Dataset Information

Peripheral Elevation of a Klotho Fragment Enhances Brain Function and Resilience in Young, Aging, and ?-Synuclein Transgenic Mice.

ABSTRACT: Cognitive dysfunction and decreased mobility from aging and neurodegenerative conditions, such as Parkinson and Alzheimer diseases, are major biomedical challenges in need of more effective therapies. Increasing brain resilience may represent a new treatment strategy. Klotho, a longevity factor, enhances cognition when genetically and broadly overexpressed in its full, wild-type form over the mouse lifespan. Whether acute klotho treatment can rapidly enhance cognitive and motor functions or induce resilience is a gap in our knowledge of its therapeutic potential. Here, we show that an ?-klotho protein fragment (?KL-F), administered peripherally, surprisingly induced cognitive enhancement and neural resilience despite impermeability to the blood-brain barrier in young, aging, and transgenic ?-synuclein mice. ?KL-F treatment induced cleavage of the NMDAR subunit GluN2B and also enhanced NMDAR-dependent synaptic plasticity. GluN2B blockade abolished ?KL-F-mediated effects. Peripheral ?KL-F treatment is sufficient to induce neural enhancement and resilience in mice and may prove therapeutic in humans.

SUBMITTER: Leon J

PROVIDER: S-EPMC5816951 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Peripheral Elevation of a Klotho Fragment Enhances Brain Function and Resilience in Young, Aging, and α-Synuclein Transgenic Mice.

Leon Julio J Moreno Arturo J AJ Garay Bayardo I BI Chalkley Robert J RJ Burlingame Alma L AL Wang Dan D Dubal Dena B DB

Cell reports 20170801 6

Cognitive dysfunction and decreased mobility from aging and neurodegenerative conditions, such as Parkinson and Alzheimer diseases, are major biomedical challenges in need of more effective therapies. Increasing brain resilience may represent a new treatment strategy. Klotho, a longevity factor, enhances cognition when genetically and broadly overexpressed in its full, wild-type form over the mouse lifespan. Whether acute klotho treatment can rapidly enhance cognitive and motor functions or indu ...[more]

PMID: 28793260

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Project description:Desiccation tolerance is a complex phenomenon that depends on the regulated expression of numerous genes during dehydration and subsequent rehydration. Our previous study identified a chloroplast drought-induced stress protein (MaCDSP32) in mulberry, a thioredoxin (Trx) that is upregulated under drought conditions and is likely to confer drought tolerance to transgenic plants. Mulberry (Morus spp.) is an ecologically and economically important perennial woody plant that is widely used in forest management to combat desertification. However, its stress tolerance physiology is not well understood. In this study, the functions of MaCDSP32 gene were investigated. The expression of MaCDSP32 exhibited a circadian rhythm and was induced by mild and severe water deficits. Under abiotic stress, MaCDSP32-overexpressing plants exhibited increased stress sensitivity with lower water retention capacity and more severe lipid peroxidation than the wild-type (WT) plants. Furthermore, the activity of superoxide dismutase (SOD), the contents of proline and soluble sugars and the expression of stress-related transcription factors were lower in the MaCDSP32-overexpressing plants than in the WT plants. However, the MaCDSP32-overexpressing lines exhibited stronger recovery capability after rewatering post-drought. Moreover, the SOD enzyme activity, proline content, and soluble sugar content were higher in the transgenic plants after rewatering than in the WT plants. The production of the reactive oxygen species (ROS) H2O2 and O2 - was significantly lower in the transgenic plants than in the WT plants. In addition, under abiotic stress, the MaCDSP32-overexpressing lines exhibited improved seed germination and seedling growth, these effects were regulated by a positive redox reaction involving MaCDSP32 and one of its targets. In summary, this study indicated that MaCDSP32 from mulberry regulates plant drought tolerance and ROS homeostasis mainly by controlling SOD enzyme activity and proline and soluble sugar concentrations and that this control might trigger the stress response during seed germination and plant growth. Overall, MaCDSP32 exerts pleiotropic effects on the stress response and stress recovery in plants.

Dataset Information

Peripheral Elevation of a Klotho Fragment Enhances Brain Function and Resilience in Young, Aging, and ?-Synuclein Transgenic Mice.

Publications

Peripheral Elevation of a Klotho Fragment Enhances Brain Function and Resilience in Young, Aging, and α-Synuclein Transgenic Mice.

Similar Datasets

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