Exercising Our Minds: Effects of Exercise on Brain Structure & Function

Transcription

1 Public Lecture Exercising Our Minds: Effects of Exercise on Brain Structure & Function Dr. Brian R. Christie Division of Medical Sciences, University of Victoria Cellular and Physiological Sciences, UBC The Brain Research Centre, UBC The Jack Brown and Family Alzheimer Research Foundation

2 Changes Time might change me, but I can t change time... Sir David Bowie How we think about the brain Some of the people that have shaped our view of the brain. How the effects of exercise on the brain is changing our view of it again.

3 We were taught the brain is like a computer. We re all obsolete models! =

4 Our brains are dynamic. Like skin and muscle, brains change in response to their environments

5 The Brain is composed of billions of interconnected cells Donald Hebb CONNECTIONISM Networks; Cells that fire together, wire together Neurons Glia Endothelial/ Vasculature Neural Stem Cells

6 Why Study the Hippocampus? Severe Epilepsy, bilateral initiation Performed bilateral medial temporal lobectomy. H.M. was 27 yrs old. Henry Gustav Molaison Died December 2, 2008 Spent 55 yrs in a state of permanent amnesia William Scoville, MD Sept 1, 1953 performed bilateral temporal lobe removal Brenda Milner, Ph.D. -Showed working and procedural memory intact. -Couldn t form new explicit memories.

7 The Hippocampus contains neural stem cells New Cells expressing GFP

8 Neurogenesis Dendrites in Molecular Layer Granule Cell Layer Mossy Fiber Projection to CA3 Neural Stem Cells Daughter Cells

9 Donald Hebb showed enriched environments improved learning and memory in rats. Kempermann and Gage showed enriched environments increased neurogenesis in the hippocampus.

10 EXPERIMENTAL DESIGN Assessing the effects of exercise. 1 Running Wheel 2 Water maze 3 Electrophysiology BRDU + Normal Cage Histology BRDU +

11 RESULTS Exercise Improves Water Maze Learning 1000 Control 800 Runner Path (cm) Latency (ms) * * * Time Per Quandrant (sec) Control * Runner Days van Praag et al., 1999

12 Neurogenesis can be enhanced Exercise increases hippocampal neurogenesis 2-3 times!

13 Neurogenesis in the adult human brain! Human Cells Rat Cells Eriksson et al Nat. Med 4(11):1313

14 Animals that exercise produce a lot of new cells And we can identify them and study them! New Cells expressing GFP

15 Exercise helps new cells grow and mature. New Cell Adolescent Cell Adult Cell

16 Exercise can also help the cells we already have!

17 Hebb s Postulate: Synaptic Plasticity LTP LTD TIME

18 EPSP (% Change) EPSP (% Change) RESULTS Exercise enhances LTP in the DG A 100 Runners Controls B STPS Time (minutes) 0-25 WTPS Time (minutes) van Praag et al. 1999, PNAS. 96(23): Farmer et al., 2004, Neuroscience.

19 Exercise increases the number of spines on neurons 02970fa2

20 Brian Christie, DMS, UVIC Exercise increases BDNF and NR2B receptor mrna Farmer et al., 2004

21 Summary 1. Exercise increases the production of new neurons in the brain. 2.Exercise enhances the growth of existing dendrites on neurons. 3.Exercise enhances the number of spines on neurons. 4.Exercise enhances synaptic plasticity 5.Exercise enhances learning and memory processes.

22 Brian Christie, DMS, UVIC Can we use what we know about the effects of exercise for therapeutic purposes in neurological disorders?

23 Brian Christie, DMS, UVIC Fetal Alcohol Syndrome Fetal Alcohol Syndrome (FAS) or Fetal Alcohol Spectrum Disorder (FASD) is caused by women drinking alcohol while pregnant. FAS generally refers to the spectrum of morphological and cognitive disorders that are apparent in the offspring of heavy drinkers. Many women don t even know they are pregnant for months after conception and continue to drink until they find out they are pregnant. Their children are probably more at risk for FASD than FAS. No amount of alcohol in pregnancy has been established as safe for the fetus. About 1% of North Americans suffer from FAS (Fetal Alcohol Syndrome) or FASD

24 Effects of Prenatal Ethanol Exposure are virtually the diametric opposite of those of exercise. Brian Christie, DMS, UVIC 1. There is cell loss in the Hippocampus of offspring following prenatal ethanol exposure. Dr. Joanne Weinberg 2. Hippocampal cells do not appear to be fully mature. 3. Animals (including humans) exposed to ethanol prenatal exhibit impaired learning. 4. It s harder to show electrophysiological indices of learning and memory (LTP) in animals following PNEE. Can exercise rescue animals from the deleterious effects of PNEE?

