1. Restorative Benefit of Exercise on Affective Disorders Affective Disorder ExerciseBDNF5-HT1A

2. Affective 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

3. Exercise 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

4. Objectives Depressed patient Exercise Neurotrophins Serotonergic system ? Improvement

5. Methods Animal model (Wistar rats): Animal model (Wistar rats): Exercise Exercise Antidepressant administration Antidepressant administration Biochemical analysis Biochemical analysis Local infusion of TrkB receptor blocker Local infusion of TrkB receptor blocker Social defeat Social defeat Behavioral tests Behavioral tests Healthy volunteers: Healthy volunteers: Physical and psychological evaluation Physical and psychological evaluation Aerobic exercise Aerobic exercise PET PET

6. Experimental Protocol Animal model Animal model Exercise SSRI treatment Control WP1 0 week3 weeks BDNF levels in the hippocampus in situ hybridization and western blot 5-HT1A receptor levels in the hippocampus in situ hybridization, IHC and autoradiographic ligand binding

7. Experimental Protocol Animal model Animal model Exercise SSRI treatment Control WP2 0 week3 weeks 5-HT1A receptor levels in the hippocampus in situ hybridization, IHC and autoradiographic ligand binding Intrahippocampal TrkB blocker infusion

8. Experimental Protocol Animal model Animal model Exercise SSRI treatment Control WP3 Depressive-like behaviors sucrose preference test and Forced Swim Test 0 week3 weeks1 week2 weeks Socially Defeated Animal Model of depression BDNF and 5-HT1A receptor levels in the hippocampus in situ hybridization, western blot, IHC and autoradiographic ligand binding

9. Experimental Protocol Healthy Volunteers Healthy Volunteers WP4 Physical and Psychological evaluation Quality of life questionnaires: Beck Depression Inventory, Zung Self-rating Depression Scale 5-HT1A receptor levels in the brain PET using [11C]WAY-100635 0 month12 months6 months Exercise ADIDAS ADIDAS

10. Innovative Elements Validation of an alternative, cost- effective therapeutic treatment for a major health and socioeconomic burden Validation of an alternative, cost- effective therapeutic treatment for a major health and socioeconomic burden The proposed research extends from an animal model (bench) to human subjects (proof of principle) The proposed research extends from an animal model (bench) to human subjects (proof of principle)

11. International Consortium Anima Sana in Corpore Sano WP4WP4 WP3WP3 WP3 WP1WP1WP1 WP2 ELENI WP2