BRAIN REJUVENATION HOW TO KEEP BRAIN STEM CELLS HAPPY
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1 BRAIN REJUVENATION HOW TO KEEP BRAIN STEM CELLS HAPPY Natalia Surzenko, PhD Research Assistant Professor UNC Chapel Hill Nutrition Research Institute October 13, 2015
2 MY JOURNEY Tallinn, Estonia Aiken, SC Harvard Medical School UNC Chapel Hill
3 OUR GROUP Zeisel lab at the UNC NRI
4 TODAY S PRESENTATION What are stem cells? What are neural or brain stem cells? How do neural stem cells come about? What nutrients affect neural stem cells and brain regeneration? How do lifestyle factors affect neural stem cell properties?
5 THE HOPES FOR NEURAL STEM CELL RESEARCH Possible repair of the diseased brain and other regions of the nervous system Better understanding of disease pathology Better management of cognitive function during aging
6 WHAT IS A STEM CELL? A cell that can selfrenew or replicate itself A cell that can give rise to many other types of cells in the body Stem cells can be pluripotent, multipotent or unipotent
7 DIFFERENT GENES ARE ACTIVE IN STEM CELL VERSUS DIFFERENTIATED CELLS Example of fat cell genes Differentiation Pre-fat cells, or stem cells, don t express fat cell genes Stem cells express genes that prevent them from becoming differentiated or specialized University of Southern Denmark, Mandrup group Differentiating stem cells will switch on fat cell genes, and switch off stem cell genes
8 EMBRYONIC STEM CELLS Present in the early embryo Are pluripotent can produce many kinds of cell types Can be grown in a culture dish Can become other cell types
9 INDUCED PLURIPOTENT CELLS Robinton and Daley, Nature, 2012
10 MORE STEM CELL APPLICATIONS Skin stem cells can grow hair ips cells make heart muscle ips cells make brain cells Toyoshima et al, Nature Communications, 2012 Tim Kamp lab University of Wisconsin ReproCell
11 DIFFERENT TYPES OF ADULT STEM CELLS Adult stem cells can be found in different tissues Intestine Brain U.C.-Irvine Ramalingam et al, 2012
12 WHERE ARE THE ADULT NEURAL STEM CELLS LOCATED? Sanes and Lichtman labs National Institute of aging Hippocampus the learning and memory center
13 ADULT NEURAL STEM CELLS CAN Make new neurons Make new astrocytes = glial cells Make new oligodendrocytes = myelinating cells Enikolopov lab Cold Spring Harbor laboratory
14 MAIN CELL TYPES OF THE BRAIN: NEURONS, ASTROCYTES AND OLIGODENDROCYTES Neurons = can transform chemical signal into electrical stimulus and transmit information between each other
15 NEURONS ARE DIVERSE IN SHAPE AND FUNCTION Different brain regions contain different types of neurons: -Projection neurons can talk to cells located in other brain regions -Interneurons signal locally to regulate activity of other neurons Ramón y Cajal
16 GLIAL CELLS SUPPORT NEURONAL FUNCTION Astrocytes = provide nutrients, remove waste Oligodentrocytes = produce myelin and ensheathe neuronal axons Target Health Inc.
17 NEURAL STEM CELLS DURING DEVELOPMENT Cerebral cortex Neurons Glia Developing brain Adult stem cell
18 RADIAL GLIA ARE NEURAL PROGENITOR CELLS IN THE DEVELOPING BRAIN Radial glial cells can divide to self-renew Radial glia can divide assymmetrically to selfrenew and to produce a neuron They can divide to produce neural precursor cells. This type of cell division depletes neural stem cells.
