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  1. This resource has been adapted from the webinar Exercise in Brain Health and Disease, which took place April 28, 2022. Watch the full recording on Neuronline. Q: I am very curious about exercise in children (as it was mentioned in the intro). Is there a correlation in (lack of) exercise in children and ADHD diagnoses (after controlling for pediatric healthcare access)? A by Aine Kelly: I am not aware that any such correlation exists, but there are studies that indicate exercise is helpful in managing ADHD symptoms in a school environment, eg https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787573/ Q: Are these studies limited to cardiovascular, aerobic exercise or have their been studies linking memory/learning changes to overall muscle mass or strength training? A by Henriette van Praag: The studies have been mainly focused on aerobic exercise which shows beneficial effects for brain function in humans and in animal studies. There are recent human and rodent studies pertaining to effects of strength training: https://pubmed.ncbi.nlm.nih.gov/34267577/ https://pubmed.ncbi.nlm.nih.gov/33547753/ https://pubmed.ncbi.nlm.nih.gov/34737021/ https://pubmed.ncbi.nlm.nih.gov/34003711/ https://pubmed.ncbi.nlm.nih.gov/33716112/ https://pubmed.ncbi.nlm.nih.gov/33279659/ https://pubmed.ncbi.nlm.nih.gov/34941437/ Q: Is possible to measure CTSB in samples of human saliva? A: by Henriette van Praag :Yes that is possible. https://pubmed.ncbi.nlm.nih.gov/35260133/ Q: Does CTSB correlate with the amount of distance run/activity? A by Henriette van Praag: Thank you. We have not measured this. Q: Running may not be a physical option for many older adults. Thus what is the threshold for activity that induces these changes. It muscle micro-injury a key requirement? A by Henriette van Praag: Older adults may be able to participate in other aerobic activities such as swimming or bicycling. It is not known if muscle micro-injury is a key requirement. Studies have focused on measures of cardio-respiratory fitness, heart-rate variability, cerebral vascular responses. https://pubmed.ncbi.nlm.nih.gov/30777641/ https://pubmed.ncbi.nlm.nih.gov/34337405/ https://pubmed.ncbi.nlm.nih.gov/35446599/ Q: What is the best evidence to indicate that exercise-induced new neurons are functionally integrated into the hipp circuit and they are indeed responsible for cognitive improvement? A by Henriette van Praag: There is evidence that new neurons are functionally integrated and relevant to cognition under basal and exercise conditions using a variety of approaches: https://pubmed.ncbi.nlm.nih.gov/11875571/ https://pubmed.ncbi.nlm.nih.gov/26589333/ https://pubmed.ncbi.nlm.nih.gov/32755589/ https://pubmed.ncbi.nlm.nih.gov/18664375/ https://pubmed.ncbi.nlm.nih.gov/29765836/ https://pubmed.ncbi.nlm.nih.gov/12941447/ https://pubmed.ncbi.nlm.nih.gov/18701066/ Q: How this exercise-induced CTSB increase can be explain with the fact that CTSB implicate in cause of amyloid accumulation? A by Henriette van Praag: There is controversy with regard to the role of CTSB in Alzheimer’s Disease. Some studies report increased pathology https://pubmed.ncbi.nlm.nih.gov/32305689/, whereas others show anti-amyloidogenic effects https://pubmed.ncbi.nlm.nih.gov/16982417/ https://pubmed.ncbi.nlm.nih.gov/27966067/ https://pubmed.ncbi.nlm.nih.gov/28797057/ There are also effects on synapse formation: https://pubmed.ncbi.nlm.nih.gov/31072786/ https://pubmed.ncbi.nlm.nih.gov/27989455/ Our research indicates that secreted, extracellular CTSB increase benefits brain function. Q: Question for Aine Kelly- does voluntary and involuntary exercise in mice contribute to changes in results? Thank you! A by Aine Kelly: In these studies we have used treadmill running, which is considered involuntary as the mice have no control over the speed or duration of exercise. There is an area at the rear of the treadmill where they can rest if they wish, and there is no inducement (eg shock or reward) used, however we have found that when mice are well habituated to the treadmill, they run for the entirety of the exercise session. Q: Could the traffic of immune cells and fluids through the brain during exercise could be involved in its benefits? A by Aine Kelly: This is a likely hypothesis - we haven't assessed blood flow or the glymphatic system in our experiments and we plan to look at blood flow in the next series of experiments. Q: Question for Aine