...but lordy it's hard. In case you needed inspiration to exercise.

Exercise has dramatic effects on BDNF. And so does lack of it.


1: J Neurophysiol. 2002 Nov;88(5):2187-95.

Voluntary exercise induces a BDNF-mediated mechanism that promotes
neuroplasticity.

Gomez-Pinilla F, Ying Z, Roy RR, Molteni R, Edgerton VR.

Department of Physiological Science, Los Angeles, California 90095, USA.
fgomezpi@ucla.edu

We have investigated potential mechanisms by which exercise can promote changes
in neuronal plasticity via modulation of neurotrophins. Rodents were exposed to
voluntary wheel running for 3 or 7 days, and their lumbar spinal cord and soleus
muscle were assessed for changes in brain-derived neurotrophic factor (BDNF),
its signal transduction receptor (trkB), and downstream effectors for the action
of BDNF on synaptic plasticity. Exercise increased the expression of BDNF and
its receptor, synapsin I (mRNA and phosphorylated protein), growth-associated
protein (GAP-43) mRNA, and cyclic AMP response element-binding (CREB) mRNA in
the lumbar spinal cord. Synapsin I, a synaptic mediator for the action of BDNF
on neurotransmitter release, increased in proportion to GAP-43 and trkB mRNA
levels. CREB mRNA levels increased in proportion to BDNF mRNA levels. In
separate experiments, the soleus muscle was paralyzed unilaterally via
intramuscular botulinum toxin type A (BTX-A) injection to determine the effects
of reducing the neuromechanical output of a single muscle on the neurotrophin
response to motor activity. In sedentary BTX-A-treated rats, BDNF and synapsin I
mRNAs were reduced below control levels in the spinal cord and soleus muscle.
Exercise did not change the BDNF mRNA levels in the spinal cord of BTX-A-treated
rats but further reduced the BDNF mRNA levels in the paralyzed soleus relative
to the levels in sedentary BTX-A-treated rats. Exercise also restored synapsin I
to near control levels in the spinal cord. These results indicate that basal
levels of neuromuscular activity are required to maintain normal levels of BDNF
in the neuromuscular system and the potential for neuroplasticity.

PMID: 12424260 [PubMed - indexed for MEDLINE]

1: Neuroscience. 2004;124(4):985-92.

Voluntary exercise protects against stress-induced decreases in brain-derived
neurotrophic factor protein expression.

Adlard PA, Cotman CW.

Institute for Brain Aging and Dementia, 1113 Gillespie N.R.F., University of
California, Irvine, Irvine, CA 92697-4540, USA. padlard@uci.edu

Exercise is increasingly recognized as an intervention that can reduce CNS
dysfunctions such as cognitive decline, depression and stress. Previously we
have demonstrated that brain-derived neurotrophic factor (BDNF) is increased in
the hippocampus following exercise. In this study we tested the hypothesis that
exercise can counteract a reduction in hippocampal BDNF protein caused by acute
immobilization stress. Since BDNF expression is suppressed by corticosterone
(CORT), circulating CORT levels were also monitored. In animals subjected to 2 h
immobilization stress, CORT was elevated immediately following, and at 1 h after
the cessation of stress, but remained unchanged from baseline up to 24 h
post-stress. The stress protocol resulted in a reduction in BDNF protein at 5
and 10 h post-stress that returned to baseline at 24 h. To determine if exercise
could prevent this stress-induced reduction in BDNF protein, animals were given
voluntary access to running wheels for 3 weeks prior to the stress. Stressed
animals, in the absence of exercise, again demonstrated an initial elevation in
CORT (at 0 h) and a subsequent decrease in hippocampal BDNF at the 10 h time
point. Exercising animals, both non-stressed and stressed, demonstrated
circulating CORT and hippocampal BDNF protein levels that were significantly
elevated above control values at both time points examined (0 and 10 h
post-stress). Thus, the persistently high CORT levels in exercised animals did
not affect the induction of BDNF with exercise, and the effect of immobilization
stress on BDNF protein was overcome. To examine the role of CORT in the
stress-related regulation of BDNF protein, experiments were carried out in
adrenalectomized (ADX) animals. BDNF protein was not downregulated as a result
of immobilization stress in ADX animals, while there continued to be an
exercise-induced upregulation of BDNF. This study demonstrates that CORT
modulates stress-related alterations in BDNF protein. Further, exercise can
override the negative effects of stress and high levels of CORT on BDNF protein.
Voluntary physical activity may, therefore, represent a simple
non-pharmacological tool for the maintenance of neurotrophin levels in the
brain.

