and Use Committee(CICUAL)(approval No.CICUAL 2016-011)on April 25,2016.展开更多
Present study was aimed to evaluate the effect HiOwna-Jr. (FFD-410) on vital biochemical, hematological, immunological and cognitive functions in rats;also in vitro antioxidant studies were carried out to evaluate the...Present study was aimed to evaluate the effect HiOwna-Jr. (FFD-410) on vital biochemical, hematological, immunological and cognitive functions in rats;also in vitro antioxidant studies were carried out to evaluate the antioxidant capacity of FFD-410. Animals of respective groups were treatment with FFD-410 for 90 days and blood samples were collected for the estimation of biochemical, hematological parameters and serum immunoglobulin levels;haemoagglutination assay was carried out using Sheep Red blood cells (SRBC’s). In addition, effect of FFD-410 on cognition and memory was evaluated by modified elevated plus maze test. Apart from in vivo studies, in vitro studies such as DPPH radical scavenging assay, reducing power assay and ORAC assays were carried out to evaluate the free radical scavenging and antioxidant activity of FFD-410. Pretreatment with FFD-410 for 90 days did not bring about any change in serum biochemical and hematological parameters and relative organ weights etc., which could account for its wide safety margin at tested dose levels (2.5 and 5.0 g/kg, p.o.). However, FFD-410 showed potent immunostimulant activity by elevating the serum immunoglobulins and haemoagglutination titer values, also the pretreatment with FFD-410 showed dose dependent improvement in short-term cognition and memory in elevated plus maze test. Furthermore, in vitro antioxidant studies FFD-410 exhibited significant and dose dependent free radical scavenging and antioxidant activity as assessed by DPPH (IC50 value of 1162.6 μg/ml), reducing power and ORAC assays (Trolox equivalence/g of 76.1). These findings suggest that, FFD-410 possess very good antioxidant, cognition improving and potent immunostimulant properties. Also, there was no significant change in the serum biochemical and hematological parameters and relative organ weights were observed after 90 days treatment with FFD-410, which could account for its wide safety of margin at tested dose levels (2.5 and5.0 g/kg. p.o.).展开更多
基金supported by the National Natural Science Foundation of China,No.81771337(to RQY).
文摘β2-Microglobulin(β2M),a component of the major histocompatibility complex class I molecule,is associated with aging-related cognitive impairment and Alzheimer’s disease.Although upregulation ofβ2M is considered to be highly related to ischemic stroke,the specific role and underlying mechanistic action ofβ2M are poorly understood.In this study,we established a rat model of focal cerebral ischemia by occlusion of the middle cerebral artery.We found thatβ2M levels in the cerebral spinal fluid,serum,and brain tissue were significantly increased in the acute period but gradually decreased during the recovery period.RNA interference was used to inhibitβ2M expression in the acute period of cerebral stroke.Tissue staining with 2,3,5-triphenyltetrazolium chloride and evaluation of cognitive function using the Morris water maze test demonstrated that decreasedβ2M expression in the ischemic penumbra reduced infarct volume and alleviated cognitive deficits,respectively.Notably,glial cell,caspase-1(p20),and Nod-like receptor pyrin domain containing 3(NLRP3)inflammasome activation as well as production of the inflammatory cytokines interleukin-1β,interleukin-6,and tumor necrosis factor-αwere also effectively inhibited byβ2M silencing.These findings suggest thatβ2M participates in brain injury and cognitive impairment in a rat model of ischemic stroke through activation of neuroinflammation associated with the NLRP3 inflammasome.
基金sponsored by CONACYT scholarship#487713Fondo Mixto de Ciencia y Tecnología del Estado de Jalisco grant JAL-2014-0-250508
文摘Studies have shown that mesenchymal stem cell-derived exosomes can enhance neural plasticity and improve cognitive impairment.The purpose of this study was to investigate the effects of mesenchymal stem cell-derived exosomes on neurogenesis and cognitive capacity in a mouse model of Alzheimer’s disease.Alzheimer’s disease mouse models were established by injection of beta amyloid 1?42 aggregates into dentate gyrus bilaterally.Morris water maze and novel object recognition tests were performed to evaluate mouse cognitive deficits at 14 and 28 days after administration.Afterwards,neurogenesis in the subventricular zone was determined by immunofluorescence using doublecortin and PSA-NCAM antibodies.Results showed that mesenchymal stem cells-derived exosomes stimulated neurogenesis in the subventricular zone and alleviated beta amyloid 1?42-induced cognitive impairment,and these effects are similar to those shown in the mesenchymal stem cells.These findings provide evidence to validate the possibility of developing cell-free therapeutic strategies for Alzheimer’s disease.All procedures and experiments were approved by Institutional Animal Care and Use Committee(CICUAL)(approval No.CICUAL 2016-011)on April 25,2016.
文摘Present study was aimed to evaluate the effect HiOwna-Jr. (FFD-410) on vital biochemical, hematological, immunological and cognitive functions in rats;also in vitro antioxidant studies were carried out to evaluate the antioxidant capacity of FFD-410. Animals of respective groups were treatment with FFD-410 for 90 days and blood samples were collected for the estimation of biochemical, hematological parameters and serum immunoglobulin levels;haemoagglutination assay was carried out using Sheep Red blood cells (SRBC’s). In addition, effect of FFD-410 on cognition and memory was evaluated by modified elevated plus maze test. Apart from in vivo studies, in vitro studies such as DPPH radical scavenging assay, reducing power assay and ORAC assays were carried out to evaluate the free radical scavenging and antioxidant activity of FFD-410. Pretreatment with FFD-410 for 90 days did not bring about any change in serum biochemical and hematological parameters and relative organ weights etc., which could account for its wide safety margin at tested dose levels (2.5 and 5.0 g/kg, p.o.). However, FFD-410 showed potent immunostimulant activity by elevating the serum immunoglobulins and haemoagglutination titer values, also the pretreatment with FFD-410 showed dose dependent improvement in short-term cognition and memory in elevated plus maze test. Furthermore, in vitro antioxidant studies FFD-410 exhibited significant and dose dependent free radical scavenging and antioxidant activity as assessed by DPPH (IC50 value of 1162.6 μg/ml), reducing power and ORAC assays (Trolox equivalence/g of 76.1). These findings suggest that, FFD-410 possess very good antioxidant, cognition improving and potent immunostimulant properties. Also, there was no significant change in the serum biochemical and hematological parameters and relative organ weights were observed after 90 days treatment with FFD-410, which could account for its wide safety of margin at tested dose levels (2.5 and5.0 g/kg. p.o.).
