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Mol Psychiatry. 2018 Sep;23(9):1-11. doi: 10.1038/mp.2017.211. Epub 2017 Oct 31.

Secreted αKlotho isoform protects against age-dependent memory deficits.

Author information

1
Department of Biochemistry and Molecular Biology, Universitat Autònoma Barcelona 5th level, Edifici H, Institut Neurociencies, Campus UAB, Bellaterra, Spain.
2
Institute de Neurociènces (INc), Universitat Autònoma Barcelona, Campus UAB, Bellaterra, Spain.
3
Centro de Investigación Biomédica en Red sobre enfermedades Neurodegenerativas (CIBERNED), Instituto Carlos III, Madrid, Spain.
4
Institute de Neurociènces (INc), Universitat Autònoma Barcelona, Campus UAB, Bellaterra, Spain. lidia.gimenez@uab.cat.
5
Department of Psychiatry and Forensic Medicine, School of Medicine, Universitat Autònoma de Barcelona, Campus UAB, Bellaterra, Spain. lidia.gimenez@uab.cat.
6
Department of Biochemistry and Molecular Biology, Universitat Autònoma Barcelona 5th level, Edifici H, Institut Neurociencies, Campus UAB, Bellaterra, Spain. miguel.chillon@uab.es.
7
Institute de Neurociènces (INc), Universitat Autònoma Barcelona, Campus UAB, Bellaterra, Spain. miguel.chillon@uab.es.
8
Vall d'Hebron Institut de Recerca (VHIR), Research Group on Gene Therapy at Nervous System, Passeig de la Vall d'Hebron, Barcelona, Spain. miguel.chillon@uab.es.
9
Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain. miguel.chillon@uab.es.

Abstract

αKlotho is a gene regulator of aging, increasing life expectancy when overexpressed and accelerating the development of aging phenotypes when inhibited. In mice, expression levels of the secreted isoform Klotho (s-KL) are very high in the brain, suggesting that s-KL activity may have an important role in the nervous system. Here we study the functional relevance at behavioural level of modifying s-KL levels in the aging brain. We used AAVrh10 vectors to deliver and sustained expression of s-KL in 6- and 12-month-old wild-type C57BL/6J males. This study demonstrates for we believe the first time in vivo that 6 months after a single injection of s-KL into the central nervous system, long-lasting and quantifiable enhancement of learning and memory capabilities are found. More importantly, cognitive improvement is also observable in 18-month-old mice treated once, at 12 months of age. These findings demonstrate the therapeutic potential of s-KL as a treatment for cognitive decline associated with aging.

PMID:
29086766
DOI:
10.1038/mp.2017.211

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