Biology Reference
In-Depth Information
macrophages to aid the removal of axonal and myelin debris (
Bruck, 1997;
Vargas & Barres, 2007
). Fragmentation of axons is first detected few hours
after nerve transection. Within 48 h, the entire nerve is fully involved, and
over a period of 3-6 weeks, Schwann cells and macrophages phagocytize
all the myelin and cellular debris.
Schwann cells play several important roles in nerve degeneration and
regeneration:
i.
Coincident with axonal injury, Schwann cells in the distal nerve begin
to dedifferentiate (
Lee et al., 2009
). Within 48 h of injury, they start
altering their gene expression: expression of myelin proteins (e.g.,
P0, MAG (myelin-associated glycoprotein)) (
Trapp, Hauer, &
Lemke, 1988; White et al., 1989
) and connexin 32 (a gap junction pro-
tein which forms reflexive contacts within individual myelinating SCs
at para-nodes) (
Hall, 2001
) decreases dramatically as a consequence of
axonal degeneration distal to the injury site, whereas regeneration-
associated genes (GAP-43), neurotrophic factors and their receptors,
neurotrophin 4/5 (NT-4/5) neuregulin and its receptors, including
the low-affinity neurotrophin receptor p75NTR; nerve growth factor
(NGF), brain-derived neurotrophic factor (BDNF), glial cell line-
derived neurotrophic factor (GDNF), and insulin-like growth factors
(IGFs) (
Carroll, Miller, Frohnert, Kim, & Corbett, 1997; Hall, 2001
)
are upregulated.
ii.
Between days 1 and 5 after injury, Schwann cells start proliferating, a
critical event for the promotion of axonal regeneration. Their peak of
activation occurs around day 3 postinjury and then decreases during the
following weeks. A second phase of proliferation occurs during the
regenerative process. Proliferating Schwann cells align in columns
known as bands of B¨ngner, which provide a supportive substrate
and growth factors for regenerating axons (
Griffin & Thompson,
2008; Stoll, Griffin, Li, & Trapp, 1989
).
iii.
Schwann cells also play an important role in removing myelin debris;
rapid clearance of myelin appears to be the most important precondi-
tion for axonal regeneration after peripheral nerve injury because it
contains molecules that are inhibitory to axonal growth, such as
MAG and oligodendrocyte-myelin glycoprotein (
Huang et al., 2005;
Shen et al., 2000
).
iv.
Yet, Schwann cells in the distal nerve stump produce several neuro-
trophic and neurotropic molecules (such as NGF, BDNF, NT-4,
GDNF, and insulin-like growth factor-1 (IGF-1)) that promote axon
