Exercise and neurobiology James Robertson and Yufeng Zhang

Introduction Lifestyle need aerobic capacity aerobic physical activity (APA) generates and protects new neurons, increases the volume of brain improves cognition and reduce anxiety positive correlation between aerobic capacity and brain size across a wide range of mammals

Introduction Three times larger than expected for our body size. Major increase in brain size and brain size occurred during the early evolution of the genus Homo (Figure 1)

APA and brain brain size changes in human evolution are often interpreted in the context of cognition social complexity enhanced ecological demands on cognition at the same time as brain size began to increase, aerobic activity levels long-distance trekking

APA and brain Hypothesis: APA leads to neurogenesis human locomotor endurance had a measurable effect on the evolution of human brain structure and cognition APA leads to neurogenesis dentate gyrus of the hippocampus Gliogenesis frontal cortex

APA and growth factors Voluntary and forced running induce upregulation of BDNF Physical activity increase Insulin-like growth factor I Vascular endothelial growth factor (VEGF) BDNF, IGF-1 and VEGF all have important effects on metabolic pathways Growth factors in the periphery triggering neurogenic action

APA and growth factors two hypotheses for activity-induced adult neurogenesis: Neurotrophins and growth factors increased from endurance activity with ancillary effects on the brain links between activity and neurogenesis may create a neurogenic to enhance cognitive engagement during locomotor bouts

Physical activity and the evolution of brain growth

Correlation Intraspecific correlation Interspecific correlation BDNF IGF-1 VEGF Interspecific correlation MMR and brain size across mammals is likely to be related to differences in VEGF expression Do not clearly demonstrate evolutionary mechanisms

Figure 2. Relationships between body size, brain size and exercise capacity. Raichlen DA, Gordon AD (2011) Relationship between Exercise Capacity and Brain Size in Mammals. PLoS ONE 6(6): e20601. doi:10.1371/journal.pone.0020601 http://www.plosone.org/article/info:doi/10.1371/journal.pone.0020601

Artificial selection experiments Selected for high and low MMR in rats high levels of aerobic capacity both VEGF and IGF-1 Selective breeding for endurance running capacity affects cognitive but not motor learning in rats Selectively bred for high amounts of voluntary wheel-running higher BDNF levels larger mid-brain and dentate gyrus volumes

Human evolution Long hind-limbs

larger canal dimensions strongly associated with animals locomotor behaviours

Conclusion (i) intraspecific data linking aerobic capacity, brain size, neurotrophins and growth factors; (ii) interspecific data showing a relationship between aerobic capacity and brain size (iii) evolution experiments detailing how selection for aerobic performance alone can affect neurobiology

Raichlen 2012 – The Runners High Aerobic capacity linked to brain size, growth factors Problem: What happens if you don’t “need” to run? Goal-oriented behaviors with high energy costs Motivated by neurological rewards Conditions fitness enhancement Is there a reward-response from running?

Raichlen 2012 – The Runners High Endocannabinoids Released in activity-dependent manner Mesolimbic dopamine system eCBs relieve influence of inhibitory, GABAergic CB1 receptors eCBs activate dopamine (DA) neurons Sparling (2003) showed exercise AEA eCBs may not immediately impact anxiety system But, rewarding the exercise effort could select for beneficial traits Shown in other cursorial mammals

Raichlen 2012 – The Runners High 10 recreationally fit humans Could run for 30 min 8 mixed breed dogs Local mongrels 8 stupid ugly ferrets Minimal training (30 min running) Compared plasma AEA pre-post walk/run Stupid ferrets couldn’t walk on the treadmill Compared with stationary AEA

Raichlen 2012 – The Runners High Humans and Dogs Running increases plasma AEA Encourage aerobic exercise High intensity necessary Ferrets Jeez ferret, get off the couch sometime! Don’t you want to feel good?!?! Cursorial mammals rule!!!

Raichlen 2012 – The Runners High Running increases positive affect in humans

Heyman 2012 – eCBs, BDNF Does exercise influence anxiety via effects on neurogenesis? BDNF – neurotrophic factor critical for plasticity and neurogenesis Likely link between exercise and anti-depressive effect Previous studies in humans and animals are problematic Running wheel = novel environmental stimulation Human exercise not standardized for subjects

Heyman 2012 – eCBs, BDNF Study subjects: Homogenous group of male cyclists (n=11) Underwent exercise test to find standardized intensity – maximal power output (Wmax) 60 min at 55% Wmax 30 min at 75% Wmax (equivalent output condensed into time trial for intensity) Blood taken: 1- at rest; 2 – 60 min; 3 – immediately post-exercise; 4 – recovery Tested for: AEA, 2-AG AEA congeners OEA, PEA BDNF Beta endorphins cortisol

Heyman 2012 AEA and congeners increased during exercise and recovery 2-AG did not

Heyman 2012 Serum cortisol increased during exercise and recovery Positively correlated with AEA BDNF increased during exercise, fell during recovery Positively correlated with AEA at end of time trial, recovery Beta-endorphins only increased significantly during intense exercise

Heyman 2012 Rates of perceived exertion were not correlated with eCB levels RPE only correlated with Beta-endorphin during intense exercise

Heyman 2012 – eCBs, BDNF AEA and congeners definitely affect mood post-exercise Anti-depressant effect? What about the Beta-endorphins, could that be the runners high? Is it fair to point to BDNF as the method of influencing long term anxiety?

LETS GO OUTSIDE!!!!