Biology Reference
In-Depth Information
that regenerate across the injury site, either in rats (
Seo et al., 2006
)orin
mice (
English, Schwartz, Meador, Sabatier, & Mulligan, 2007; Sabatier
et al., 2008
). The release of distinct neurotrophic factors within the spinal
cord is critical for survival of motoneurons. Although a clear relationship
between physical exercise and increased production and release of factors,
such as of leukemia inhibitory factor and ciliary neurotrophic factor
(
Dahlin & Brandt, 2004
), is lacking, other neuronal factors known to pro-
mote neuronal survival are upregulated by increased levels of physical activ-
ity. Some of these include neurotrophin (NT)-3 (
Gomez-Pinilla, Ying,
Opazo, Roy, & Edgerton, 2001; Sendtner, Pei, Beck, Schweizer, &
Wiese, 2000; Sterne, Coulton, Brown, Green, & Terenghi, 1997; Ying
et al., 2003
) and NT-4/5, glial-derived neurotrophic factor (GDNF)
(
Grumbles, Sesodia, Wood, & Thomas, 2009; Sendtner et al., 2000
),
insulin-like growth factor 1 (IGF-1) and IGF-2, and the brain-derived neu-
rotrophic factor (BDNF) (
Gomez-Pinilla et al., 2001; Wilhelm et al., 2012;
Yarrow, White, McCoy, & Borst, 2010; Ying et al., 2005
).
Motoneuron death is relatively common early during development. In
this case, GDNF is a potent rescue factor from developmentally programmed
and axotomy-related neuronal death (reviewed in
McCullough et al., 2011
).
GDNF is produced by Schwann cells and skeletal muscle, namely, after
denervation (
McCullough et al., 2011; Vianney &Spitsbergen, 2011
). Levels
of GDNF at the spinal cord tend to decrease as a consequence of peripheral
nerve injury. While treadmill exercise alone cannot revert such decrease,
when combined with electrical stimulation, it significantly raises GDNF
levels in the spinal cord following sciatic nerve cut and repair (
Cobianchi
et al., 2013
).
BDNF is particularly relevant in what concerns the effect of physical
exercise on the brain, spinal cord, and PNS. BDNF is produced and
secreted by several cell types including neurons, Schwann cells, and
muscle fibers (
Koppel et al., 2009
). Physical exercise stimulates both
nerve- and muscle-derived BDNF release and increases it circulating
levels in humans (
Gomez-Pinilla et al., 2001; Rojas Vega et al., 2006;
Yarrow et al., 2010; Ying et al., 2003
). However, the BDNF system
is not always neuroprotective. Unlike mature BDNF, proBDNF protein,
acting through the p75
NTR
neurotrophic receptor, is proapoptotic and
causes synaptic regression (
Teng et al., 2005
). Importantly, wheel running
enhances the synthesis of mature BDNF from proBDNF in mice,
through activation of tissue-type plasminogen activator (
Ding, Ying, &
Gomez-Pinilla, 2011
).
