Biology Reference
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of PTEN-deleted RGCs overcome the growth-inhibitory environment
(i.e., chondroitin sulfate proteoglycan (CSPG)-rich region) in the lesion site,
regenerating over long distances in the degenerated optic nerve (
Park et al.,
2008
). The corticospinal tract (CST) that controls voluntary movements is
particularly important for functional recovery after spinal cord injury.
Injured CST axons are particularly refractory to regeneration, and efforts to
promote regenerative growth of CST axons in animal injury models have
yielded only limited success (
Lee et al., 2010; Zheng et al., 2005
).
Liu et al.
(2010)
demonstrated using adeno-associated virus (AAV) expressing Cre
recombinase that deletion of PTEN in corticospinal neurons promotes
substantial axon regrowth following spinal cord injury. In this study, several
injury models including pyramidotomy, dorsal hemisection, and complete
crush were utilized to demonstrate that PTEN deletion in CST neurons
enhance axon sprouting/plasticity (axon growth from uninjured, spared
neurons) and regeneration (axon growth from axotomized neurons).
Further, immunohistochemical and electron microscopic analysis showed
that regenerated axons in the spinal cord of PTEN-deleted animals
reformed synapse-like structures distal to the injury site (
Liu et al., 2010
).
The inhibitory role of PTEN on axon growth was also shown in cortical
neurons using
in vitro
assays. Cultured cortical neurons exhibit limited
neurite outgrowth when plated on myelin-associated glycoprotein (MAG)-
expressing substrate cells (
Perdigoto, Chaudhry, Barnes, Filbin, & Carter,
2011
). Deletion or knockdown of PTEN in cortical neurons using
knockout mice or short hairpin RNAs (shRNAs) resulted in enhanced
neurite outgrowth when the neurons are plated on MAG-substrate cells.
On the other hand, PTEN inactivation did not affect neurite outgrowth
when the cortical neurons were plated on non-MAG expressing control
cells (
Perdigoto et al., 2011
), suggesting that PTEN contributes to the
growth-inhibitory signal resulting from MAG.
Outside of the CNS, PTEN was also shown to affect axon regeneration
in the PNS. Dorsal root ganglia (DRG) neurons are able to regenerate pe-
ripheral, but not central branches in the adult spinal cord. However, a
preconditioning lesion to the peripheral branches allows the subsequently in-
jured central branches to grow into and beyond a lesion site (
Bisby & Pollock,
1983; Hoffman, 2010; McQuarrie, Grafstein, & Gershon, 1977; Neumann &
Woolf, 1999; Richardson & Issa, 1984
). This preconditioning model has been
an invaluable tool to study the intrinsic mechanisms that allow enhanced
regenerative ability in neurons. Inhibition of PTEN activity led to
significant increase in neurite outgrowth for both un-preconditioned and
