Klotho regulates postnatal neurogenesis and protects against age-related spatial memory loss

Ann M. Laszczyk, Stephanie Fox-Quick, Hai T. Vo, Dailey Nettles, Phyllis C. Pugh, Linda Overstreet-Wadiche, Gwendalyn D. King

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Although the absence of the age-regulating klotho protein causes klotho-deficient mice to rapidly develop cognitive impairment and increasing klotho enhances hippocampal-dependent memory, the cellular effects of klotho that mediate hippocampal-dependent memory function are unknown. Here, we show premature aging of the klotho-deficient hippocampal neurogenic niche as evidenced by reduced numbers of neural stem cells, decreased proliferation, and impaired maturation of immature neurons. Klotho-deficient neurospheres show reduced proliferation and size that is rescued by supplementation with shed klotho protein. Conversely, 6-month-old klotho-overexpressing mice exhibit increased numbers of neural stem cells, increased proliferation, and more immature neurons with enhanced dendritic arborization. Protection from normal age-related loss of object location memory with klotho overexpression and loss of spatial memory when klotho is reduced by even half suggests direct, local effects of the protein. Together, these data show that klotho is a novel regulator of postnatal neurogenesis affecting neural stem cell proliferation and maturation sufficient to impact hippocampal-dependent spatial memory function.

Original languageEnglish (US)
Pages (from-to)41-54
Number of pages14
JournalNeurobiology of Aging
Volume59
DOIs
StatePublished - Nov 2017
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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