Aerobic exercise improves mental well being

Kirk Erikson talking
Kirk Erikson on Excersice and psychiatric disease
Excersice and psychiatric disease at ECNP
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Kirk Erikson on Excersice and psychiatric disease
Excersice and psychiatric disease at ECNP

Get on your running shoes if you want good mental health in later life – it’s never too late to start! Those were the messages coming from a highly informative and stimulating session entitled ‘Exercise and psychiatric disease: should patient take the challenge?’ that occurred during this year’s ECNP.  But maybe it’s not just patients who need to start taking regular anaerobic exercise – it’s all of us!

Where has the evidence supporting such claims emanated from? In the first part of the session Henriette van Praag, Maryland, USA, talked the audience through some of the exciting preclinical research that may help explain what’s happening.

Hippocampus – site of neurogenesis in adult

It has now been accepted that the hippocampus, an area critical for learning, is one site of neurogenesis present within the adult brain. Professor van Praag showed how, in animal models, running increases hippocampal neurogenesis and memory function.

Running enhances new neurogenesis and rewires neurocircuitry

In a series of elegant experiments in animals, it was shown that environmental enhancement, particularly running, enhanced new neurogenesis. Running also enhanced learning and performance of hippocampal-dependent tasks.  Closer inspection of the dentate gyrus, a region involved in pattern separation, also revealed that rats who were allowed to run in running wheels performed significantly better at intricate pattern separation tasks than sedentary animals. 

Such exercise expands entorhinal cortical input to new neurons that are involved with spatial and contextual memory. Thus, running rewires new neurocircuitry not solely in the hippocampus but also in the entorhinal cortex and the septum – all areas for learning and memory and those first affected by neurodegenerative diseases.

Muscling in on cognition

Intriguingly, the benefits of exercise for cognition appear to originate from muscle. A search for factors released into the circulation by muscle homed in on the candidate molecule cathepsin B (CTSB). In mice, running increased CTSB levels both in muscle and in plasma and enhanced spatial memory. In knock out CTSB mice, however, there no enhancement in the spatial memory compared to normal controls. This suggests, therefore, that CTSB, a substance released from the muscle, may be partly responsible for a cognitive effect occurring in the brain.

CTSB – mind-altering myokine

Furthermore, improved fitness in humans also correlated with increased plasma levels of CTSB and improved memory function in humans undergoing treadmill testing. Thus, the myokine, CTSB, is associated with memory function in both mice and humans.

Dr Kirk Erickson, Pittsburgh, USA, took the presentation one stage further by asking the provocative question – is memory decline inevitable with aging? In short, yes BUT there are things that can be done to decelerate the rate of decline.  And one of them is to exercise.

Less than 10% of us exercise sufficiently

Exercise has widespread effects on the brain and moderate intensity exercise several days a week is sufficient for improving brain health.  Unfortunately, compliance with exercising - trying to achieve 150 minutes aerobic exercise per week - in the adult population is poor. Less than 10% of us manage it.

It’s never too late

However, even after the age of 60 years, starting to exercise is not futile; even those who are sedentary can improve their cognitive function  - as well as their muscle strength and aerobic capacity, of course! Results of a recent meta-analysis suggest that fitness training can also have beneficial effects on human cognition, particularly on tasks requiring executive control processing.  

Dr Erickson and his team took this one step further and described the findings from a 1-year study into whether aerobic exercise could increase hippocampal volume and, therefore, improve cognitive function in human subjects.

Even after the age of 60 years, starting to exercise is beneficial

Study subjects were strictly monitored and parameters for improvement were objectively measured during a series of clinical visits that regularly occurred during the study.  A total of 120 patients were randomly assigned to moderate and aerobic exercise or to mild exercise training. The aerobic exercise training increased the volume of the anterior hippocampus by 2%, leading to improvements in special memory and reversed age-related loss in volume by 1-2 years, while in the control group hippocampal volume declined. Increased hippocampal volume was also associated with increased serum levels of BDNF.

Sweat to expand your hippocampus

Aerobic exercise appears to reverse hippocampal volume loss in adults and improves memory

Thus, aerobic exercise appears to reverse hippocampal volume loss in adults and improves memory – with potential long-term consequences for disease of the brain.

Symposium references
  1. Voss MW, Vivar C, Kramer AF, van Praag H. Bridging animal and human models of exercise-induced brain plasticity. Trends Cogn Sci. 2013 Oct;17(10):525-44.
  2. Vivar C, Peterson BD, van Praag H. Running rewires the neuronal network of adult-born dentate granule cells. Neuroimage. 2016 May 1;131:29-41. doi: 10.1016/j.neuroimage.2015.11.031. Epub 2015 Nov 14.
  3. Narkar VA, Downes M, Yu RT, Embler E, Wang YX, Banayo E, et al. AMPK and PPARdelta agonists are exercise mimetics. Cell. 2008 Aug 8;134(3):405-15.
  4. Kobilo T, Yuan C, van Praag H. Endurance factors improve hippocampal neurogenesis and spatial memory in mice. Learn Mem. 2011 Jan 18;18(2):103-7.
  5. Moon HY, Becke A, Berron D, Becker B, Sah N, Benoni G et al. Running-Induced Systemic Cathepsin B Secretion Is Associated with Memory Function. Cell Metab. 2016 Aug 9;24(2):332-40.
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