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Lecture Notes for Brain Aging
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Objectives:1. Global impact of brain aging
2. Concept of adult neurogenesis
3. Different locations of adult neural stem cells and their neurogenic niche in
mammalian brains
4. One example of molecular control of adult hippocampal neurogenesis
5. Possible functions of adult hippocampal neurogenesis
6. Impact of aging on hippocampal neurogenesis
7. Impact of environmental factors on hippocampal neurogenesis
GLOBAL IMPACT:
- 2050 = estimated population of 2 billion people 60+ years old
- 2050 = estimated 130 million people will have dementia
- Over 65 year old risk of dementia doubles every 5 years
- Dementia and cognitive decline are in a cycle with the fundamental mechanisms of
brain aging
- Fundamental mechanisms that age the brain cognitive decline
- Cognitive decline increases mechanisms that age the brain
- Genetics, education, occupation, environmental, health and available health care
impact the ways we age
- Interventions must prevent or delay cognitive aging + dementia
- Focus for intervention = targeted altered neurogenesis
- Can also look at vulnerabilities (diabetes, early-life stress, obesity etc.) and other
cellular mechanisms (inflammation, impaired DNA repair etc.) to aid intervention
ADULT NEUROGENESIS:
- Process where neurones are generated from neural stem cells in the adult brain
- Different to prenatal neurogenesis
- Was assumed that neurogenesis was not possible, until found evidence of postnatal
hippocampal neurogenesis in rats
- Limited to specific brain regions
o Subventricular zone of lateral ventricles
New neurones from this region project into olfactory bulb
Mostly evident in rodents (not humans) – likely because rodents rely
on the olfactory bulb much more heavily
o Subgranular zone of dentate gyrus (in hippocampus)
New neurones from this region project into the CA3 region
CA3 region of brain = role in memory processing + neurodegeneration
Demonstrated in rodents
- Neural stem cells in dentate gyrus proliferate, migrate + differentiate to have
projections that extend out of dentate gyrus
- Projections join + innervate CA3 region through mossy fibre pathway between
dentate gyrus and CA3
- CA3 neurones innervate CA1 neurones CA1 neurones innervate entorhinal cortex
entorhinal cortex innervates neocortical associated areas + dentate gyrus
o All confirmed in rodent studies
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