E-Mail [email protected] Review Neuropsychobiology 2013;68:114
DOI: 10.1159/000350946 Neuroscience of Exercise: FromNeurobiology
Mechanisms toMentalHealth
EduardoMattaMelloPortugalacThaisCevadaa,dRenatoSobralMonteiro-Juniora,b,e
ThiagoTeixeiraGuimaresaErcoledaCruzRubinia,e,h,iEduardoLattaria,b
CharleneBloisa,f,gAndreaCamazDeslandesa,b aNeuroscience
Laboratory of Exercise, UGF,bExercise and Sport Sciences Graduate
Program, Gama Filho University,UGF, cPerformance Research Group,
UGF,dInstitute of Psychiatry of the Federal University of Rio de
Janeiro, IPUB/UFRJ, eClinicSchool of Physiotherapy, UGF,fFederal
University of Rio de Janeiro, UFRJ,gBiometry Laboratory, Federal
University of Rio de Janeiro, UFRJ,hPhysical Education Course,
University Estcio de S, andiLaboratory of Physical Activity and
Health Promotion, LABSAU/UERJ,Rio de Janeiro , Brazil mental health
of athletes. Exercise is associated with the in-creased synthesis
and release of both neurotransmitters and
neurotrophicfactors,andtheseincreasesmaybeassociat-ed
withneurogenesis,angiogenesisandneuroplasticity. This review is a
call-to-action that urges researchers to con-sider the importance
of understanding the neuroscience of physical exercise and its
contributions to sports science. Copyright 2013 S. Karger AG, Basel
Men ought to know that from nothing else but the brain come joys,
delights, laughter and sports, grief, despondency, and lamentation.
Hippocrates , 400 BC Introduction Neuroscience is a growing
research area comprising a variety of multidisciplinary
investigations that seek to un-derstand the relationship between
the body and the brain. At the beginning of the previous century,
our knowledge of the correlation between neuroscience and exercise
was Key Words Neurobiology of exercise Depression Adherence
Physical training Mood Abstract
Theneuroscienceofexerciseisagrowingresearcharea thatis dedicated to
furthering our understanding of the ef-fects that exercise has on
mental health and athletic
perfor-mance.Thepresentstudyexaminedthreespecifictopics: (1)the
relationship between exercise and mental disorders
(e.g.majordepressivedisorder,dementiaandParkinsons disease), (2)
the effects of exercise on the mood and mental
healthofathletes,and(3)thepossibleneurobiological mechanisms that
mediate the effects of exercise. Positive re-sponses to regular
physical exercise, such as enhanced
func-tionalcapacity,increasedautonomyandimprovedself-es-teem, are
frequently described in the recent literature, and these responses
are all good reasons for recommending
reg-ularexercise.Inaddition,physicalexercisemayimprove both mood
and adherence to an exercise program in healthy individuals and
might modulate both the performance and Received: September 28,
2012 Accepted after revision: March 24, 2013 Published online: June
15, 2013 Eduardo Matta Mello Portugal, MSc Programa de Ps Graduao
Stricto Sensu em Cincias do Exerccio e do Esporte da Universidade
Gama Filho, Rua Manoel Vitorino 553 Piedade, Rio de Janeiro, RJ
20748-900 (Brazil) E-Mail [email protected] 2013 S. Karger
AG, Basel0302282X/13/06810001$38.00/0 www.karger.com/nps Downloaded
by: 198.143.56.33 - 6/22/2015 7:51:51 AM MattaMelloPortugaletal.
