Biology Reference
In-Depth Information
Another solution to delay the denervated atrophy of skeletal muscles is the
use of neural stem cells (NSCs); recent studies have reported that genetically
modified NSCs ameliorate experimental spinal muscular atrophy, providing
neurotrophic support or partially replacing interrupted innervation between
neural cells and skeletal muscles (
Corti et al., 2006, 2009
). Embryonic stem
cells transplanted into the spinal cord could differentiate into relatively normal
motor neurons, extend axons into periphery nerves, and form new NMJs
with denervated muscles (
Deshpande et al., 2006; Gao, Coggeshall,
Tarasenko, &Wu, 2005; Lee, Tos, et al., 2007; Lee, Jeyakumar, et al., 2007
).
Finally, local and/or systemic administration of various molecules might
also prevent skeletal muscle atrophy, such as IGF-1 (
Latres et al., 2005;
Yoshida, Semprun-Prieto, Sukhanov, & Delafontaine, 2010
) and ghrelin
(
Porporato et al., 2013
).
4. CHANGES OCCURRING PROXIMALLY TO THE
DAMAGED NERVE
4.1. Changes in the DRGs after peripheral nerve injury
and regeneration
Anatomically, the DRGs are located along the dorsal spinal roots; they house
the cell bodies of primary afferents of the spinal sensory system and are sur-
rounded by a thick connective capsule. As a consequence of a peripheral
nerve injury, trophic support from the periphery is blocked and DRG neu-
ron cell bodies undergo adaptive changes: Nissl bodies (i.e., the basophilic
neurotransmitter synthetic machinery) undergo dissolution, which is
followed by a prominent migration of the nucleus from the center of the
cell toward the periphery, an increase in the size of the nucleolus, nucleus,
and cell body, cell swelling, and retraction of dendrites, which collectively
are called “chromatolytic changes” (
Fenrich & Gordon, 2004; Lieberman,
1971
). The disappearance of the prominent basophilic-stained Nissl granules
is particularly evident. These granules are ribosome clusters of rough endo-
plasmic reticulum, that is not observed after axotomy, when they become
disorganized, freeing polyribosomes and ribonucleotides into the cytoplasm.
The severity and the time course of the chromatolytic process are mainly
influenced by the severity of the injury, the distance of lesion to cell body,
the type of neuron, and the age (
Navarro et al., 2007
).
The dissolution of the ribosomes and ordered arrays of rough endoplas-
mic reticulum that constitute the Nissl bodies are then accompanied by met-
abolic changes including overall increases in protein and mRNA synthesis as