19 NEWBORN NEURONS MIGRATE LONG DISTANCES TO THEIR FINAL LOCATIONS Newborn neurons migrate long distances to reach their final locations As they migrate, they sample the environment and change the trajectory Once they reach final locations, they stop and begin establishing connections with other neurons Noctor et al, Nature Neuroscience, 2004
20 NEWBORN NEURONS MAKE THOUSANDS OF CONNECTIONS WITH EACH OTHER University Hospital, Freiburg
21 BRAIN INITIATIVE Science News, Laura Sanders, 2014
22 STEPS IN ADULT NEUROGENESIS Enikolopov lab Cold Spring Harbor laboratory What nutrient and environmental factors regulate neurogenesis? NATURE NEUROSCIENCE VOLUME 10 NUMBER 3
23 IMPACT OF ENVIRONMENT ON ADULT NEUROGENESIS Stangl and Thuret et al, Genes Nutr Dec; 4(4):
24 CHOLINE AND CELLULAR FUNCTIONS Jiang et al, 2014
25 AMOUNTS OF CHOLINE IN FOODS mg/100 g food Beef Liver Daily requirement estimated at 550 mg Egg Wheat germ Bacon Soy Bean (dried) Cod Ground beef Chicken Peanut Butter Milk chocolate Tofu Bread Spinach Cow Milk Journal of Nutrition, 133: , 2003
26 MATERNAL DIET AND ADULT NEUROGENESIS Choline sufficient (control) Choline deficient Choline supplemented DCX DCX DCX DCX = doublecortin, a marker of newborn neurons in the hippocampus Maternal intake of choline determines the extent of adult neurogenesis in her offspring. Glenn et al, European J Neuroscience, 2007
27 EFFECT OF CHOLINE LASTS A LIFE TIME Memory loss No memory loss From Meck and Williams Neurosci Biobehav Rev. 27(4):385-99, 2003 (Steve Zeisel)
28 THE EFFECTS OF REDUCED CHOLINE INTAKE DURING PREGNANCY Period of reduced choline intake
29 FEWER NEURAL PROGENITOR CELLS ARE PRESENT IN Normal brain Low choline brain Neurons Stem cells Stem cells Neurons All cells
30 FEWER CORTICAL NEURONS ARE PRODUCED IN LOW CHOLINE BRAINS Normal brain Low choline brain VZ VZ Cortical Neurons/ All cells
31 NUMBERS OF NEURONS REMAIN LOW INTO ADULTHOOD Normal brain Low choline brain Adult Cortical neurons All cells
32 SUMMARY OF THE ROLE OF CHOLINE IN BRAIN DEVELOPMENT AND FUNCTION Requirement for choline is very high during pregnancy and lactation Choline is required for optimal development of the brain Low choline diet alters cortical and hippocampal development and later function Choline supplementation during development ensures proper cognitive function throughout life Are there other nutrients that affect neurogenesis and cognitive function?
33 OMEGA-3 FATTY ACIDS Essential fatty acids (DHA) Found in fish, nuts, seeds (flax seeds), green leafy vegetables Improve neurogenesis and cognitive performance through a variety of mechanisms
34 ZINC Improves mood Alleviates symptoms of depression Increases adult neurogenesis Zinc deficiency => depression and reduced adult neurogenesis
35 VITAMIN E FLAVONOIDS Improve cognitive function and increase neurogenesis
36 OTHER NUTRIENTS PROMOTING ADULT NEUROGENESIS EGCG compound present in green tea Curcumin component of turmeric Vitamin A Blueberries
37 OTHER DIETARY CONSIDERATIONS: 1. REDUCED CALORIC INTAKE Improves learning, memory and motor performance
38 2. FASTING 5 days every month for 3 months 34% and 54% of the normal caloric intake at least 9% 10% proteins, 34% 47% carbohydrates, and 44% 56% fat Brandhorst et al, Cell Metabolism, 2015 Jul 7;22(1):86-99.
39 LIFESTYLE CONSIDERATIONS Positive: Physical activity/exercise!!!!! Cognitive enrichment learning new tasks, games, puzzles etc. Negative: Stress Sleep deprivation High fat/high sugar diet Alcohol consumption
40 ACKNOWLEDGMENTS Zeisel lab Funding sources NIH NC Biotechnology Center Industry partners Private donations Thank you!
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