Dataset Information

The Protective Effects of Osteocyte-Derived Extracellular Vesicles Against Alzheimer's Disease Diminished with Aging.

ABSTRACT: Both Alzheimer's disease (AD) and osteoporosis (OP) are common age-associated degenerative diseases and are strongly correlated with clinical epidemiology. However, there is a lack of clear pathological relationship between the brain and bone in the current understanding. Here, it is found that young osteocyte, the most abundant cells in bone, secretes extracellular vesicles (OCY^Young -EVs) to ameliorate cognitive impairment and the pathogenesis of AD in APP/PS1 mice and model cells. These benefits of OCY^Young -EVs are diminished in aged osteocyte-derived EVs (OCY^Aged -EVs). Based on the self-constructed OCY-EVs tracer transgenic mouse models and the in vivo fluorescent imaging system, OCY-EVs have been observed to be transported to the brain under physiological and pathological conditions. In the hippocampal administration of Aβ40 induced young AD model mice, the intramedullary injection of Rab27a-shRNA adenovirus inhibits OCY^Young -EVs secretion from bone and aggravates cognitive impairment. Proteomic quantitative analysis reveals that OCY^Young -EVs, compared to OCY^Aged -EVs, enrich multiple protective factors of AD pathway. The study uncovers the role of OCY-EV as a regulator of brain health, suggesting a novel mechanism in bone-brain communication.

SUBMITTER: Jiang YL

PROVIDER: S-EPMC9189667 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Protective Effects of Osteocyte-Derived Extracellular Vesicles Against Alzheimer's Disease Diminished with Aging.

Jiang Ya-Ling YL Wang Zhen-Xing ZX Liu Xi-Xi XX Wan Mei-Dan MD Liu Yi-Wei YW Jiao Bin B Liao Xin-Xin XX Luo Zhong-Wei ZW Wang Yi-Yi YY Hong Chun-Gu CG Tan Yi-Juan YJ Weng Ling L Zhou Ya-Fang YF Rao Shan-Shan SS Cao Jia J Liu Zheng-Zhao ZZ Wan Teng-Fei TF Zhu Yuan Y Xie Hui H Shen Lu L

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20220504 17

Both Alzheimer's disease (AD) and osteoporosis (OP) are common age-associated degenerative diseases and are strongly correlated with clinical epidemiology. However, there is a lack of clear pathological relationship between the brain and bone in the current understanding. Here, it is found that young osteocyte, the most abundant cells in bone, secretes extracellular vesicles (OCY<sup>Young</sup> -EVs) to ameliorate cognitive impairment and the pathogenesis of AD in APP/PS1 mice and model cells. ...[more]

PMID: 35508803

Similar Datasets

Project description:Extracellular vesicles (EVs) are lipid bilayered compartments released by virtually all living cells, including fungi. Among the diverse molecules carried by fungal EVs, a number of immunogens, virulence factors and regulators have been characterised. Within EVs, these components could potentially impact disease outcomes by interacting with the host. From this perspective, we previously demonstrated that EVs from Candida albicans could be taken up by and activate macrophages and dendritic cells to produce cytokines and express costimulatory molecules. Moreover, pre-treatment of Galleria mellonella larvae with fungal EVs protected the insects against a subsequent lethal infection with C. albicans yeasts. These data indicate that C. albicans EVs are multi-antigenic compartments that activate the innate immune system and could be exploited as vaccine formulations. Here, we investigated whether immunisation with C. albicans EVs induces a protective effect against murine candidiasis in immunosuppressed mice. Total and fungal antigen-specific serum IgG antibodies increased by 21 days after immunisation, confirming the efficacy of the protocol. Vaccination decreased fungal burden in the liver, spleen and kidney of mice challenged with C. albicans. Splenic levels of cytokines indicated a lower inflammatory response in mice immunised with EVs when compared with EVs + Freund's adjuvant (ADJ). Higher levels of IL-12p70, TNFα and IFNγ were detected in mice vaccinated with EVs + ADJ, while IL-12p70, TGFβ, IL-4 and IL-10 were increased when no adjuvants were added. Full protection of lethally challenged mice was observed when EVs were administered, regardless the presence of adjuvant. Physical properties of the EVs were also investigated and EVs produced by C. albicans were relatively stable after storage at 4, -20 or -80°C, keeping their ability to activate dendritic cells and to protect G. mellonella against a lethal candidiasis. Our data suggest that fungal EVs could be a safe source of antigens to be exploited in vaccine formulations.

Dataset Information

The Protective Effects of Osteocyte-Derived Extracellular Vesicles Against Alzheimer's Disease Diminished with Aging.

Publications

The Protective Effects of Osteocyte-Derived Extracellular Vesicles Against Alzheimer's Disease Diminished with Aging.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets