Activation of Autophagy Ameliorates Age-Related Neurogenesis Decline and Neurodysfunction in Adult Mice

Abstract

Adult neurogenesis is the ongoing generation of functional new neurons from neural progenitor cells (NPCs) in the mammalian brain. However, this process declines with aging, which is implicated in the recession of brain function and neurodegeneration. Understanding the mechanism of adult neurogenesis and stimulating it will bene t the mitigation of neurodegenerative diseases. Autophagy, a highly conserved process of cellular degradation, is essential for maintaining cellular homeostasis and normal function. Whether and how autophagy affects adult neurogenesis remains poorly understood. In present study, we revealed a close connection between impaired autophagy and adult neurogenetic decline. Expression of autophagy-related genes and autophagic activity were signi cantly declined in the middleaged subventricular/subgranular zone (SVZ/SGZ) homogenates and cultured NPCs, and inhibiting autophagy by siRNA interference resulted in impaired pluripotency of NPCs. Conversely, stimulating autophagy by rapamycin not only revitalized the viability and pluripotency of middle-aged NPCs, but also facilitated the neurogenesis in middle-aged SVZ/SGZ. More importantly, autophagic activation by rapamycin also ameliorated the olfactory sensitivity and cognitional capacities in middle-aged mice.Taken together, our results reveal that compromised autophagy is involved in the decline of adult neurogenesis, which could be reversed by autophagy activation. It also shed light on the regulation of adult neurogenesis and paves the way for developing therapeutic strategy for aging and neurodegenerative diseases.

The Impact of Hormesis, Neuronal Stress Response, and Reproduction, upon Clinical Aging: A Narrative Review

“…This must be because it has important actions to perform there [ 119 ]. It has positive actions on neuronal mitochondria [ 118 ], improves autophagy in neurons [ 120 ], and in germline stem cells [ 121 ], protects against synaptic degeneration [ 122 ] and exhibits general neuroprotective actions [ 123 ]. There are studies linking consumption of spermidine with a reduced risk of cognitive impairment in humans [ 124 ].…”

Fe3O4 Nanozymes Improve Neuroblast Differentiation and Blood-Brain Barrier Integrity of the Hippocampal Dentate Gyrus in D-Galactose-Induced Aged Mice

“…Ascorbic acid ameliorates D-gal induced injury and increases hippocampal neurogenesis through anti-oxidative effects [ 77 ]. Autophagy plays a key role in adult neurogenesis [ 78 ]. Autophagy promotes the proliferation and differentiation of neural stem cells by regulating reactive oxygen species and reducing intracellular oxidative stress [ 79 ].…”

The Multiple Roles of Autophagy in Neural Function and Diseases

“…Conversely, the knockdown of autophagy-associated genes led to impaired NPC proliferation and differentiation. Thus, impaired autophagy is related to a decline in adult neurogenesis, while activation of autophagy can reverse this phenotype [ 87 ].…”