THESIS
2015
iii leaves, iv-ix, 54 pages : illustrations (some color) ; 30 cm
Abstract
Different from neurons in the central nervous system, adult neurons in the
mammalian peripheral nervous system can regenerate axons after injury
partially by enhancing the intrinsic growth capacity. A conditioning lesion prior to
the injury further enhances the regeneration. Previous studies about the roles of
mammalian target of rapamycin complex 1 in affecting axon growth of neurons in
dorsal root ganglions (DRGs) were controversial. Here we report that peripheral
axotomy to dorsal root ganglions (DRGs) enhances AKT/mTOR activity, and
PTEN deletion can partially mimic this growth promoting effect. Both
pharmacological and genetic evidence indicate that PI3K/AKT/mTOR pathway is
required for sensory axon regeneration. Moreover, we provide genetic evidence
that mTORC1 is indisp...[
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Different from neurons in the central nervous system, adult neurons in the
mammalian peripheral nervous system can regenerate axons after injury
partially by enhancing the intrinsic growth capacity. A conditioning lesion prior to
the injury further enhances the regeneration. Previous studies about the roles of
mammalian target of rapamycin complex 1 in affecting axon growth of neurons in
dorsal root ganglions (DRGs) were controversial. Here we report that peripheral
axotomy to dorsal root ganglions (DRGs) enhances AKT/mTOR activity, and
PTEN deletion can partially mimic this growth promoting effect. Both
pharmacological and genetic evidence indicate that PI3K/AKT/mTOR pathway is
required for sensory axon regeneration. Moreover, we provide genetic evidence
that mTORC1 is indispensible for axon regeneration in DRGs induced by either
PTEN deletion or conditioning lesion. In addition, we find that Stat3 activation
is also necessary for DRG axon growth, and predict mTORC1 can regulate the
activation of Stat3. In a word, our study provide the genetic evidence that
mTORC1 is required for axon growth in DRG neurons, and suggest some new
interactions between PTEN-mTOR and JAK-STAT pathways.
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