FOOD AND BRAIN HEALTH
WEEK 1 – Basic neuroanatomy 2
WEEK 2 – Measuring 12
WEEK 3.1 – Cognitive ageing, and the impact of lifestyle on the ageing brain 16
WEEK 3.2 - