Author:
Alan Woodruff

Key points

  • Exercise improves cognitive function in domains such as learning and executive function
  • At least in rodents, the beneficial effects of exercise are due mostly to neurogenesis
  • A range of chemicals are good candidates for how exercise promotes neurogenesis, many of which are circulating in the peripheral blood but which can cross the blood-brain barrier

Exercise is good for you. Nobody seems to think otherwise, yet for many of us it can still prove difficult to get outside for that run, ride or social game of soccer, even in the fantastic weather we’ve got here in Brisbane. I mean, if I lived in Montreal, I’d probably watch Netflix all day, comforted by popcorn, chocolate and maybe a warming glass of scotch… That’d be easy, but also a bad lifestyle choice. Not only does exercise improve your cardiovascular health, decreasing the risk of hypertension, diabetes, and stroke, but substantial evidence indicates that your brain benefits from exercise too, both in the short and long term. In the short-term, effects are mostly concerned with improved mood, but in the long-term, benefits have been demonstrated in terms of how well we (and mice) learn and how likely we are develop neurodegenerative disorders such as Alzheimer’s Disease (AD).

Exercise can help you learn, probably through neurogenesis

In the 1990s, the idea that the adult brain could produce freshly born neurons gained wide acceptance, overturning the dogma that the neurons you were born with were those you died with. This process, termed neurogenesis, doesn’t occur everywhere in the brain – in mice, newly born neurons in the adult are restricted to the hippocampus and the olfactory bulb; in humans, new neurons are found in the hippocampus and the striatum (a region important for motor planning and coordination, and also some aspects of cognitive tasks). Anyway, we’ll focus here on neurogenesis within the hippocampus, a memory-housing structure on which a lot of exercise-related research has focused.

Exercise, neurogenesis and learning in rodents

In the late 1990s, researchers found that mice living in an ‘enriched environment’ – with tunnels, mouse caves, running wheels and the like –  showed more new hippocampal neurons than mice who lived in a normal cage. People originally thought that the novelty of the items in the enriched environment was what caused the increase in neurogenesis, but we now know that the more important thing was that mice used the running wheels a lot – exercise causes neurogenesis.

Because the new neurons were found in the hippocampus, which is important for memory (particularly spatial memory in rodents), an obvious next step was to test whether the hippocampal neurogenesis caused by exercise could enhance memory. Most studies in rodents have indeed found that exercise improves spatial memory. Furthermore, blocking neurogenesis in mice that exercised prevented this improvement, indicating that the creation of new neurons by exercise was necessary for improving cognitive function. A host of research has backed up the links between exercise, neurogenesis and hippocampus-dependent learning in mice, but it’s important to point out that some studies have failed to find any connection, either between exercise and neurogenesis, neurogenesis and hippocampal learning, or exercise and learning. Science is rarely clear cut, and this is true for exercise, learning and neurogenesis in mice. Still, these failures to find an effect are in the minority, and may well be due to differences in the methods used: different exercise regimes, different ways of assessing neurogenesis, or different behavioural tasks.

The cognitive benefits of exercise in humans

OK, so it seems like we can make a mouse smarter just by giving it a running wheel. Does exercise have similar effects on us? The evidence for improved function, at least, is pretty unequivocal. A meta-analysis, meaning a combined analysis of multiple research papers, found that in healthy adults, exercise increased memory, attention, and executive function (this is the control of thinking – like planning things, reasoning, decision making). Positive effects have also been found in children, particularly for executive function, and in aged subjects, meaning that across the lifespan, human cognitive function is improved by exercise.

I should point out that the biological evidence for exercise-induced changes in the human brain is not as strong as the behavioural evidence. A lot of this may be because the tools we have to look at brain changes in the human aren’t suitable for assessing neurogenesis, at least not in people that are living. For example, conflicting results exist on whether exercise alters hippocampal volume; some say the volume increases, others say nothing happens. It’s entirely possible that neurogenesis is occurring and improving function, only the amount of neurogenesis isn’t large enough to change hippocampal volume enough that it can be reliably detected with MRI (magnetic resonance imaging) – our tools aren’t quite up to the task.

