1. Physical Activity Enhances Brain Function

2. Cognitive Physiology In science, cognition refers to mental processes. These processes include attention, remembering, producing and understanding language, solving problems, and making decisions Cognitive physiology is the study of the underlying mechanisms of human thought

3. Physical Activity and Cognition Numerous studies have shown that adequate physical activities improve cognition in mice (Cotman CW, Berchtold NC, Christie LA., 2007) and human (Benjamin A. Sibley, Jennifer L. 2010; EtnierLautenschlager, Nicola T; Almeida, Osvaldo, p, 2006)

4. Hippocampus of Brain The hippocampus is located in the medial temporal lobe of the brain. Lateral view of the human brain, the frontal lobe is at left, the occipital lobe at right, and the temporal and parietal lobes have largely been removed to reveal the hippocampus underneath

5. Anatomy of human brain

6. Structure of Hippocampus

7. The hippocampus is a major component of the brains of humans and other vertebrates. The hippocampus is closely associated with the cerebral cortex, and in primates is located in the medial temporal lobe, underneath the cortical surface. It contains two main interlocking parts: Ammon's horn and the dentate gyrus.

8. Structure of Hippocampus

9. Function of Hippocampus It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in each side of the brain.

10. Nerve cells

11. Basic Structure of a Chemical Synapse

12. Neurotransmitters and Synaptic Transmission Excitatory postsynaptic potentials (EPSP) –Causes depolarization Inhibitory postsynaptic potentials (IPSP) –Causes hyperpolarization

13. Neurogenesis New neurons are continually born throughout adulthood in predominantly two regions of the brain: –The subventricular zone (SVZ) lining the lateral ventricles, where neural stem cells and progenitor generate new neurons (Neuroblast) that migrate to the olfactory bulb via the rostral migratory stream –The subgranular zone (SGZ), part of the dentate gyrus of hippocampus. Many of the newborn cells die shortly after they are born, but a number of them become functionally integrated into the surrounding brain tissue.

14. BrdU (dyed in red), a marker of DNA replication, highlights neurogenesis in the subgranular zone of hippocampal dentate gyrus. Fragment of an illustration from Faiz et al., 2005.

15. Neurogenesis and Cognition Recent experimental evidence supports the role of Brain-Derived Neurotrophic Factor (BDNF) in memory processes Memory acquisition and consolidation are associated with an increase in BDNF mRNA expression and the activation of its receptor: neurotrophic tyrosine kinase, receptor, type 2 (TrkB; a protein that is encoded by neurotrophic tyrosine kinase receptor 2 ( NTRK2) gene has been localized to a region on chromosome 9q22-q23 in humans ) Memory acquisition and consolidation are associated with an increase in BDNF mRNA expression and the activation of its receptor: neurotrophic tyrosine kinase, receptor, type 2 (TrkB; a protein that is encoded by neurotrophic tyrosine kinase receptor 2 ( NTRK2) gene has been localized to a region on chromosome 9q22-q23 in humans ) Yamada K, Nabeshima T. J. Pharmacol. Sci. (2003)

16. Brain-Derived Neurotrophic Factor Known as BDNF, is a protein that, in humans, is encoded by the BDNF gene. BDNF is a member of the "neurotrophin" family In the brain, it is active in the hippocampus, cortex, and basal forebrain—areas vital to learning, memory, and higher thinking. BDNF is important for long- term memory.

17. Physical Activity and Brain Structure and Function Scientists have shown that physical activity in the form of voluntary exercise results in an increase in the number of newborn neurons in the hippocampus of aging mice. The same study demonstrates an enhancement in learning of the "runner" (physically active) mice

18. Animal model

20. Results of the study The results show that cell proliferation was only increased in mice housed with unrestricted access to a running wheel (runners). voluntary physical activity and enrichment roughly doubled the total number of surviving new-born cells in the dentate gyrus. In contrast, mice trained in the water maze and yoked- swim controls showed no change the cell number, suggesting that this type of learning or activity alone is not an adequate stimulus for adult hippocampal neurogenesis What is the implication of this study to you !!

21. Animal Model (II)

22. Results of the study

24. Summary Mice who exercised performed better on a spatial learning task (finding their way through a water maze). Since the late 1990s, research (Cotman and Berchtold 2002 and von Pragg 2008) has revealed that aerobic exercise boosts levels of brain-derived neurotrophic factor (BDNF), a substance essential for the growth of brain cells Mobilizes the expression of genes that are believed to enhance brain plasticity—i.e., the ability of the brain to change its neural pathways Prevents brain tissue loss in older adults Prevents brain tissue loss in older adults

25. Compared sedentary mice with mice that ran an average of 3 miles each night on a running wheel (van Pragg et al. 1999) the aerobically- challenged mice showed dramatic brain growth. And the hippocampus—-a brain region associated with learning and memory--was twice as large (van Pragg et al. 1999) the brain cells of the aerobic mouse could sustain longer bouts of “long-term potentiation,” the increased efficiency of communication between neurons that occurs after neurons fire.

26. Long-term potentiation (LTP) Is a long-lasting enhancement in signal transmission between two neurons that results from stimulating them synchronously. It is one of several phenomena underlying synaptic plasticity, the ability of chemical synapses to change their strength. As memories are thought to be encoded by modification of synaptic strength, LTP is widely considered one of the major cellular mechanisms that underlies learning and memory

27. Long-term potentiation (LTP) Recordings are made intracellularly from CA1 neurons of the hippocampus while stimulation is applied to the Schaffer collaterals of CA3 neurons. The amplitudes of the EPSPs in the CA1 neurons are shown in B. For a single stimulus, the amplitude of the EPSPs is plotted at 100%. When a train of stimuli is applied instead, the amplitude of the EPSPs augment to about 150%, whereas with 4 such trains the amplitude increases to 250%. Many people think that long-term potentiation is an example of Hebb’s rule at work and that it is the physiological basis of memory.

