Lectures Nutrition & Brain
Introduction Course & GWA’s
Mental disorders
Around 1 in 7 people (15%) have 1 or more mental (or substance use) disorders
970 million people have a mental disorder worldwide
Prevalence: mostly anxiety disorders (3.8%), depression (3.4%), then alcohol & drug use disorder
Disease burden (DALYs): highest for neurological disorders, even higher than e.g. HIV, heart disease,
cancer
Dietary supplements: multi-billion dollar business
- 2018: ≈85,000 types of dietary-supplement products were sold in the United States alone
- > $40 billion in retail sales in the United States and $121 billion worldwide
- Many nutrition-related health claims
- Evidence based?
→ the dietary supplement market is also growing in Europe
Use of dietary supplements
Representative sample of adults above 18 on their use of dietary supplements:
- 78%: supplements at least somewhat important to health (81% in people aged ≥50y)
- 58% take a dietary supplement ≥3 times a week (69% in people aged ≥50y)
23% of adults age ≥18 take a supplement for any of the four brain-related reasons
Four brain-related reasons: maintaining brain health, improving brain health, reversing dementia,
delaying dementia
What do they take? → omega-3, fish-oil, curcumin, green tea etc.
Learning outcomes:
- Explain the basic neurochemistry and brain anatomy, morphology and function
- Explain the gut-brain axis and the effects of dietary factors on this axis, and integrate the role
of the gut microbiome in brain-related disorders
- Evaluate the impact of nutrition and nutritional compounds on brain function and brain-
related disorders
- Critically evaluate and discuss nutritional effects on brain function and cognition
- Design a study and intervention addressing the nutritional effects on cognition and a brain-
related disorder
, Basic principles of brain function
Brain tissue: supported by neurons (100 billion)
CNS glia cells:
- Astrocytes (Central nervous system (CNS), support)
- Oligodendrocytes (CNS, myelin, action potential)
- Microglia (CNS, immune system of the brain, neuroinflammation)
- Ependymal cells (CNS, outer layer of the brain, ventricles, cerebrospinal fluid)
PNS glia cells (periphery):
- Schwann cells (Peripheral nervous system (PNS), myelin)
- Satellite cells (PNS, support)
Neurons: unipolar, bipolar, pseudounipolar, multipolar
Cell body at the top → myelin sheet → axon terminal
Astrocyte: on the neurons, end-feet
Oligodendrocytes: produce myelin along the axons, are in the middle of the myelin structuring fibers
Microglia: small, can change morphologically
Ependymal cell: outer layer or ventricles, produce CSF (150 mL flowing through brain, refreshed 4
times a day)
Neuronal communication
Action potential propagation → vesicles with neurotransmitters (dopamine, serotonine) towards
membrane → released into synaptic cleft → reaches dendrite of other neuron: can decide if the
signal is stimulating enough to proceed
Neurotransmitters: dopamine (addiction, Parkinson), serotonin (depression)
Neurotransmitters or precursors obtained by diet: tryptophan via egg white → transported over BBB
→ transformed into serotonin
Neurotransmitter release
Action potential to synapse → membrane depolarization → influx of calcium = signal for vesicles →
docking of the vesicles → opening of the vesicles in synaptic cleft → can bind to post-synaptic cell, if
enough: cycle begins again
Neurotransmitter that is in the synaptic cleft can be taken up by the cell that released it again (re-
uptake)
Syntaxin: stimulates docking of the vesicles
Cocaine: blocks the re-uptake receptor → more dopamine stays in the synaptic cleft
,Instant synthesis: endocannabinoids
Can be instantly formed. When action potential reaches post-synaptic cell → endocannabinoids can
be synthesized on the membrane → retrograde signalling to pre-synaptic cell
Purpose is broad, e.g. involved in addiction and food preferences
Stimulated by cannabis, makes you crave certain foods
But also: pain-relief
Synaptic plasticity
- After long-term potentiation (LTP), synaptic communication is strengthened (more receptors,
more synapses)
- Base of learning and memory processes
- Challenge and stimulate your brain, else synapses degenerate
Brain tissue: not many cell types involved, but they are really intertwined with each other
Grey & white matter
Grey matter: a lot of neurons, outside of the brain
White matter: myelin, contains projections, middle of the brain
Quiz (true/false)
1. An axon is covered with myelin → true