Neuropsychobiology 2013;68:114DOI:
10.1159/0003509462acquiredprimarilythroughstudiesthatinvestigatedthe
effectsofcertainsubstances(e.g.ammonia)andthehe-modynamic responses
to them on brain function and fa-tigue [1, 2] . The effects of
physical exercise on the struc-tures and functions (i.e.
physiological, psychological and
biochemical)ofthecentralnervoussystem(CNS)have received increasing
attention from the scientific
commu-nity,inthecontextofboththepotentialmentalhealth benefits for
clinical populations and potential sports sci-ence applications,
and these effects have been examined in studies of the exercise
adherence, mental health and ath-lete performance [36] . For
example, Pires [3] has shown that there is a growing number of
citations for studies that investigate the central governor model
and exercise. Studies of the efficacy of using exercise to treat
and/or preventmentaldisordersareessential,particularlygiven the
fast-growing elderly population and the consequent rise
intheprevalenceofneurodegenerativeillnessesandde-pression. Recent
increases in the incidences of several
men-taldisorders,suchasmajordepressivedisorder(MDD) [7] ,
dementia[8] and Parkinsons disease (PD) [9] , high-light the
necessity of increasing research efforts that focus on identifying
treatments that can improve an individuals
mentalhealth.Althoughpharmacologicaltherapyisthe current gold
standard for the treatment of all mental dis-eases, the possible
adverse effects of medication contribute to failures in patient
compliance. Therefore, both reducing the costs of medications and
hospitalizations and enhanc-ing the quality of life of mental
health patients should be prioritized. A recent review published by
members of our laboratory showed that regular exercise reduces the
symp-toms of MDD, dementia and PD [5]. Thus, exercise can be an
adjuvant treatment for several mental diseases. One
pos-sibleneurobiologicalmechanismunderlyingthepositive effects of
exercise is the increased synthesis and release of
neurotransmitters and neurotrophins, which could result
inneurogenesis,angiogenesisandneuroplasticity [10] . Nonetheless,
more information regarding the neurological effects of exercise in
a clinical sample is needed. Even though there is strong evidence
that exercise has positive effects on mental health and cognition,
these out-comesaredependentonregularexercisepractice [11] .
Thehighratesofphysicalinactivitymakeitdifficultto achieve the
benefits of exercise [12] . In this context,
Wil-liamsetal.[13]havefoundthattheacuteaffectivere-sponse to
exercise is an important determinant of exercise
adherenceviacognitive(i.e.perceivedautonomyand self-efficacy) and
interoceptive (i.e. lactate accumulation
andbloodpH)pathways.Therefore,giventhemodula-tion of adherence by
the acute affective response to exer-cise, which is dependent on
the exercise setting, the opti-mal prescription should be
determined. Although regular exercise has the potential to promote
mental health, an excessive level of exercise can have ad-verse
effects, such as overtraining [14] . In addition to exer-cise,
other factors associated with a high level of pressure to perform
well and other stressors, contribute to the high
prevalenceofmentaldisordersamongeliteathletes[15] .
Pharmacologicaltreatmentiswellacceptedforthetreat-ment of
athletes[16] , although other strategies, such as in-creased energy
intake and decreased energy expenditure, are also necessary [17] .
Thus, the control of psychological variables, combined with
physiological variables, is
essen-tialtothesuccessofanathlete.Corroboratingthisargu-ment,Noakes[4]arguesthatduringenduranceevents,
structures in the CNS have an important function in deter-mining
the strategies that are used to limit exercise efforts and preserve
the health of the athlete, and these structures play a role in the
modulation of other body systems during exercise, ultimately
contributing to improved performance. Considering the importance of
knowledge about the re-lationship between exercise and the broad
context of neu-roscience involved in mental health, along with
adherence to exercise programs, performance and the diversity of
the variables analyzed in these studies, we conducted a
com-prehensive review to identify the current state of the art in
the field of the neuroscience of exercise. Thus, the effects of
exercise on physiological, psychological and
biochemi-calvariablesrelatedtoCNSstructureandfunctionwere analyzed.
Our study began by examining the relationships between exercise and
the most prevalent mood disorders and neurodegenerative diseases.