28. Mechanism of LTP Glutamine induces N-methyl- D-aspartate (NMDA) receptor to depolarize and remove Mg ++ (inhibits Ca ++ Glutamine induces N-methyl- D-aspartate (NMDA) receptor to depolarize and remove Mg ++ (inhibits Ca ++ binding) Ca ++ Ca ++ then binds to NMDA receptor which increase a- amino-3-hydroxy-5-methyl-4- isoxa-zolep-propionate (AMPA) receptor number AMPA increases potentiated nerve impulse and generates LTP in CA1 of hippocampus Being suggests in associates with learning and memory

29. AMPA receptors AMPA receptors can move between an intracellular pool and the neuronal surface, by the processes of exocytosis and endocytosis AMPA receptors are also immobilized by increases in intracellular calcium levels, perhaps after calcium influx through postsynaptic calcium channels

31. Running animal and LTP

32. Glutamate

33. Neurovascular adaptations to exercise in the dentate gyrus of young adult mice associated with cognitive gain Clark PJ, Brzezinska WJ, Puchalski EK, Krone DA, Rhodes JS.2009

34. Neurovascular Adaptations Image shows the high density of blood vessels in the brain and the close proximity of brain cells to those vessels. A cut-away of one blood vessel shows vessel lining cells (endothelia-red).

35. Physical activity for Body and Brain Cotman CW, Berchtold NC, Christie LA. (2007) advocated that exercise increases synaptic plasticity by directly affecting synaptic structure and potentiating synaptic strength, and by strengthening the underlying systems that support plasticity including neurogenesis, metabolism and vascular function In addition, exercise reduces peripheral risk factors such as diabetes, hypertension and cardiovascular disease, which converge to cause brain dysfunction and neurodegeneration.

36. Human studies (I) Davis, C. L. (2011a) used sedentary, overweight 7- to 11-year-old children (N = 171, 56% girls, 61% Black, M ± SD age = 9.3 ± 1.0 years, body mass index [BMI] = 26 ± 4.6 kg/m², BMI z-score = 2.1 ± 0.4) whom were randomized to 13 ± 1.6 weeks of an exercise program (20 or 40 min/day), or a control condition. Dose-response benefits of exercise on executive function and mathematics achievement. Physical activity may prove to be a simple, important method of enhancing aspects of children's mental functioning that are central to cognitive development

37. Human study (II) Davis, C. L. (2011b) examined effects of aerobic exercise on overweight children's cognitive functioning Ninety-four sedentary, overweight but otherwise healthy children (mean age = 9.2 years, body mass index 85th percentile) were randomized to a low-dose (20 min/day exercise), high-dose (40 min/day exercise), or control condition. Exercise sessions met 5 days/week for 15 weeks. The Cognitive Assessment System (CAS), a standardized test of cognitive processes, was administered individually before and following intervention

38. Cont. Planning scores for the high-dose group were significantly greater than those of the control group. the effect of exercise seemed to depend on the dose. Kids enrolled in the 40- minute-a-day program made the biggest improvements – an average increase of 3.8 points in IQ. Kids in the 20- minute-a-day program made smaller gains.

39. PAAC promoted 90min/week of moderate to vigorous physically active academic lessons(3.0 to 6.0METS,~10 min each) delivered intermittently throughout the school day. Lessons were usually delivered in the classroom, but were also delivered in alternate school sites such as hallways and outdoors. PAAC=physical activity across curriculum

42. Exercise may prove to be a simple, yet important, method of enhancing aspects of children's mental functioning that are central to cognitive and social development 40 minutes a day of aerobic exercise improved executive function—-that aspect of intelligence that helps us pay attention, plan, and resist distractions (Davis et al 2007). 13 weeks of aerobic exercise was also linked with improved math skills and increased activity in the bilateral prefrontal cortex, a brain region associated with executive function (Davis et al 2011). Summary

43. Exercise for children is probably beneficial for the brain. Given that physical fitness is also good for the body Exercise should be fun. The mouse experiments are based on voluntary wheel-running. When rodents are forced to exercise, they don’t always reap the benefits aerobic exercise that your child really enjoys. Structured activities—-like team sports or dance lessons—-may be fine options. But so are nature walks, tree-climbing, roller-skating, and playing hide-and-seek.

44. Exercise improves brain function and reduces the risk of cognitive impairment associated with aging Regular exercise can protect the brain against: –Disease (Alzheimer’s) –Certain types of brain injury (stroke) How does exercise enhance brain health? –Enhances learning and memory –Stimulates formation of new neurons –Improves brain vascular function and blood flow –Attenuates mechanisms driving depression –Reduces peripheral factors for cognitive decline Inflammation, hypertension, and insulin resistance

45. Exercise Has Broad Positive Benefits on Brain Health

46. Discussion In your opinion, what is the most effective physical activity promote brain function for seniors. Why the role of Brain-Derived Neurotrophic Factor (BDNF) is important in memory processes. What do you do If you are going to implement a PAAC program in a junior high school class and may expect what kind of change as to brain function of the students.