Aging Brain

Question 1

Aging brain

Topological changes
General reasons for changes

Answer 1

Narrowed gyri, widened sulci
Dilated ventricles
Widened SA space

Due to:

• Loss/atrophy of neurons (low/no proliferative capacity)
• Regression of dendritic tree and reduction in spines (loss of input)
• Loss of myelin

All lead to mild/moderate memory impairments COMMON with normal aging

Question 2

What specific type of neurons are most impacted by normal neuronal atrophy/loss?

Why?

Answer 2

LARGE pyramidal neurons –> huge energy requirements due to large dendritic trees/cell bodies

Question 3

How does the amplitude of excitatory input change with age?

Answer 3

Amplitude does NOT really change–rather the NUMBER of inputs (decreased dendritic spine density).

Quantity is affected but not necessarily quality!

Question 4

Why are dopaminergic neurons in SNc vulnerable?

Answer 4

1) DOPAMINE oxidizable to superoxide.
2) NEUROMELANIN (that gives SN pigmentation) can sequester iron and generate free radicals.
3) Mitochondrial DNA deletions HIGHEST.
4) Local microglial reaction.

Question 5

Where is loss of myelin most prominent and how does this affect neurological activity?

Answer 5

Prefrontal and temporal cortex –> affect executive function, encoding/storing memory

GENU of cortex callosum usually more impacted than splenium.

Question 6

Where are sources of reactive oxygen species?

Answer 6

Leakage from normal mitochondrial respiration.
Synthesis from phagocytic cells to fight infections.
Dopamine degradation.

Question 7

How do microglia change with age?

Answer 7

Normally, at a younger age microglia can toggle because a “surveillance” state, where they have long processes to sample the environment and small cell bodies, and when needed go into an “activated” state, where they have reduce processes and enlarge cell bodies to produce cytokines/ROS.

With age, however, it becomes more difficult for microglia to return to their surveillance state and when activated can cause neurotoxic inflammation with increased ROS and cytokine production (“super-activated”).

Question 8

Lifestyle changes to help “slow” down damage to aging brain?

Answer 8

1) Mediterranean diet with low intake of dairy, meat, saturated FA, ETOH. Controversial whether caloric restriction helps.
2) Exercise
3) Make new synapses–use it or lose it!