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How exercise improves memory

by System Administrator / Friday, 1 July 2016 /

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How exercise improves memory
The hippocampus in the brain switches to fat as an energy source after glucose is depleted from exercise), leading to release of BDNF, associated with cognitive improvement. Researchers have found out how.
June 24, 2016

Experimental design (partial view). Study participants learned 90 picture-location associations over a period of approximately 40 minutes before being randomly assigned to one of three groups: one group performed exercise immediately, the second performed exercise four hours later, and the third did not perform any exercise. Forty-eight hours later, participants returned for a test to show how much they remembered while their brains were imaged via magnetic resonance imaging (MRI).

Physical exercise after learning improves memory and memory traces if the exercise is done four hours later, and not immediately after learning, according to findings recently reported (open-access) in the Cell Press journal Current Biology.

It’s not yet clear exactly how or why delayed exercise has this effect on memory. However, earlier studies of laboratory animals suggest that naturally occurring chemical compounds in the body known as catecholamines, including dopamine and norepinephrine, can improve memory consolidation, say the researchers at the Donders Institute at the Radboud University Medical Center in the Netherlands. One way to boost catecholamines is through physical exercise.

The researchers tested the effects of a single session of physical exercise after learning on memory consolidation and long-term memory. Seventy-two study participants learned 90 picture-location associations over a period of approximately 40 minutes before being randomly assigned to one of three groups: one group performed exercise immediately, the second performed exercise four hours later, and the third did not perform any exercise. The exercise consisted of 35 minutes of interval training on an exercise bike at an intensity of up to 80 percent of participants’ maximum heart rates. Forty-eight hours later, participants returned for a test to show how much they remembered while their brains were imaged via magnetic resonance imaging (MRI). The researchers found that those who exercised four hours after their learning session retained the information better two days later than those who exercised either immediately or not at all.

The researchers plan to follow up with another study of the timing and molecular underpinnings of exercise and its influence on learning and memory in more detail.

The researchers were supported by a grant from the European Research Council.

Brain chemicals

Exercise induces synthesis of a chemical called DBHB in the liver. In the hippocampus, DBHB induces Bdnf gene expression, which in turn has positive effects on memory, cognition and synaptic transmission. (credit: Sama F. Sleiman et al./eLife)

In a related study published in eLife June 2 with mice, researchers note that exercise is known to be accompanied by an increase in brain-derived neurotrophic factor (BDNF) in the hippocampus, which is associated with cognitive improvement and the alleviation of depression and anxiety.

But how? It is known that a substance known as β-hydroxybutyrate (DBHB), produced in the liver from fatty acids, serves as an alternative energy source when glucose (blood sugar) levels are reduced. In their research (with mice on a running wheel for 30 days vs. no exercise), they found that the resulting increase of DBHB blocked the action of histone enzymes, which normally inhibit the production of BDNF.

Confirming that, injecting DBHB directly into the brains of mice also led to increase in BDNF.

Abstract of Physical Exercise Performed Four Hours after Learning Improves Memory Retention and Increases Hippocampal Pattern Similarity during Retrieval

Persistent long-term memory depends on successful stabilization and integration of new memories after initial encoding [ 1, 2 ]. This consolidation process is thought to require neuromodulatory factors such as dopamine, noradrenaline, and brain-derived neurotrophic factor [ 3–7 ]. Without the release of such factors around the time of encoding, memories will decay rapidly [ 3, 5, 6, 8 ]. Recent studies have shown that physical exercise acutely stimulates the release of several consolidation-promoting factors in humans [ 9–14 ], raising the question of whether physical exercise can be used to improve memory retention [ 15–17 ]. Here, we used a single session of physical exercise after learning to exogenously boost memory consolidation and thus long-term memory. Three groups of randomly assigned participants first encoded a set of picture-location associations. Afterward, one group performed exercise immediately, one 4 hr later, and the third did not perform any exercise. Participants otherwise underwent exactly the same procedures to control for potential experimental confounds. Forty-eight hours later, participants returned for a cued-recall test in a magnetic resonance scanner. With this design, we could investigate the impact of acute exercise on memory consolidation and retrieval-related neural processing. We found that performing exercise 4 hr, but not immediately, after encoding improved the retention of picture-location associations compared to the no-exercise control group. Moreover, performing exercise after a delay was associated with increased hippocampal pattern similarity for correct responses during delayed retrieval. Our results suggest that appropriately timed physical exercise can improve long-term memory and highlight the potential of exercise as an intervention in educational and clinical settings.

Abstract of Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body β-hydroxybutyrate

Exercise induces beneficial responses in the brain, which is accompanied by an increase in BDNF, a trophic factor associated with cognitive improvement and the alleviation of depression and anxiety. However, the exact mechanisms whereby physical exercise produces an induction in brain Bdnf gene expression are not well understood. While pharmacological doses of HDAC inhibitors exert positive effects on Bdnf gene transcription, the inhibitors represent small molecules that do not occur in vivo. Here, we report that an endogenous molecule released after exercise is capable of inducing key promoters of the Mus musculus Bdnf gene. The metabolite β-hydroxybutyrate, which increases after prolonged exercise, induces the activities of Bdnf promoters, particularly promoter I, which is activity-dependent. We have discovered that the action of β-hydroxybutyrate is specifically upon HDAC2 and HDAC3, which act upon selective Bdnf promoters. Moreover, the effects upon hippocampal Bdnfexpression were observed after direct ventricular application of β-hydroxybutyrate. Electrophysiological measurements indicate that β-hydroxybutyrate causes an increase in neurotransmitter release, which is dependent upon the TrkB receptor. These results reveal an endogenous mechanism to explain how physical exercise leads to the induction of BDNF.


References:

    van Dongen et al. "Physical Exercise Performed Four Hours after Learning Improves Memory Retention and Increases Hippocampal Pattern Similarity during Retrieval" http://www.cell.com/current-biology/fulltext/S0960-9822(16)30465-1. Current Biology. (open access)
    Sama F Sleiman et al. Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body β-hydroxybutyrate. eLife 2016;5:e15092 (open access)


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