@article{6e682cfb9e5e4d4a86cc39d427fe1a37,
title = "Diminished Schwann cell repair responses underlie age-associated impaired axonal regeneration",
abstract = "The regenerative capacity of the peripheral nervous system declines with age. Why this occurs, however, is unknown. We demonstrate that 24-month-old mice exhibit an impairment of functional recovery after nerve injury compared to 2-month-old animals. We find no difference in the intrinsic growth capacity between aged and young sensory neurons invitro or in their ability to activate growth-associated transcriptional programs after injury. Instead, using age-mismatched nerve transplants invivo, we show that the extent of functional recovery depends on the age of the nerve graft, and not the age of the host. Molecular interrogation of the sciatic nerve reveals that aged Schwann cells (SCs) fail to rapidly activate a transcriptional repair program after injury. Functionally, aged SCs exhibit impaired dedifferentiation, myelin clearance, and macrophage recruitment. These results suggest that the age-associated decline in axonal regeneration results from diminished Schwann cell plasticity, leading to slower myelin clearance.",
author = "Painter, {Michio W.} and {Brosius Lutz}, Amanda and Cheng, {Yung Chih} and Alban Latremoliere and Kelly Duong and Miller, {Christine M.} and Sean Posada and Cobos, {Enrique J.} and Zhang, {Alice X.} and Wagers, {Amy J.} and Havton, {Leif A.} and Ben Barres and Takao Omura and Woolf, {Clifford J.}",
note = "Funding Information: Confocal images were obtained using a Zeiss LSM510 Meta inverted confocal microscope through the Stanford Neuroscience Microscopy Service, supported by NIH NS069375. Funding Information: We thank David Roberson for help with figures, David Segal for assistance with behavioral experiments and setup, Olusegun Babaniyi for animal care, Giovanni Coppola for microarray data processing, David Parkinson and Xin-Peng Dun for advice on the whole-mount staining protocol, and Michael Costigan and Nadia Cohen for critical comments on the manuscript. We also thank Nick Andrews for advice on statistical analyses. This work was supported by the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (C.J.W., L.A.H., and B.B.), the Bertarelli Foundation (C.J.W.), NIH R01 NS038253 and P30 HD018655 (C.J.W.), NIH RO1 AG033053 and UO1 HL100402 (A.J.W.), NIH NRSA F31 AG042227-02 (M.W.P.), S10RR027431-01 (B.B), NIH NS069375 (B.B.), NIH T32 HD007249 Developmental and Neonatal Biology Training Program (A.B.L.), and the Stanford MSTP and School of Medicine (A.B.L.). A.J.W. is an Early Career Scientist of the Howard Hughes Medical Institute. ",
year = "2014",
month = jul,
day = "16",
doi = "10.1016/j.neuron.2014.06.016",
language = "English (US)",
volume = "83",
pages = "331--343",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "2",
}