25 Brian Christie, DMS, UVIC These experiments require 3 groups of animals 1. Ad Libitum Controls (AL) 2. PNEE (35.5% ethanol derived calories) 3. Pair-fed (PF) get the same number of calories as PNEE animals but have maltose-dextrin substituted for ethanol. Ethanol Diet Pair-fed, No Ethanol Ad Libitum (no diet, no alcohol)

26 Brian Christie, DMS, UVIC Gestation Day 1 Female rats become pregnant and begin prenatal feeding (ethanol, pair-fed, or ad libitum diet). or 23 days Postnatal Day 1 Special diets end. Pups are born. Litters are culled to 10 (5 m and 5 f). 22 days Postnatal Day 22 Pups are weaned and housed individually in either normal cages or cages containing an exercise wheel according to sex and prenatal diet. Female Offspring Male Offspring The offspring Never drink themselves * Note this is the equivalent of drinking in G1 and G2 only.

27 Time Time in in seconds Time in seconds Time in seconds Brian Christie, DMS, UVIC Behavioural Testing in the offspring when they are adults (P50-60). Reference memory PNEE runner PF runner AL runner PNEE PF AL Working memory Trial 1 over 5 days PNEE (n=11) PF (n=13) AL (n=10) Trial 2 over 5 days Trial over days PNEE PF AL PNEE runner AL runner

28 EPSP Slope (% baseline) Brian Christie, DMS, UVIC Normal adult animals show more LTP when they are allowed to exercise. Ad Libitum Ad Lib Runners (n=7) Ad Lib Non-runner (n=4) Time (minutes)

29 EPSP Slope (% baseline) Brian Christie, DMS, UVIC Pair-fed animals also show more LTP when they are allowed to exercise. Pair-Fed PF-R (n=8) Pair-Fed-NR (n=8) Time (minutes)

30 EPSP Slope (% Baseline) Brian Christie, DMS, UVIC PNEE animals also show more LTP when they are allowed to exercise! PNEE PNEE-R (n=7) PNEE-NR (n=9) Time (min)

31 EPSP Slope (% baseline) Brian Christie, DMS, UVIC After exercising, PNEE animals do slightly better than normal non-exercising animals. Ad Libitum Ad Lib Runners (n=7) Ad Lib Non-runner (n=4) PNEE Runners (n=7)" PNEE Non-Runners (n=9)" Time (minutes)

32 # of BrdU cells/section BrdU Injection Cell Proliferation Brian Christie, DMS, UVIC Neurogenesis Runner Nonrunner Nonrunner DG Proliferation Hr 4 weeks 0 PNEE Pair-fed Ad-lib

33 Mean # BrdU cells/hpc Brian Christie, DMS, UVIC DG Neurogenesis VE Con * * * PNEE Pair-fed Ad-lib

34 Brian Christie, DMS, UVIC Take Home Messages 1. Exercise enhances neurogenesis in the DG. 2. Exercise enhances synaptic plasticity in the DG. 3. Exercise increases dendritic complexity in the DG. 4. Exercise enhances learning in behaviors that seem to involve the DG. 5. Early teratogen exposure can reduce neurogenesis, synaptic plasticity, and learning. 6. Exercise may help to alleviate these deficits.

35 PDF MD Brian Christie, DMS, UVIC MD PhD PhD MD MD MD Nursing hon PhD PDF MSc

36 The Ups and Downs of Neurogenesis Physical Activity Enriched Environments Anti-depressants Anti-Oxidant Rich Foods? Omega-3 Fatty Acids? Mental Exercise? Social Interactions? Inactivity Isolation Depression Brain Irradiation Alcoholism Drug use Stress Poor Sleep Working for the government