2. Myelin is produced by astrocytes → false, produced by oligodendrocytes
3. Dopamine is instantly synthesized and completely degenerated after release → false
4. Grey matter is mainly ‘in the core’ of the brain → false, white matter is in the core
Blood-Brain-Barrier
Entry into the brain: molecules diffuse across membranes (e.g., oxygen and other gases, lipid-
permeable compounds)
- Transporter molecules (e.g., glucose transporters)
- High electrical charge slows down diffusion across membranes
- Highly restricted: neuroactive compounds (e.g., glutamate, adrenalin, dopamine)
Filmpje BBB:
Acts as a barrier between bloodstream and extracellular space
Prevents toxins, pathogens from crossing into the brain
Tight junctions of endothelial cells form the barrier
Astrocytes have end-feet (projections) to the endothelial cells (involved in signalling, forming the
tight junctions) to cover up the capillaries
Circumventricular organs (CVOs): lack BBB because functions require access to the bloodstream,
molecules can cross at that point into the brain
, Lipids diffuse across membranes
Within the brain involved in:
- Neuronal membranes (e.g. phospholipid bilayer, membrane fluidity, synaptic plasticity
and/or vesicle formation)
- Myelin (e.g. sphingolipids, a major component of myelin membrane formed by mature
oligodendrocytes)
- Endocannabinoids (e.g. precursor arachidonic acid)
Glucose: needs transporter
Brain: High energy demand
o ~2% of the body weight
o ~20% of glucose-derived energy (~5.6 mg glucose per 100 g human brain tissue per
minute)
Glucose is mainly metabolized by mitochondria (oxygen-dependent metabolism, ATP)
Alternative sources: lactate, ketones, medium fatty acids, acetate
Glucose transport
Glucose: actively transported over BBB from the bloodstream by GLUT1 → in brain tissue → taken
up by:
- Astrocytes with GLUT1
- Taken up by neurons with GLUT3 (higher rate of transporting glucose → more glucose enter
neurons than astrocytes)
- Oligodendrocytes with GLUT1
Glucose in blood are lower → sensed by neurons in hypothalamus (AgRP and POMC) → regulate
neuroendocrine signals (hormones) via bloodstream or via vagal nerve → cause the feeling of hunger
Astrocytes & glucose
- Low glucose levels → astrocytes produce lactate (glycogen storage)
- Lactate: provided to neurons, metabolized by neurons and oligodendrocytes to produce
energy (to produce action potentials, to fire)
- High glucose levels → astrocytes store as glycogen
Pathologies
Alzheimer’s disease:
- Reduction in cerebral glucose metabolism (early)
- Disturbed glucose metabolism is associated with AD progression (reduced GLUT1 expression
in BBB and astrocytes)
Parkinson’s disease:
- Widespread cortical hypometabolism
- Glucose hypermetabolism in the external pallidum
Glucose
Mitochondria
Glucose (oxygen-dependent metabolism, ATP)
Oxidative stress
- Oxidative phosphorylation in the mitochondria: by product reactive oxygen species (ROS)
- Low amounts ROS = essential in neuronal development and function
- Normal conditions: ROS production neutralized by the antioxidant system
- Oxidative stress: ROS production exceeds capacity of antioxidant response system, extensive
protein oxidation and lipid peroxidation occurs, causing oxidative damage, cellular
degeneration, and even functional decline
Introduction Course & GWA’s
Mental disorders
Around 1 in 7 people (15%) have 1 or more mental (or substance use) disorders
970 million people have a mental disorder worldwide
Prevalence: mostly anxiety disorders (3.8%), depression (3.4%), then alcohol & drug use disorder
Disease burden (DALYs): highest for neurological disorders, even higher than e.g. HIV, heart disease,
cancer
Dietary supplements: multi-billion dollar business
- 2018: ≈85,000 types of dietary-supplement products were sold in the United States alone
- > $40 billion in retail sales in the United States and $121 billion worldwide
- Many nutrition-related health claims
- Evidence based?
→ the dietary supplement market is also growing in Europe
Use of dietary supplements
Representative sample of adults above 18 on their use of dietary supplements:
- 78%: supplements at least somewhat important to health (81% in people aged ≥50y)
- 58% take a dietary supplement ≥3 times a week (69% in people aged ≥50y)
23% of adults age ≥18 take a supplement for any of the four brain-related reasons
Four brain-related reasons: maintaining brain health, improving brain health, reversing dementia,
delaying dementia
What do they take? → omega-3, fish-oil, curcumin, green tea etc.
