THESIS
2013
iii leaves, iv-xii, 71 pages : illustrations (some color) ; 30 cm
Abstract
Unlike the central nerve system (CNS), in the peripheral nervous system (PNS),
neurons can regenerate their axons and reinnervate their targets. However, functional
recovery often remains suboptimal. In this work, we investigated the role of PTEN-mTOR
pathway during regeneration of peripheral neuronal axons in mice. We find that
mTOR activity responds differently to injury in CNS and PNS. By deletion of PTEN,
axonal growth capacity of PNS dorsal root ganglial neurons (DRGs) is enhanced both in
vitro and in vivo. We also find that the enhanced axonal growth capacity of DRGs by
PTEN knock out and conditioning lesion is independent of mTOR, while inhibiting
PI3K and AKT activity can partially block both conditioning lesion effect and PTEN
knock out induced growth. However just by...[
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Unlike the central nerve system (CNS), in the peripheral nervous system (PNS),
neurons can regenerate their axons and reinnervate their targets. However, functional
recovery often remains suboptimal. In this work, we investigated the role of PTEN-mTOR
pathway during regeneration of peripheral neuronal axons in mice. We find that
mTOR activity responds differently to injury in CNS and PNS. By deletion of PTEN,
axonal growth capacity of PNS dorsal root ganglial neurons (DRGs) is enhanced both in
vitro and in vivo. We also find that the enhanced axonal growth capacity of DRGs by
PTEN knock out and conditioning lesion is independent of mTOR, while inhibiting
PI3K and AKT activity can partially block both conditioning lesion effect and PTEN
knock out induced growth. However just by knocking out PTEN is not sufficient to
enhance the sensory recovery of the mice. Overall, these findings identify the difference
in intrinsic regenerative mechanisms between CNS and PNS, and manipulation and fine
control of PTEN-mTOR pathway are needed to benefit nerve repair.
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