Restorative Benefit Restorative Benefit

of Exercise on of Exercise on Affective DisordersAffective Disorders

Affective DisorderAffective DisorderExerciseExerciseBDNFBDNF

5-HT1A5-HT1A

Affective DisordersAffective Disorders

Depression has a prevalence ranging from 5% to 20%

Current drug treatments are costly, only partly effective and present side-effects limit their therapeutic potential

ExerciseExercise

Exercise increases BDNF in the hippocampus BDNF influences serotonergic system Serotonergic system is intimately linked to depression 5-HT1A receptors are reduced in depressed patients

ObjectivesObjectivesDepressed patientDepressed patient

ExerciseExercise

NeurotrophinsNeurotrophins Serotonergic systemSerotonergic system ??

ImprovementImprovement

MethodsMethods Animal model (Wistar Animal model (Wistar

rats): rats): ExerciseExercise Antidepressant Antidepressant

administrationadministration Biochemical analysis Biochemical analysis Local infusion of TrkB Local infusion of TrkB

receptor blockerreceptor blocker Social defeatSocial defeat Behavioral testsBehavioral tests

Healthy volunteers:Healthy volunteers: Physical and psychological Physical and psychological

evaluationevaluation Aerobic exercise Aerobic exercise PET PET

Experimental ProtocolExperimental Protocol Animal modelAnimal model

Exercise SSRI

treatmentControl

WP1

0 week 3 weeks

BDNF levels in the hippocampusin situ hybridization and western blot

5-HT1A receptor levels in the hippocampusin situ hybridization, IHC and autoradiographic ligand binding

Experimental ProtocolExperimental Protocol Animal modelAnimal model

Exercise SSRI

treatmentControl

WP2

0 week 3 weeks

5-HT1A receptor levels in the hippocampusin situ hybridization, IHC and autoradiographic ligand binding

Intrahippocampal TrkB blocker infusion

Experimental ProtocolExperimental Protocol Animal modelAnimal model

Exercise SSRI

treatmentControl

WP3

Depressive-like behaviorssucrose preference test and Forced Swim Test

0 week 3 weeks1 week 2 weeks

Socially Defeated AnimalModel of depression

BDNF and 5-HT1A receptor levels in the hippocampusin situ hybridization, western blot, IHC and autoradiographic ligand binding

Experimental ProtocolExperimental Protocol Healthy VolunteersHealthy Volunteers

WP4

Physical and Psychological evaluationQuality of life questionnaires: Beck Depression Inventory, Zung Self-rating Depression Scale

5-HT1A receptor levels in the brainPET using [11C]WAY-100635

0 month 12 months6 months

Exercise ADIDASADIDAS

ADIDASADIDAS

Innovative Elements Innovative Elements

Validation of an alternative, cost-Validation of an alternative, cost-

effective therapeutic treatment effective therapeutic treatment

for a major health and for a major health and

socioeconomic burdensocioeconomic burden The proposedThe proposed research extends research extends

from an animal model (from an animal model (benchbench) to ) to

human subjects (human subjects (proof of proof of

principleprinciple))

International Consortium International Consortium

Anima Sana in Corpore Anima Sana in Corpore Sano Sano

WP4WP4

WP4WP4

WP3WP3WP3WP3WP3WP3WP1WP1WP1WP1

WP1WP1WP2WP2

ELENI ELENI WP2WP2