PMID: 15026138 [PubMed - indexed for MEDLINE]

1: Neuroscience. 2004;123(2):429-40.

Exercise reverses the harmful effects of consumption of a high-fat diet on
synaptic and behavioral plasticity associated to the action of brain-derived
neurotrophic factor.

Molteni R, Wu A, Vaynman S, Ying Z, Barnard RJ, Gomez-Pinilla F.

Department of Physiological Science, Brain Injury Research Center, University of
California at Los Angeles, 621 Charles E. Young Drive, Los Angeles, CA 90095,
USA.

A diet high in total fat (HF) reduces hippocampal levels of brain-derived
neurotrophic factor (BDNF), a crucial modulator of synaptic plasticity, and a
predictor of learning efficacy. We have evaluated the capacity of voluntary
exercise to interact with the effects of diet at the molecular level. Animal
groups were exposed to the HF diet for 2 months with and without access to
voluntary wheel running. Exercise reversed the decrease in BDNF and its
downstream effectors on plasticity such as synapsin I, a molecule with a key
role in the modulation of neurotransmitter release by BDNF, and the
transcription factor cyclic AMP response element binding protein (CREB),
important for learning and memory. Furthermore, we found that exercise
influenced the activational state of synapsin as well as of CREB, by increasing
the phosphorylation of these molecules. In addition, exercise prevented the
deficit in spatial learning induced by the diet, tested in the Morris water
maze. Furthermore, levels of reactive oxygen species increased by the effects of
the diet were decreased by exercise. Results indicate that exercise interacts
with the same molecular systems disrupted by the HF diet, reversing their
effects on neural function. Reactive oxygen species, and BDNF in conjunction
with its downstream effectors on synaptic and neuronal plasticity, are common
molecular targets for the action of the diet and exercise. Results unveil a
possible molecular mechanism by which lifestyle factors can interact at a
molecular level, and provide information for potential therapeutic applications
to decrease the risk imposed by certain lifestyles.

PMID: 14698750 [PubMed - indexed for MEDLINE]

1: Neuroscience. 2005;133(3):853-61.

Exercise primes a molecular memory for brain-derived neurotrophic factor protein
induction in the rat hippocampus.

Berchtold NC, Chinn G, Chou M, Kesslak JP, Cotman CW.

Institute for Brain Aging and Dementia, 1226 Gillespie Neuroscience Facility,
University of California, Irvine, CA 92697-4540, USA. nberchto@uci.edu

Exercise is an important facet of behavior that enhances brain health and
function. Increased expression of the plasticity molecule brain-derived
neurotrophic factor (BDNF) as a response to exercise may be a central factor in
exercise-derived benefits to brain function. In rodents, daily wheel-running
exercise increases BDNF gene and protein levels in the hippocampus. However, in
humans, exercise patterns are generally less rigorous, and rarely follow a daily
consistency. The benefit to the brain of intermittent exercise is unknown, and
the duration that exercise benefits endure after exercise has ended is
unexplored. In this study, BDNF protein expression was used as an index of the
hippocampal response to exercise. Both daily exercise and alternating days of
exercise increased BDNF protein, and levels progressively increased with longer
running duration, even after 3 months of daily exercise. Exercise on alternating
days was as effective as daily exercise, even though exercise took place only on
half as many days as in the daily regimen. In addition, BDNF protein remained
elevated for several days after exercise ceased. Further, after prior exercise
experience, a brief second exercise re-exposure insufficient to cause a BDNF
change in naive animals, rapidly reinduced BDNF protein to levels normally
requiring several weeks of exercise for induction. The protein reinduction
occurred with an intervening "rest" period as long as 2 weeks. The rapid
reinduction of BDNF by an exercise stimulation protocol that is normally
subthreshold in naive animals suggests that exercise primes a molecular memory
for BDNF induction. These findings are clinically important because they provide
guidelines for optimizing the design of exercise and rehabilitation programs, in
order to promote hippocampal function.