However, it is also worth discussing the acute effects that
exercise has on mood and
adherencetoanexerciseprogram.Moreover,whatpro-tects the mind does
not always protect the body; diagnoses
ofvariousmentaldisordersaresurprisinglycommon among athletes who
have been subjected to overtraining, fatigue, competition-related
stress, injuries, failure and
re-tirement.Thus,thebrainmaycontributetodiminished performance or
increased fatigue in some circumstances. The final section of this
article examines a neurobiological hypothesis that may explain the
mechanisms that underlie the effects of exercise on mental health.
Mental Disorders and Neurodegenerative Disorders Major Depressive
Disorder Data from the World Health Organization [18] provide
evidenceofacausalrelationshipbetweenMDDandthe Downloaded by:
198.143.56.33 - 6/22/2015 7:51:51 AM Neuroscience of
ExerciseNeuropsychobiology 2013;68:114DOI:
10.1159/0003509463subsequent development of a disability, and some
diseas-es that have MDD as a comorbidity are associated with a
diminished Mean Health Score[18] . There is a relation-ship among
morbidity due to this disease, aging, the num-ber of systemic
illnesses and a lack of physical exercise [7] . Several hypotheses
regarding the mechanisms that
un-derliethepathophysiologyofMDDhavebeenstudied. The most popular
theory involves the activity of mono-amines, namely reductions in
the activities of serotonin and norepinephrine[19] . Another
mechanism involved
indepressionisthehyperactivityofthehypothalamic-pituitary-adrenal
axis due to the increased release of cor-tisol and
corticotropin-releasing factor [20] . The effect of exercise, as an
adjunct to pharmacologi-cal treatment, on depressive symptoms has
been studied [5, 21]. Follow-up studies, clinical trials and
randomized controlled trials have found evidence of a positive
corre-lation between regular physical exercise and a reduction in
depressive symptoms[2125] . Both strength training and aerobic
training have positive effects in the treatment of depression[25] .
Furthermore, high-intensity strength training (80% of one maximum
workload lifted (1 repeti-tionmaximum(RM)) [23]
,moderateaerobictraining (17kcal/kg/min)[22] and supervised
moderate-intensity training(7080%HRR) [21]wereallshowntoinduce
positive responses in an investigation of the effect of ex-ercise
on depressive symptoms. In contrast, Krogh et al. [26] have
observed the opposite pattern of results in a
re-centmeta-analysis.Theyconcludedthatexercisehas
smallshort-termeffectsontheseverityofdepressive symptoms but that
the existing data regarding the long-term effects of exercise are
inconclusive. The lack of in-clusion criteria, even for studies of
good quality, can ex-plain these results. Using rigorous inclusion
criteria, our groupperformedameta-analysis [25]thatshowedthat both
aerobic exercise and strength training have positive
effectsondepressivesymptoms.Theseeffectsaresub-stantialinelderlyindividualsandindividualswhohave
mild depressive symptoms [25] .
Itappearsthattheefficacyofusingexercisetoreduce the severity of
depressive symptoms depends on the level of adherence to an optimal
exercise regimen; a combina-tion of moderate-intensity aerobic
training and
high-inten-sitystrengthtrainingmayprovidemorepositivebenefits
thanotherexerciseprograms.Neurobiologicalmecha-nisms can explain
these positive effects (see the Neurobiol-ogy of Exercise section).
However, there are both
method-ologicallimitations(i.e.lackofstatisticallysignificant
results, poor sample selection criterion and MDD diagnos-tics,no
adequate control of exercise regimen) that limit our understanding
of this observation. In summary, more re-search is necessary to
better understand the effects of exer-cise on the depressive
symptoms of MDD patients. Dementia
Dementiaisthemostprevalentneurodegenerative disease worldwide. In a
review study it was estimated that
24.3millioncaseshavebeenreported,and4.6million new cases are
reported annually in the world [27] . Despite the heterogeneity of
its symptoms, dementia is associated
withtheprogressivelossofvariouscognitivefunctions and the
consequent impairment of an individuals ability to perform daily
life activities. Mental stimulation, prop-er nutrition and exercise
appear to exert both prophylac-tic and therapeutic effects on the
development and pro-gression of neurodegenerative dementia[2830] .
