MicroRNA-153 improves the neurogenesis of neural stem cells and enhances the cognitive ability of aged mice through the notch signaling pathway

Abstract

Aging-related cognitive ability impairments are one of the main threats to public health, and impaired hippocampal neurogenesis is a major cause of cognitive decline during aging. However, the regulation of adult neurogenesis in the hippocampus requires further study. Here, we investigated the role of microRNA-153 (miR-153), a highly conserved microRNA in mice and humans, in adult neurogenesis. During the passaging of neural stem cells (NSCs) in vitro, endogenous miR-153 expression was downregulated, with a decrease in neuronal differentiation ability. In addition, miR-153 overexpression increased the neurogenesis of NSCs. Further studies showed that miR-153 regulated neurogenesis by precisely targeting the Notch signaling pathway through inhibition of Jagged1 and Hey2 translation. In vivo analysis demonstrated that miR-153 expression was decreased in the hippocampi of aged mice with impaired cognitive ability, and that miR-153 overexpression in the hippocampus promoted neurogenesis and markedly increased the cognitive abilities of the aged mice. Overall, our findings revealed that miR-153 affected neurogenesis by regulating the Notch signaling pathway and elucidated the function of miR-153 in aging-related, hippocampus-dependent cognitive ability impairments, and neurodegenerative diseases.

Responsiveness of dentate neurons generated throughout adult life is associated with resilience to cognitive aging

“…Here, we found that between middle age and senescence, the number of cells is further decreased, but then a difference between the AU and AI groups appears. Based on previous data, it is likely that the emergence of such a difference results from a difference in cell proliferation (Drapeau et al., 2003), neuronal differentiation (Drapeau et al., 2003; Qiao et al., 2019), cellular senescence (Hernandez‐Segura, Nehme, & Demaria, 2018; Micheli et al., 2019), or changes in the neurogenic niche and/or to the systemic milieu (Mahmoudi, Xu, & Brunet, 2019; Villeda et al., 2011). Interestingly, we have shown that the senescent neurogenic niche is capable to rejuvenate upon removal of corticosterone (Montaron et al., 1999) or addition of pregnenolone sulfate (Mayo et al., 2005), indicating that neural stem cells are not depleted and keep their abilities to divide.…”

Resilience to cognitive aging is associated with responsiveness of dentate neurons generated throughout adult life

“…Here, we found that between middle-age and senescence the number of cells is further decreased, but then a difference among the AU and AI groups appears. Based on previous data, it is likely that the emergence of such a difference results from a difference in cell proliferation (Diaz-Moreno et al, 2018;Drapeau et al, 2003), neuronal differentiation (Drapeau et al, 2003;Qiao et al, 2019), cellular senescence (Hernandez-Segura et al, 2018;Micheli et al, 2019), changes in the neurogenic niche (Fan et al, 2017) and/or to the systemic milieu (Mahmoudi et al, 2019;Smith et al, 2015;Villeda et al, 2011). Interestingly, we have shown that the senescent neurogenic niche is capable to rejuvenate upon removal of corticosterone (Montaron et al, 1999) or addition of Sulfate pregnenologne (Mayo et al, 2005) indicating that neural stem cells are not depleted and keep their abilities to divide.…”

Modulation of MicroRNAs as a Potential Molecular Mechanism Involved in the Beneficial Actions of Physical Exercise in Alzheimer Disease

“…Knockdown of endogenous miR-34a in murine neural progenitor cells and NSCs resulted in increased expression of Numbl, NeuroD1, and Mash1 along with decreased Notch1 expression [ 62 , 97 ]. A recent study in aged mice showed that miR-153 is downregulated in the hippocampus, and that miR-153 overexpression increased neurogenesis by interfering with the Notch signaling pathway [ 67 ].…”

“… Representative miRNAs involved in neural development and function. Let-7b [ 58 , 59 ], miR-9 [ 58 , 59 ], miR-17-92 cluster [ 60 ], miR-29a [ 61 ], miR-34a [ 62 ], miR-124 [ 58 ], miR-132 [ 63 ], miR-134 [ 64 ], miR-137 [ 65 ], miR-146 [ 66 ], miR-153 [ 67 ], miR-184 [ 58 ], miR-212 [ 68 ], miR-223 [ 69 ], miR-9 [ 70 ], miR-128 [ 71 ], miR-129 [ 72 ], miR-132 [ 70 ], miR-139 [ 73 ], miR-379-410 cluster [ 74 ], miR-9 [ 75 ], miR-101 [ 76 ], miR-132 [ 77 ], miR-214 [ 78 ], miR-21 [ 79 ], miR-30a [ 80 ], miR-34a [ 81 ], miR-124 [ 81 ], miR-125b [ 82 ], miR-146a [ 83 ], miR-155 [ 81 ], miR-200b [ 79 ], miR-223 [ 57 ], miR-298 [ 79 ], miR-362 [ 79 ], miR-9 [ 84 ], miR-29a/b [ 57 ], miR-124 [ 84 ], miR-125a/b [ 64 ], miR-132 [ 64 ], miR-134 [ 64 ], miR-138 [ 58 ], miR-181 [ 85 ], miR-182 [ 86 ], miR-219 [ 87 ], miR-223 [ 57 ], miR-284 [ 88 ], let-7 [ …”