Kelly. Did you check inflammation markers changes on protein level in early exercise model, or the exercise-induced changes were observed only on mRNA expression level? A by Aine Kelly: Because of the low tissue yield from the mouse brain, most of the markers were assessed at mRNA level. We did some immunohistochemistry to look at protein expression of GFAP and Iba1. These experiments are being written up for publication and hopefully the paper will be out before the end of the year. Q: What about construct validity of these exercise studies? Mice are raised in impoverished housing & then the EX groups get unlimited access to running wheels. Would housing in enriched environments (controls & EX groups) reduce or block benefits of exercise? A by Henriette van Praag: We have made a comparison between controls, exercise, enrichment, and enrichment plus exercise. Neurogenesis is only enhanced if there is access to running wheels: https://pubmed.ncbi.nlm.nih.gov/21878528/ A by Aine Kelly: The sedentary mice got the same handling as the EX mice and were placed on stationary treadmills for the same timeframe that the EX mice were exercising on the moving treadmill, so we believe we have controlled for any enrichment effects. Q: Question for Aine Kelly. Were rodents group- or single-housed in the early to mid-life exercise experiment? A by Aine Kelly: They were group housed and the treadmills have clear perspex dividers between lanes so they were exercising in the presence of other mice. Q: Was the exercise social i.e. play or done in isolation. It matters! A by Aine Kelly: I agree this matters! Mice were group housed and the treadmills have clear perspex dividers between lanes so they were exercising in the presence of other mice. Q: Any specialt excercise recommendation for people on psychiatric drugs.? Q: What does RET stand for. I missed the explanation Q: The type exercise could contribute to having a better memory, in people with COVID? Q: Thank you David. Was there any difference in the ability or adherence to exercise between Apoe4 carriers versus non-Apoe4 carriers? Q: Thank you all for fantastic talks. I would like to acknowledge the idea I learnt today that some of the benefit of exercise to the brain originates from periphery. My question is, do you also believe that the negative impact of sedentary life to the brain could be originating from periphery especially with in aging. A by David Jimenez Pavon: From my point of view, yes. Sedentary behaviors affect to body composition, muscle mass and muscle functionality, thus it means biological markers, function and others could be affected A by Aine Kelly: Yes -sedentary behaviour seems to contribute to chronic inflammation in all tissues, and in the context of aging, contributes to inflammation that extends to the brain. Q: Is it good exercising Everyday? A by Aine Kelly: The guidelines of 150min per week, or 30 min on 5 days each week, are a minimum. We should aim to do more than this, and moderate intensity daily exercise is fine. However if you are exercising at vigorous intensity, scheduling in recovery days is recommended in order to avoid injury. Q: A significant amount of research link mastication to cognitive function suggesting that reduced mastication is associated with cognitive decline and improved mastication improve cognitive function...basically similar to the effects of exercise. Do you have any knowledge and/or opinion of these studies? Thanks Q: I am also interested in the which type of excersice question. Are the cognitive benefits only seen for aerobic exercise? Thanks! A by Aine Kelly: Studies in both animal models and humans show that aerobic exercise is of most benefit. For general health through middle age and into older age, it is importance to include strength (resistance) exercise and exercise that maintains flexibility. Q: Thank you for the intresting talks.I have this question and will be intrested in your thoughts - Why the depression and other mental health problems in (young) athletes are so high ? Why we don’t see the benefits of exercisise in these population? Q: Do we see ‘better’ aging and functionality in aging ex-sport people? Are you aware of long-term studies measuring the effects of exercises in the younger age transfering to later life in aging athletes? A by Henriette van Praag: There is such evidence for masters athletes, see for example https://pubmed.ncbi.nlm.nih.gov/27445798/
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