Physi-cal activity alone is associated with a 28% reduction in an
individuals risk of developing the disease [31] . Given the
possible adverse effects related to
pharma-cologicaltreatment,thequalityoflifeandthegeneral well-being
of individuals who suffer from dementia can be compromised [32] .
Thus, it is important to investigate
alternative,non-pharmacologicaltreatmentstrategies such as exercise
[33] . A meta-analysis conducted by Hein et al.[32] found that
regular exercise performed with the mean training duration from all
studies of 23 weeks, with a range of 2112 weeks, had positive
effects on both cog-nitive and behavioral improvement. There was an
aver-age of 3.6 sessions per week, ranging from 1 to 6 sessions,
with each session lasting an average of 45 min (mean) and ranging
from 20 to 150 min. However, Forbes et al.[34]
concludethatthereisnotsufficientevidencetodeter-mine whether
participation in a regular exercise program actually benefits
people with dementia. The inconclusive
resultsoftheirstudymayhavebeenobtainedbecause these authors chose
criteria for assessing the methodolog-ical quality of existing
studies that resulted in the inclu-sion of only two studies in
their meta-analysis. There is some evidence that exercise can
improve cog-nitivefunction,theabilitytoperformdailylifeactivities
and the ability to walk in dementia patients, but both the
lowintensitiesoftheprescribedexerciseregimensthat were used in the
studies that Forbes et al.[34] reviewed and the methodological
qualities of those studies can be criti-cized. For example, a
recent study examined 62 dementia
patientswhounderwent3monthsofprogressiveresis-tance and functional
group training. The resistance train-ing targeted functionally
relevant muscle groups at a sub-maximal intensity (7080% of 1RM)
and was performed in groups of 46 participants for 3 months (2 h,
twice a week). Downloaded by: 198.143.56.33 - 6/22/2015 7:51:51 AM
MattaMelloPortugaletal. Neuropsychobiology 2013;68:114DOI:
10.1159/0003509464This study found evidence of increases in both
the strength and functional capacities of the treated patients that
were not observed among the patients in the control group [35] .
Alzheimersdisease(AD)isthemostprevalentform
ofdementiaandisassociatedwiththeaccumulationof
senileplaquesandneurofibrillarytanglesthatresultin the atrophy of
the hippocampus. Data from animal mod-els suggest that in the
animal strains that have been stud-ied, physical exercise is
associated with a reduction in the formation of -amyloid deposits
and the enhanced clear-ance of these deposits. -Amyloid is a
principal compo-nent of the senile plaques that accumulate in the
brains of AD patients, and exercise has also been shown to
amelio-rate the accumulation of the phosphorylated form of the
protein, which is essential for the formation of neurofi-brillary
tangles. In addition, physical activity appears to promote
mechanisms of neuronal resilience that reduce inflammation in the
CNS [36] . Previous studies have shown that regular participation
in a physical activity, such as strength training, aerobics or
walking, strength, flexibility, balance and aerobic train-ing, or a
combination of these exercises for 16 weeks or 1 year is able to
improve some parameters related to health [5] . The quality of life
in AD patients can be improved by increasing their strength and
balance, thus reducing their risk of falling and increasing the
facility with which they are able to perform daily life activities
[5] . Becauseoftheimportancethatexerciseappearsto have in improving
the lives of AD patients, randomized controlled trials that
investigate the effects of exercise on
thesynthesisandreleaseofneurotrophicfactors,neu-rotransmitters,
hormones and other physiological
mark-ersarestillneeded,asarestudiesthatusemoreprecise methods of
measuring these effects. Parkinsons Disease PD is the second most
prevalent neurodegenerative dis-ease among elderly individuals, and
it generally affects men more often than it affects women [37] .
