Exercise Primes A Molecular Memory For Brain-Derived Neurotrophic Factor Protein

Induction In The Rat Hippocampus

N.C. Berchtold, et. Al.

BDNF

• Enhances synaptic transmission and neuronal excitability with upregulation of gene expression

• Modulates synaptic change such as LTP in the hippocampus– Deficiencies have shown to exhibit learning

deficits

• Essential survival factor and neuroprotectant

Impaired BDNF

• Factors in Alzheimer’s

• Mood and Eating disorders – Such as Depression

BDNF Benefits of Exercise

• Increased available BDNF for neuronal survival and resistance to brain insults

• Enhanced neurogenesis and LTP

• Increased resistance to Depression

• Lower risks of Alzheimer’s and dementia

• Allows for a lower threshold for theta-pattern stimulation for LTP

3 Questions of the Study

1. How do hippocampal BDNF protein levels respond to intermittent exercise?

2. Do BDNF protein levels remain elevated or decline rapidly to baseline?

3. How does a second exercise exposure regulate BDNF after levels have decayed to baseline?

Experiments

• Adult male Sprague-Dawley rats– 7 to 8 weeks old– 150 to 200 grams

• Food and water ad libitum

• 12 hr light/dark cycle

Levels of BDNF

• Either continuous daily access to running wheel and terminally sampled at 2, 4, 7, 14, 28, or 90 days.

Levels of BDNF

• Or intermittent access on alternating days of 7, 14, 21, or 28 days.

Stability of elevated BDNF

• 4 weeks of running, wheel locked and sampled at 0, 1, 3, 7, and 14 days.

Reintroduction of BDNF

• Determining if BDNF levels are related to absolute number of running days

• 14 days of priming run– continuous– intermittent

• 1 or 2 week of rest• A second test exercise of 2 days of running

Reintroduction of BDNF

• 2 weeks of daily running with either 1 week of rest

• Or 2 weeks of rest

Reintroduction of BDNF

• 4 weeks of intermittent running– 1 week of rest

– 2 weeks of rest

Results

BDNF daily vs. intermittent

• Continued to rise even for 90 days

222%

174%150%

BDNF daily vs. intermittent

• Similar increase, but slower rate

159%145%

124%

• BDNF has a time component that interacts with the exercise stimulus

• Intermittent training is ultimately as effective as daily training to elevate BDNF

BDNF elevated

• BDNF sampled at 0, 1, 3, 7, and 14 after 28 days of exercise

• BDNF sampled at 0, 3, and 7 days after 28 day period of alternating days of exercise

BDNF elevated

• Gradually declines, but slight rise at 7 days

151%128%

133%

BDNF elevated

• Levels no longer significant after 3 days

160%

BDNF “Memory”

• Daily runners– Sedentary

– 2 days of running

– 14 days of running

– 14 days of running with 7 days rest

– 14 days of running with 7 days rest + 2 days running

– 14 days running with 14 days rest

– 14 days running with 14 days rest + 2 days running

BDNF “Memory”

• Test run stimulates higher levels of BDNF

BDNF “Memory”

• Test run stimulates higher level, but takes longer to reach

Discussion

1. Intermittent exercise as effective as daily exercise to increase BDNF

• Progressively increase with longer running duration

• Induction of BDNF has time component that interacts with exercise stimulus

Paul A. Adlard Article

Significant increase in running at 4 weeks

Paul A. Adlard Article

• Shows that BDNF levels closely linked to level of activity as increases over 28 days

Discussion

2. BDNF levels remain elevated for several days

• Absolute amount of running days is important in regulating rate of decline

Discussion

3. BDNF is rapidly reinduced by brief exercise exposure, creating “molecular memory”

• May increase the conversion of precursor to BDNF or,

• May increase pool of available BDNF precursor

Jay’s Question’s

• Is the length or duration of each daily session have an effect on levels?

• Does the intensity of exercise during the session have an effect?