Aerobic exercise, such as running, has greater beneficial effects on your brain than strength or flexibility training.

Exercise protects against age-related cognitive decline

Neurodegeneration is the loss of neurons and synapses, and is a hallmark of Alzheimer’s Disease (AD) and other dementias. A number of mouse models of these disorders exist, and a common finding amongst the models is that in addition to losing neurons, the AD-like brain has a lower capacity for neurogenesis. If we can increase neurogenesis through something as straightforward as exercise, can we use exercise to combat age-related cognitive decline? It seems plausible. In aged mice, exercise does indeed both limit the usual decrease in neurogenesis and improve hippocampus-dependent learning. Running has also been reported to decrease the levels of amyloid beta (Aβ) plaques in the hippocampus of AD mice, one of the tell-tale markers of the AD brain. Furthermore, the decrease in Aβ correlated with improved spatial memory performance. These are promising results for the idea that exercise, through neurogenesis, can guard against neurodegeneration and age-related dementias, but once again it’s worth noting that not every single study has shown such effects of exercise on the AD-like mouse brain, although the majority have.

In humans, the evidence for decreased neurogenesis in AD is just a little more complicated. Surprisingly, it seems like more new cells are being produced, but these cells then have trouble turning into mature neurons that are integrated into circuits, possibly because of the presence of Aβ plaques. Functionally, the end result is a decrease in functional new neurons, just as in mouse models of AD. So there’s scope for exercise to increase neurogenesis back to normal levels in dementia patients, and we already know that this can have positive cognitive effects on learning and executive function. Does this actually play out? There actually isn’t a lot of evidence for or against this idea, although a meta-analysis has shown benefits of exercise on cognitive function in elderly patients with mild cognitive impairment, such as in AD. There is also some suggestion that mid-life exercise is more important for this effect than exercise at later stages of life; in other words, don’t leave it too late!

What is it about exercise that triggers neurogenesis?

Exercise increases a range of chemicals in the peripheral blood. Importantly, many of these substances are capable of crossing the blood-brain barrier and are known to enhance neurogenesis. It seems like what may be happening is that increased production of certain chemicals in peripheral blood leads to increased concentrations in the hippocampus, and that this can promote neurogenesis. We know that blood flow is increased during exercise, and it makes sense that chemicals in the blood that are upregulated during exercise are also responsible for effects within the brain. One well-established blood-borne mediator of exercise-induced neurogenesis is BDNF (brain-derived neurotrophic factor). In a way this wouldn’t be at all surprising to a neuroscientist; BDNF seems to be involved in just about everything in the brain.

Other endogenous chemicals (i.e. produced by the body) are also likely candidates for the effects of exercise on neurogenesis. Dr Daniel Blackmore, a postdoctoral researcher in the laboratory of Professor Perry Bartlett at QBI, has shown in mouse brain extracts that growth hormone (GH) is capable of promoting the production of precursor neurons, which later turn into mature neurons. GH is also increased by exercise and decreased in the aged brain, matching the profile of any sought after modulator of neurogenesis, at least regarding exercise. Dr Jana Vukovic of QBI has similar findings for another chemical, a so-called chemokine that is released by microglia, a type of immune cell for the nervous system. As with GH, this chemokine is upregulated by exercise and decreased in the aged brain, and promotes the production of precursor neurons in the hippocampus.

Summary

There is considerable research showing that exercise is good for your brain. It seems to improve memory and executive functions in people across the age spectrum, effects that, at least in mice, are due to the production of new neurons, particularly in the hippocampus. Through a similar mechanism, exercise also appears to be protective against the cognitive decline that is characteristic of dementias such as Alzheimer’s Disease. Add to these long-term cognitive benefits the known short-term effects of exercise on the brain, as well as the cardiovascular benefits, and you’ve got a pretty powerful modulator of our biology. So why wouldn’t you want to exercise? Because it’s hard work? Not good enough – it’s worth it.