A role for Lin28a in aging-associated decline of adult hippocampal neurogenesis

Abstract

Hippocampal neurogenesis declines with aging. Wnt ligands and antagonists within the hippocampal neurogenic niche regulate the proliferation of neural progenitor cells and the development of new neurons, and the changes of their levels in the niche mediate aging-associated decline of neurogenesis. We found that RNA-binding protein Lin28a remained existent in neural progenitor cells and granule neurons in the adult hippocampus, and decreased with aging. Loss of Lin28a inhibited the responsiveness of neural progenitor cells to niche Wnt agonist and reduced neurogenesis, thus impairing pattern separation. Overexpression of Lin28a increased the proliferation of neural progenitor cells, promoted the functional integration of newborn neurons, restored neurogenesis in Wnt-deficient dentate gyrus, and rescued the impaired pattern separation in aging mice. Our data suggest that Lin28a regulates adult hippocampal neurogenesis as an intracellular mechanism by responding to niche Wnt signals, and its decrease is involved in aging-associated decline of hippocampal neurogenesis as well as related cognitive functions.

LIN28 Family in Testis: Control of Cell Renewal, Maturation, Fertility and Aging

“…However, its expression declines and is significantly downregulated with the developmental progression in most differentiated adult tissues [10], with some exceptions. LIN28 was found in neural progenitor cells of the mouse brain and was overexpressed in the neurons of the adult hippocampus, supporting neurogenesis, while it decreased during aging [11]. Such features seem to be tissue-dependent, as high LIN28A expression has recently been found in neonatal cardiac-tissue-derived stem-like cells (CTSCs) during heart development, but, in adult CTSCs, expression was low or absent [12].…”

“…[33] tail development mouse [39] tooth development mouse [40] trophoblast proliferation human 1 and sheep neurogliogenesis Rat and mouse [41] ovulation C. elegans [42] trophoblast differentiation human [15] mesodermal and neural cell fate mouse [39] hippocampal neurogenesis mouse [11] germline stem cells self-renewal human [22] 1 [23] 1 body height human [28][29][30] LIN28B paralog finger length ratio human [31] adiposity human [32] placenta development human [43,44] hematopoietic maturation mouse [13];…”