Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease.Adult hippocampal neurogenesis is reduced in patients with Alzheimer’s disease.Exercise stimulates adult hippocampal neurogenesis in rode...Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease.Adult hippocampal neurogenesis is reduced in patients with Alzheimer’s disease.Exercise stimulates adult hippocampal neurogenesis in rodents and improves memory and slows cognitive decline in patients with Alzheimer’s disease.However,the molecular pathways for exercise-induced adult hippocampal neurogenesis and improved cognition in Alzheimer’s disease are poorly understood.Recently,regulator of G protein signaling 6(RGS6)was identified as the mediator of voluntary running-induced adult hippocampal neurogenesis in mice.Here,we generated novel RGS6fl/fl;APP_(SWE) mice and used retroviral approaches to examine the impact of RGS6 deletion from dentate gyrus neuronal progenitor cells on voluntary running-induced adult hippocampal neurogenesis and cognition in an amyloid-based Alzheimer’s disease mouse model.We found that voluntary running in APP_(SWE) mice restored their hippocampal cognitive impairments to that of control mice.This cognitive rescue was abolished by RGS6 deletion in dentate gyrus neuronal progenitor cells,which also abolished running-mediated increases in adult hippocampal neurogenesis.Adult hippocampal neurogenesis was reduced in sedentary APP_(SWE) mice versus control mice,with basal adult hippocampal neurogenesis reduced by RGS6 deletion in dentate gyrus neural precursor cells.RGS6 was expressed in neurons within the dentate gyrus of patients with Alzheimer’s disease with significant loss of these RGS6-expressing neurons.Thus,RGS6 mediated voluntary running-induced rescue of impaired cognition and adult hippocampal neurogenesis in APP_(SWE) mice,identifying RGS6 in dentate gyrus neural precursor cells as a possible therapeutic target in Alzheimer’s disease.展开更多
Background Mastitis is an inflammatory disease of the mammary gland that has serious economic impacts on the dairy industry and endangers food safety.Our previous study found that the body has a gut/rumen-mammary glan...Background Mastitis is an inflammatory disease of the mammary gland that has serious economic impacts on the dairy industry and endangers food safety.Our previous study found that the body has a gut/rumen-mammary gland axis and that disturbance of the gut/rumen microbiota could result in‘gastroenterogenic mastitis'.However,the mechanism has not been fully clarified.Recently,we found that long-term feeding of a high-concentrate diet induced mastitis in dairy cows,and the abundance of Stenotrophomonas maltophilia(S.maltophilia)was significantly increased in both the rumen and milk microbiota.Accordingly,we hypothesized that‘gastroenterogenic mastitis'can be induced by the migration of endogenous gut bacteria to the mammary gland.Therefore,this study investigated the mechanism by which enterogenic S.maltophilia induces mastitis.Results First,S.maltophilia was labelled with superfolder GFP and administered to mice via gavage.The results showed that treatment with S.maltophilia promoted the occurrence of mastitis and increased the permeability of the blood-milk barrier,leading to intestinal inflammation and intestinal leakage.Furthermore,tracking of ingested S.maltophilia revealed that S.maltophilia could migrate from the gut to the mammary gland and induce mastitis.Subsequently,mammary gland transcriptome analysis showed that the calcium and AMPK signalling pathways were significantly upregulated in mice treated with S.maltophilia.Then,using mouse mammary epithelial cells(MMECs),we verified that S.maltophilia induces mastitis through activation of the calcium-ROS-AMPK-mTOR-autophagy pathway.Conclusions In conclusion,the results showed that enterogenic S.maltophilia could migrate from the gut to the mammary gland via the gut-mammary axis and activate the calcium-ROS-AMPK-mTOR-autophagy pathway to induce mastitis.Targeting the gut-mammary gland axis may also be an effective method to treat mastitis.展开更多
基金supported by the National Institutes of Health,Nos.AA025919,AA025919-03S1,and AA025919-05S1(all to RAF).
文摘Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease.Adult hippocampal neurogenesis is reduced in patients with Alzheimer’s disease.Exercise stimulates adult hippocampal neurogenesis in rodents and improves memory and slows cognitive decline in patients with Alzheimer’s disease.However,the molecular pathways for exercise-induced adult hippocampal neurogenesis and improved cognition in Alzheimer’s disease are poorly understood.Recently,regulator of G protein signaling 6(RGS6)was identified as the mediator of voluntary running-induced adult hippocampal neurogenesis in mice.Here,we generated novel RGS6fl/fl;APP_(SWE) mice and used retroviral approaches to examine the impact of RGS6 deletion from dentate gyrus neuronal progenitor cells on voluntary running-induced adult hippocampal neurogenesis and cognition in an amyloid-based Alzheimer’s disease mouse model.We found that voluntary running in APP_(SWE) mice restored their hippocampal cognitive impairments to that of control mice.This cognitive rescue was abolished by RGS6 deletion in dentate gyrus neuronal progenitor cells,which also abolished running-mediated increases in adult hippocampal neurogenesis.Adult hippocampal neurogenesis was reduced in sedentary APP_(SWE) mice versus control mice,with basal adult hippocampal neurogenesis reduced by RGS6 deletion in dentate gyrus neural precursor cells.RGS6 was expressed in neurons within the dentate gyrus of patients with Alzheimer’s disease with significant loss of these RGS6-expressing neurons.Thus,RGS6 mediated voluntary running-induced rescue of impaired cognition and adult hippocampal neurogenesis in APP_(SWE) mice,identifying RGS6 in dentate gyrus neural precursor cells as a possible therapeutic target in Alzheimer’s disease.
基金supported by the National Natural Science Foundation of China(32102738,32122087,and 31972749)Scientific research project of Education Department of Jilin Province(No.JJKH20251201KJ)。
文摘Background Mastitis is an inflammatory disease of the mammary gland that has serious economic impacts on the dairy industry and endangers food safety.Our previous study found that the body has a gut/rumen-mammary gland axis and that disturbance of the gut/rumen microbiota could result in‘gastroenterogenic mastitis'.However,the mechanism has not been fully clarified.Recently,we found that long-term feeding of a high-concentrate diet induced mastitis in dairy cows,and the abundance of Stenotrophomonas maltophilia(S.maltophilia)was significantly increased in both the rumen and milk microbiota.Accordingly,we hypothesized that‘gastroenterogenic mastitis'can be induced by the migration of endogenous gut bacteria to the mammary gland.Therefore,this study investigated the mechanism by which enterogenic S.maltophilia induces mastitis.Results First,S.maltophilia was labelled with superfolder GFP and administered to mice via gavage.The results showed that treatment with S.maltophilia promoted the occurrence of mastitis and increased the permeability of the blood-milk barrier,leading to intestinal inflammation and intestinal leakage.Furthermore,tracking of ingested S.maltophilia revealed that S.maltophilia could migrate from the gut to the mammary gland and induce mastitis.Subsequently,mammary gland transcriptome analysis showed that the calcium and AMPK signalling pathways were significantly upregulated in mice treated with S.maltophilia.Then,using mouse mammary epithelial cells(MMECs),we verified that S.maltophilia induces mastitis through activation of the calcium-ROS-AMPK-mTOR-autophagy pathway.Conclusions In conclusion,the results showed that enterogenic S.maltophilia could migrate from the gut to the mammary gland via the gut-mammary axis and activate the calcium-ROS-AMPK-mTOR-autophagy pathway to induce mastitis.Targeting the gut-mammary gland axis may also be an effective method to treat mastitis.
