摘要：SummaryAxonal repair is critical for functional recovery after injury of the CNS. We previously reported that neuronalPTENdeletion exhibits an age-dependent decline in promoting axon regeneration from the corticospinal tract (CST). How sprouting of uninjured axons, a naturally occurring form of axonal repair, is impacted by age is unknown. We assessed CST sprouting after unilateral pyramidotomy inPTENand/orSOCS3-deleted mice at different ages. WhilePTENdeletion enhances sprouting independently of age,SOCS3deletion loses its sprouting-promoting effect with age. The synergistic effect ofPTEN/SOCS3co-deletion on CST sprouting is rapidly lost with increased age. Overall, promoting sprouting appears more robust across age than regeneration, yet distinct molecular pathways are differentially impacted by age. Importantly, six-week delayedPTENdeletion promotes CST sprouting across age groups, supporting a clinically relevant time frame for this neural repair strategy independently of age.Graphical abstractDisplay OmittedHighlights•NeuronalPTENdeletion promotes robust CST axon sprouting in middle-aged mice•SOCS3deletion loses effectiveness in promoting axon sprouting in middle-aged mice•PTENandSOCS3co-deletion rapidly loses synergy with increased age•DelayedPTENdeletion in adult mice promotes CST axon sprouting across age groupsMolecular neuroscience; Cellular neuroscience
