Environmental Enrichment and Voluntary Exercise Massively Increase Neurogenesis in the Adult Hippocampus via Dissociable Pathways. Andreas K. Olson, Brennan D. Eadie, Carl Ernst, and Brian R. Christie

The Hippocampus

In of the temporal lobe of the cortex Part of the limbic system (primitive emotion) Two primary division Dorsal- Memory and spatial navigation Ventral-anxiety (assoc w/amygdala) In Alzheimers- is damaged Memento

Hippocampus is associated with regulation of the HPA is involved with mood disorders The Hippocampus

Hippocampal Based Learning Morris Water Maze 15 min Carpenter Escape Paradigm Voluntary exercise and environmental enrichment improve this performance

Enriched Environment Running Wheel

Increased Spatial Memory Faster and more learning in runners Van Praag et al. 1999b

Increased Hippocampal Neurogenesis Day 1 Day 28 more cell proliferation Similar cell survival Van Praag et al. 1999b

Exercise and Enrichment Effects on DG Cells New Cells Day28/Day1 % of new cells that become neurons at Day28 neurogenesis More cell survival

Glutamate Receptors

Exercise and the Synapse Exercise enhances LTP involves synaptic molecules to include synapsin I, synaptotagmin, syntaxin. Increased levels of post-synaptic receptors, receptor mRNA, and other post-synaptic proteins Decreased levels of proteins that inhibit synapse formation.

Exercise and the Synapse Exercise enhances LTP

Neuroanatomical Effects of Exercise Cortical growth and restructuring Increases metabolic capacity of the motor cortex Anderson et al 2002

Voluntary Exercise and Gestational Disruption ALCOHOL! Christie et al. 2005

Brain Electrical Activity Associated with Exercise Electric brain current stimulates neurogenesis in the hippocampus Could be direct, via glutamate receptors indirect, via neurotrophin release

Exercise induced changes in blood flow Increased blood flow to brain = increased nutrients and neurotrophic factors also, increased permeability of the BBB and glucose utilization by the brain

Molecular Effects of Exercise Exercise increases levels of: BDNF (brain derived neurotrophic factor) promotes neurogenesis and neuron survival throughout life in brain only protects against hypoglycemia, ethanol and ischemia IGF 1 (insulin like growth factor) no neurogenesis without this co-application with FGF-2 (fibroblast growth factor) provides best results [also VEGF (vascular endothelial growth factor)] increase in blood supply?

B-endorphins Released with the splicing of propiomelanocortin preprohormone for ACTH  -endorphin  -MSH action of  -endorphin can directly increase DG neurogenesis via opiate receptor stimulation

Serotonin (5-HT) Stimulates neurogenesis Levels in the hippocampus are directly associated with neurogenesis Exercise increases TrpH activity 5-HT cells project to the hippocampus Trp (5-HT precursor) is elevated following exercise Does not influence hippocampal cell survival proliferation, not survival

Exercise Effects on Intracellular Mechanics Activation of the IP3 and MAPK pathways via neurotrophins Activation of CREB downstream of cAMP

Exercise Effects on Intracellular Mechanics Activation of the IP3 and MAPK pathways via neurotrophins Activation of CREB downstream of cAMP

Conclusions Exercise increases cell proliferation and survival in the hippocampus, and thus spatial memory This effect is multifactorial: Neurotrophic factors Neurotransmission Intracellular mechanics Changes in blood flow to the brain angiogenesis and increased BBB permeability