The disease is char-acterized by the loss of dopaminergic neurons
in the
sub-stantianigra,anditisassociatedwithdiminishedmito-chondrial
activity that results in an increased production ofreactive oxygen
species (ROS)[38] . The cardinal symp-toms of PD are hypokinesia,
tremors, postural imbalances
andgaitdeficits.Pathologicalsignsaremostcommon among individuals
who are between the ages of 50 and 60 [39] , but symptoms may
appear during a number of stages
oflife.Inadditiontotheaforementionedmotorimpair-ments, behavioral,
cognitive and other functional changes can be observed at different
stages of PD. Although drug treatment is the most widely used
method of treating PD, recent studies have shown that exercise and
pharmacologi-cal therapy are important interventions to improve
motor control,autonomyandawarenessofthepatientsday-to-day quality
of life[40] . In addition, individuals who have higher fitness
levels have a 33% lower risk (RR = 0.67) of developing PD [41] .
Participating in an exercise program that involves activities with
moderate-to-vigorous intensity during middle age appears to have a
neuroprotective effect of as high as 38% (RR = 0.62) for
individuals who are not affected by the disease[41] . Given the
relatively low cost of engaging an individual in a physical
training program and the various benefits that can be achieved by
doing so, exer-cise should be given special attention as a possible
means of protecting against or reducing the effects of this
disease. The evidence for the effectiveness of exercise in
ame-liorating the symptoms of PD has been favorable, but it remains
limited in scope. Both aerobic exercise (between 40 and 60% HRres,
34 times per week, 30 min per ses-sion) and strength training (23
times per week, 4080% of 1RM)appear to result in improved motor
function in PDpatients [42] ;thesetypesofexercisealsoappearto
improve the quality of life in individuals with PD [43, 44] .
However, strength training appears to be of greater ben-efit to
patients with the disease. Bloomer et al.[45] have assessed the
impact of an exercise program on the activi-ties of some oxidative
factors (C 3 H 4 O 2 and H 2 O 2 ). Indi-viduals engaged in
resistance training twice per week for
aperiodof8weeks(3sets,58reps,untilmomentary muscular failure).
Although these authors did not iden-tify any significant
between-group differences in the
ac-tivitiesoftheantioxidantenzymesthatwereanalyzed, thegroup that
had engaged in resistance training showed
significant(1516%)reductionsintheserumlevelsof various biomarkers
of oxidative stress, whereas members of the control group showed
14% increases in the serum
levelsofthesemarkers.Importantly,thisreductionoc-curred after a
relatively short period of training (8 weeks) with a low frequency
(twice per week). This result suggests that the positive
physiological ef-fects of strength training are rapid and indicates
that there may be an optimal dose-response relationship. Moreover,
PDpatientswhoparticipatedinexerciseprogramsthat
includedbothhigh-intensitystrengthtraining(6080%
4RM)andbalancetrainingshowedimprovedabilities to
controlthestabilityoftheirbodiesandwereableto maintain the same
level of performance over a period of 1 month
aftertheconclusionoftheirtrainingprogram [46] . These findings
support the hypothesis that the effects of this type of training
program remain stable even after a Downloaded by: 198.143.56.33 -
6/22/2015 7:51:51 AM Neuroscience of ExerciseNeuropsychobiology
2013;68:114DOI: 10.1159/0003509465period during which a PD patient
does not participate in
regulartraining.Theseimprovementsmayberelatedto neurobiological
changes that occur as a result of physical exercise, particularly
neurogenesis[47] , an increase in mi-tochondrial activity and an
increase in the synthesis of cer-tain neurotransmitters, such as
dopamine[48] . The neu-robiological mechanisms of the effects of
exercise are dis-cussed in detail in the Neurobiology of Exercise
section. Currently,thereareseveralpracticalconsiderations that must
be considered when determining the appropri-ate exercise regimen
for PD patients. Data from the recent literature recommend aerobic
activities using a cycle er-gometer and body support that are
performed 35 times perweekatalevelofintensity(low,moderateorhigh)
determinedonthebasisofthetrainabilityanddisease stage of each
patient. The levels of intensity are character-ized as follows: an
intensity
