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JAMES A. CARSON, PhD
Carmichael MD, Davis JM, Murphy EA, Brown
AS, Carson JA, Mayer E, Ghaffar A. Recovery of running
performance following muscle-damaging exercise: Relationship
to brain IL-1beta. Brain Behav Immun. 2005 May 20
Recovery following muscle-damaging downhill running is
associated with increased muscle inflammatory cytokines.
Various inflammatory challenges can also increase cytokines
in the brain, which have been linked to sickness behaviors,
including fatigue, but little is known about the brain
cytokine response to stressful exercise. We used a downhill
running model to determine the relationship between brain
IL-1beta and recovery of running performance. Male C57BL/6
mice were assigned to: downhill (DH), uphill (UH), or
non-running control (Con) groups and run on a treadmill at
22m/min and -14% or 14% grade, for 150min. Following the
run, a subset of DH and UH was placed into activity wheel
cages where voluntary running activity was measured for 7
days. A second subset was run to fatigue on a motorized
treadmill at 36m/min, 8% grade at 24, 48, and 96h
post-up/downhill run. A third subset of DH, UH, and Con mice
had brains dissected and assayed for IL-1beta at 24 and 48h.
DH resulted in delayed recovery of both voluntary
wheel-running and treadmill running to fatigue as compared
to UH (p<.05). DH was also associated with increased
IL-1beta concentrations in cortex (at 24 and 48h) and
cerebellum (24h) as compared to UH and Con. UH was not
different than Con in any brain region. Eccentric-biased
downhill running results in an increase in plasma CK and
delayed recovery in running performance, as compared to the
more metabolically demanding uphill running, and this was
associated with increased concentrations of IL-1beta in
regions of the brain responsible for movement, coordination,
motivation, perception of effort, and pain.
Mehl KA, Davis JM, Clements JM, Berger FG, Pena MM, Carson
JA. Decreased intestinal polyp multiplicity is related to
exercise mode and gender in ApcMin/+ mice. J Appl Physiol.
2005 Jun;98(6):2219-25
Moderate-intensity treadmill running can alter male Apc(Min/+)
mouse polyp formation. This purpose of this study was to
examine whether exercise mode differentially affects Apc(Min/+)
mouse intestinal polyp development in male and female mice.
Male and female Apc(Min/+) mice were randomly assigned to
control, treadmill (18 m/min; 60 min/day; 6 days/wk), or
voluntary wheel running (24-h access) groups. Nine weeks of
training decreased total intestinal polyps by 29% in male
treadmill runners (66 +/- 9; P = 0.038) compared with male
controls (93 +/- 7). The number of large polyps (>/=1-mm
diameter) were also reduced by 38% in male treadmill runners
(49 +/- 6; P = 0.005) compared with male controls (79 +/-
6). Treadmill running in female Apc(Min/+) mice and wheel
running in both genders did not affect polyp number or size.
Spleen weight decreased in male treadmill runners (91 +/- 9
mg; P = 0.011) and wheel runners (75 +/- 6 mg; P = 0.004)
compared with controls (141 +/- 13 mg). Plasma IL-6 was
reduced by 96% in male treadmill runners (1.2 +/- 0.6 pg/ml)
and 78% in male wheel runners (6.6 +/- 3.3 pg/ml) compared
with control mice (27.9 +/- 2.8 pg/ml; P < 0.05). Female
mice responded similarly with an 86% decrease in plasma IL-6
with treadmill running (3.2 +/- 1.2 pg/ml) and 90% decrease
with wheel running (2.9 +/- 2.0 pg/ml) compared with control
mice (21.1 +/- 5.3 pg/ml; P < 0.05). The crypt depth-to-villus
height ratio in the intestine, an indirect marker of
intestinal inflammation, decreased by 21 (P = 0.024) and 24%
(P = 0.029), respectively, in male and female treadmill
runners but not wheel runners. Physical activity-induced
attenuation of intestinal polyp number and size is dependent
on exercise mode and differs between genders. The modulation
of systemic and intestinal inflammation may also depend on
exercise mode.
McClung JM, Mehl KA, Thompson RW, Lowe LL, Carson JA.
Nandrolone decanoate modulates cell cycle regulation in
functionally overloaded rat soleus muscle. Am J Physiol
Regul Integr Comp Physiol. 2005 Jun;288(6):R1543-52
Functionally overloading rat soleus muscle by synergist
ablation induces a rapid increase in mass. Muscle remodeling
during the first week of overload is critical for the
overload-induced growth. Anabolic steroid modulation of this
overload-induced remodeling response is not well understood.
The purpose of this study was to determine whether
pretreatment with nandrolone decanoate, a clinically
administered anabolic steroid, alters muscle morphology and
gene expression related to muscle growth during the
initiation of functional overload in the rat soleus muscle.
Adult (5 mo) male Fisher 344 x Brown Norway rats were
randomly assigned to control (Sham), 3-day functional
overload (OV), nandrolone decanoate administration (ND), or
3-day functional overload with nandrolone decanoate
administration (OV+ND) treatment groups. Morphologically, OV
increased the percentage of small (361%) and large (150%)
fibers and expanded the ECM 50%. ND administration decreased
the 3-day OV induction of small fibers 51% and nuclei
associated with the ECM 20%. ND administration also
attenuated the induction of cell cycle regulator p21 (64%)
and myogenin (37%) mRNAs after 3 days of overload. These
data demonstrate that nandrolone decanoate pretreatment can
alter morphological and cell cycle regulator expression
related to muscle growth at the onset of functional
overload.
Washington TA, Reecy JM, Thompson RW, Lowe LL, McClung JM,
Carson JA. Lactate dehydrogenase expression at the onset of
altered loading in rat soleus muscle. J Appl Physiol. 2004
Oct;97(4):1424-30
Both functional overload and hindlimb disuse induce
significant energy-dependent remodeling of skeletal muscle.
Lactate dehydrogenase (LDH), an important enzyme involved in
anaerobic glycolysis, catalyzes the interconversion of
lactate and pyruvate critical for meeting rapid high-energy
demands. The purpose of this study was to determine rat
soleus LDH-A and -B isoform expression, mRNA abundance, and
enzymatic activity at the onset of increased or decreased
loading in the rat soleus muscle. The soleus muscles from
male Sprague-Dawley rats were functionally overloaded for up
to 3 days by a modified synergist ablation or subjected to
disuse by hindlimb suspension for 3 days. LDH mRNA
concentration was determined by Northern blotting, LDH
protein isoenzyme composition was determined by zymogram
analysis, and LDH enzymatic activity was determined
spectrophotometrically. LDH-A mRNA abundance increased by
372%, and LDH-B mRNA abundance decreased by 43 and 31% after
24 h and 3 days of functional overload, respectively,
compared with that in control rats. LDH protein expression
demonstrated a shift by decreasing LDH-B isoforms and
increasing LDH-A isoforms. LDH-B activity decreased 80%
after 3 days of functional overload. Additionally, LDH-A
activity increased by 234% following 3 days of hindlimb
suspension. However, neither LDH-A or LDH-B mRNA abundance
was affected following 3 days of hindlimb suspension. In
summary, the onset of altered loading induced a differential
expression of LDH-A and -B in the rat soleus muscle,
favoring rapid energy production. Long-term altered loading
is associated with myofiber conversion; however, the rapid
changes in LDH at the onset of altered loading may be
involved in other physiological processes.
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