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Impact of vitamins & nutrients on neurological function Lecture Series Outline Week 1: Introduction to the brain Week 2: B-vitamins and development (Guest Lecture: Usha Shan) Week 3: B-vitamins and aging Week 4: Choline Week 5: Vitamin E and D Week 6: Effect of over supplementation of vitamins and nutrients

Questions Please save your questions for before the break or end of lecture

Lecture Materials http://carleton.ca/linr/early-spring-2017-session/class-notes/ Password: spring

Impact of vitamins & nutrients on neurological function INTRODUCTION TO THE BRAIN Nafisa Jadavji, PhD nafisa.jadavji@carleton.ca

Outline of Lecture How does the brain learn? Organization of the brain Structures & function within the brain Behaviour Units of Brain function BREAK Communication between cells How does the brain develop? How is brain function affected? Basic Brain research (Neuroscience)

How does the brain learn? https://www.youtube.com/watch?v=cglykv689s4

Take home message The brain is complex

Nervous System

What is the brain?

What does the brain look like?

Different orientations of brain

How the brain is protected?

Cerebrospinal fluid (CSF) Protection basic mechanical immunological protection Regulates blood flow

Ventricles

Cross section of the brain

Homunculus Motor Cortex Sensory Cortex

Two Point Discrimination 42mm 3mm

How is the brain organized?

Structures of the brain

Behaviour Kind of movement in a living organism Have a cause and function

Behaviour Can be learned Vary in degree of complexity

Behaviour: Research Example Skilled Reaching Task In Rodents

Units of Brain Function Neurons Glial cells

Units of Brain Function: Neurons

Units of Brain Function: Glial Cells (support cells)

Break

Components of the Synapse

How neurons in the cell communicate: the synapse

How neurons in the cell communicate: the synapse

Neurotransmitters Acetylcholine à memory, PNS Dopamine à reward Norepinepherine (a.k.a., noradrenaline) à stress response Serotonin à mood balance

Brain development

Brain Development

What s going on at the cellular level? Brain and Behaviour, Kolb & Whishaw, 2001

What s going on at the cellular level? Brain and Behaviour, Kolb & Whishaw, 2001

Brain/behaviour development after birth

The brain and serotonin Frontal lobe Memory Cognition Hypothalamus Hunger Temp. Thirst Hippocampus Memory Amygdala Emotion Spinal Cord

Serotonin neurotransmission Axon Serotonin Dendrite Serotonin Reuptake transporters Serotonin receptors

Ecstasy Affects: Neurotransmission Ecstasy Serotonin Axon E E Dendrite E E E E Re-uptake transporters Serotonin receptors

Ecstasy and Serotonin transmission Axon Serotonin Dendrite Reuptake transporters Serotonin receptors

Reward circuitry Prefrontal cortex dopamine nucleus accumbens VTA dopamine dopamine

Discovery of the Reward Pathway

Stress Stress comes from both the good and the bad things that happen to us. If we didn t feel any stress, we wouldn t be alive! Stress may feel overwhelming at times, but there are many strategies to help you take control. -Canadian Mental Health Association

What happens when you re under stress? heart beats faster blood pressure increases breathe faster pumping maximum oxygen and energy-rich blood to your muscle liver releases more sugar into your blood ready for action.

Stress Response CRF: Corticotrophin Releasing Factor ACTH: Adrenocorticotropic hormone

Stress Response body s stress response is perfect in the short-term damaging if it goes on for weeks or years. High levels of cortisol for prolonged periods can: damp down your immune system decrease the number of brain cells so impairing your memory affect your blood pressure and the fats in your blood making it more likely you will have a heart attack or stroke

Stress excites brain cells to death - cortisol released in stress travels into the brain and binds to the receptors inside many neurons - cascade of reactions, this causes neurons to admit in more calcium In the short-term cortisol presumably helps the brain to cope with the life-threatening situation. However, if neurons become over-loaded with calcium they fire too frequently and die they are literally excited to death.

Stress Response: Growing new brain cells Contrary to traditional ideas, the adult brain does make new neurons, but only in very restricted areas. For example, the hippocampus of an adult rat makes between 5000-10 000 new neurons each day. Joe Herbert s lab in Cambridge has showed that cortisol dramatically decreases the rate new brain cells are made. So perhaps some of the adverse effects of stress are related to fewer brain cells being created in the hippocampus.

Environment: Paraquat Herbicide Association between paraquat use and Parkinson s disease (first observed in Farmers and then confirmed in mice) Paraquat is structurally similar to MPP+, a known fast-acting inducer of Parkinson's disease in primate brains.

Environment: Paraquat Paraquat also induces oxidative stress in invertebrates such as flies. Paraquat-fed flies suffer early-onset mortality and significant increases in superoxide dismutase activity.

Environment: Enrichment

Environment: Enrichment

Brain Research à Neuroscience Developmental neuroscience describes how the brain grows and changes. Cognitive neuroscience involves studying how the brain creates and controls thought, language, problem solving, and memory. Molecular and cellular neuroscience explores the genes, proteins, and other molecules involved in the functioning of neurons. Behavioral neuroscience examines the brain areas and processes underlying the behavior of animals and humans. Clinical neuroscience is the area of study in which medical specialists such as neurologists and psychiatrists use basic neuroscience research findings to explore how to treat and prevent neurological disorders and to rehabilitate patients whose nervous system has been damaged or injured.

Model Systems: in vivo

Model Systems: in vitro Grow in culture Mate Mice 24 hours Dissect embryos @ e17 Treatment

Disease Models: Stereotaxic Surgeries

Disease Models Ischemic Damage: Photothrombosis

Disease Models Stroke: Middle cerebral artery (MCAO)

Disease Models Parkinson s disease Substantia Nigra

Behaviour: Ladder Beam Walking Task

Behaviour: Anxiety/Exploratory Elevated Plus Maze Open field

Behaviour: Learning and Memory Morris Watermaze

Tools to Study the Brain MRI Protein Levels: Western Blot Tissue Morphology

QUESTIONS? nafisa.jadavji@carleton.ca

Next Class... March 9 th B-vitamins (Guest Lecture: Usha Shan) -Folic acid and other B-vitamins during development