Learning outcomes:
- Explain the basic neurochemistry and brain anatomy, morphology and function
- Explain the gut-brain axis and the effects of dietary factors on this axis, and integrate the role
of the gut microbiome in brain-related disorders
- Evaluate the impact of nutrition and nutritional compounds on brain function and brain-
related disorders
- Critically evaluate and discuss nutritional effects on brain function and cognition
- Design a study and intervention addressing the nutritional effects on cognition and a brain-
related disorder
, Basic principles of brain function
Brain tissue: supported by neurons (100 billion)
CNS glia cells:
- Astrocytes (Central nervous system (CNS), support)
- Oligodendrocytes (CNS, myelin, action potential)
- Microglia (CNS, immune system of the brain, neuroinflammation)
- Ependymal cells (CNS, outer layer of the brain, ventricles, cerebrospinal fluid)
PNS glia cells (periphery):
- Schwann cells (Peripheral nervous system (PNS), myelin)
- Satellite cells (PNS, support)
Neurons: unipolar, bipolar, pseudounipolar, multipolar
Cell body at the top → myelin sheet → axon terminal
Astrocyte: on the neurons, end-feet
Oligodendrocytes: produce myelin along the axons, are in the middle of the myelin structuring fibers
Microglia: small, can change morphologically
Ependymal cell: outer layer or ventricles, produce CSF (150 mL flowing through brain, refreshed 4
times a day)
Neuronal communication
Action potential propagation → vesicles with neurotransmitters (dopamine, serotonine) towards
membrane → released into synaptic cleft → reaches dendrite of other neuron: can decide if the
signal is stimulating enough to proceed
Neurotransmitters: dopamine (addiction, Parkinson), serotonin (depression)
Neurotransmitters or precursors obtained by diet: tryptophan via egg white → transported over BBB
→ transformed into serotonin
Neurotransmitter release
Action potential to synapse → membrane depolarization → influx of calcium = signal for vesicles →
docking of the vesicles → opening of the vesicles in synaptic cleft → can bind to post-synaptic cell, if
enough: cycle begins again
Neurotransmitter that is in the synaptic cleft can be taken up by the cell that released it again (re-
uptake)
Syntaxin: stimulates docking of the vesicles
Cocaine: blocks the re-uptake receptor → more dopamine stays in the synaptic cleft
,Instant synthesis: endocannabinoids
Can be instantly formed. When action potential reaches post-synaptic cell → endocannabinoids can
be synthesized on the membrane → retrograde signalling to pre-synaptic cell
Purpose is broad, e.g. involved in addiction and food preferences
Stimulated by cannabis, makes you crave certain foods
But also: pain-relief
Synaptic plasticity
- After long-term potentiation (LTP), synaptic communication is strengthened (more receptors,
more synapses)
- Base of learning and memory processes
- Challenge and stimulate your brain, else synapses degenerate
Brain tissue: not many cell types involved, but they are really intertwined with each other
Grey & white matter
Grey matter: a lot of neurons, outside of the brain
White matter: myelin, contains projections, middle of the brain
Quiz (true/false)
1. An axon is covered with myelin → true
2. Myelin is produced by astrocytes → false, produced by oligodendrocytes
3. Dopamine is instantly synthesized and completely degenerated after release → false
4. Grey matter is mainly ‘in the core’ of the brain → false, white matter is in the core
Blood-Brain-Barrier
Entry into the brain: molecules diffuse across membranes (e.g., oxygen and other gases, lipid-
permeable compounds)
- Transporter molecules (e.g., glucose transporters)
- High electrical charge slows down diffusion across membranes
- Highly restricted: neuroactive compounds (e.g., glutamate, adrenalin, dopamine)
Filmpje BBB:
Acts as a barrier between bloodstream and extracellular space
Prevents toxins, pathogens from crossing into the brain
Tight junctions of endothelial cells form the barrier
Astrocytes have end-feet (projections) to the endothelial cells (involved in signalling, forming the
tight junctions) to cover up the capillaries
Circumventricular organs (CVOs): lack BBB because functions require access to the bloodstream,
molecules can cross at that point into the brain
, Lipids diffuse across membranes
Within the brain involved in:
- Neuronal membranes (e.g. phospholipid bilayer, membrane fluidity, synaptic plasticity
and/or vesicle formation)
- Myelin (e.g. sphingolipids, a major component of myelin membrane formed by mature
oligodendrocytes)
- Endocannabinoids (e.g. precursor arachidonic acid)
Glucose: needs transporter
Brain: High energy demand
o ~2% of the body weight
o ~20% of glucose-derived energy (~5.6 mg glucose per 100 g human brain tissue per
minute)
Glucose is mainly metabolized by mitochondria (oxygen-dependent metabolism, ATP)
Alternative sources: lactate, ketones, medium fatty acids, acetate
Glucose transport
Glucose: actively transported over BBB from the bloodstream by GLUT1 → in brain tissue → taken
up by:
- Astrocytes with GLUT1
- Taken up by neurons with GLUT3 (higher rate of transporting glucose → more glucose enter
neurons than astrocytes)
- Oligodendrocytes with GLUT1
Glucose in blood are lower → sensed by neurons in hypothalamus (AgRP and POMC) → regulate
neuroendocrine signals (hormones) via bloodstream or via vagal nerve → cause the feeling of hunger
Astrocytes & glucose
- Low glucose levels → astrocytes produce lactate (glycogen storage)
- Lactate: provided to neurons, metabolized by neurons and oligodendrocytes to produce
energy (to produce action potentials, to fire)
- High glucose levels → astrocytes store as glycogen
Pathologies
Alzheimer’s disease:
- Reduction in cerebral glucose metabolism (early)
- Disturbed glucose metabolism is associated with AD progression (reduced GLUT1 expression
in BBB and astrocytes)
Parkinson’s disease:
- Widespread cortical hypometabolism
- Glucose hypermetabolism in the external pallidum
Glucose
Mitochondria
Glucose (oxygen-dependent metabolism, ATP)
Oxidative stress
- Oxidative phosphorylation in the mitochondria: by product reactive oxygen species (ROS)
- Low amounts ROS = essential in neuronal development and function
- Normal conditions: ROS production neutralized by the antioxidant system
- Oxidative stress: ROS production exceeds capacity of antioxidant response system, extensive
protein oxidation and lipid peroxidation occurs, causing oxidative damage, cellular
degeneration, and even functional decline
