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

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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
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The Hippocampus
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The Hippocampus
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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

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The Hippocampus

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

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Hippocampal Based Learning
Morris Water Maze
Carpenter Escape Paradigm
Voluntary exercise and environmental enrichment
improve this performance
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Enriched Environment
Running Wheel
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Increased Spatial Memory
Faster and more learning in runners
Van Praag et al. 1999b
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Increased Hippocampal Neurogenesis
Day 28
Day 1
more cell proliferation
Similar cell survival
Van Praag et al. 1999b
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Exercise and Enrichment Effects on DG Cells
of new cells that become neurons at Day28
New Cells Day28/Day1
More cell survival
neurogenesis
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Glutamate Receptors
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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.
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Exercise and the Synapse
Exercise enhances LTP
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Neuroanatomical Effects of Exercise
Cortical growth and restructuring Increases
metabolic capacity of the motor cortex
Anderson et al 2002
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Voluntary Exercise and Gestational Disruption
ALCOHOL!
Christie et al. 2005
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Brain Electrical Activity Associated with Exercise

• Electric brain current stimulates neurogenesis in
  the hippocampus
• Could be direct, via glutamate receptors
• indirect, via neurotrophin release

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Exercise induced changes in blood flow
also, increased permeability of the BBB and
glucose utilization by the brain
Increased blood flow to brain increased
nutrients and neurotrophic factors
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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
• IGF1 (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?

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B-endorphins
Released with the splicing of propiomelanocortin
preprohormone for ACTH b-endorphin a-MSH acti
on of b-endorphin can directly increase DG
neurogenesis via opiate receptor stimulation
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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
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Exercise Effects on Intracellular Mechanics
Activation of the IP3 and MAPK pathways via
neurotrophins Activation of CREB downstream of
cAMP
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Exercise Effects on Intracellular Mechanics
Activation of the IP3 and MAPK pathways via
neurotrophins Activation of CREB downstream of
cAMP
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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