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Restorative Benefit of Exercise on Affective Disorders. Affective Disorder Exercise BDNF 5-HT1A. Affective Disorders. D epression has a prevalence ranging from 5% to 20%
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Restorative Benefit of Exercise on Affective Disorders Affective Disorder Exercise BDNF 5-HT1A
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
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
Exercise ? Neurotrophins Serotonergic system Improvement Objectives Depressed patient
Methods • Animal model (Wistar rats): • Exercise • Antidepressant administration • Biochemical analysis • Local infusion of TrkB receptor blocker • Social defeat • Behavioral tests • Healthy volunteers: • Physical and psychological evaluation • Aerobic exercise • PET
0 week 3 weeks Exercise SSRI treatment Control Experimental Protocol • Animal model • WP1 • 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
0 week 3 weeks Exercise SSRI treatment Control Intrahippocampal TrkB blocker infusion Experimental Protocol • Animal model • WP2 • 5-HT1A receptor levels in the hippocampus in situ hybridization, IHC and autoradiographic ligand binding
0 week 1 week 2 weeks 3 weeks Socially Defeated Animal Model of depression Exercise SSRI treatment Control Experimental Protocol • WP3 • Animal model • Depressive-like behaviors sucrose preference test and Forced Swim Test • BDNF and 5-HT1A receptor levels in the hippocampus in situ hybridization, western blot, IHC and autoradiographic ligand binding
0 month 6 months 12 months ADIDAS Exercise ADIDAS Experimental Protocol • 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
Innovative Elements • Validation of an alternative, cost-effective therapeutic treatment for a major health and socioeconomic burden • The proposedresearch extends from an animal model (bench) to human subjects (proof of principle)
WP4 ELENI WP2 WP1 WP2 WP3 WP4 WP1 WP1 WP3 WP3 International Consortium Anima Sana in Corpore Sano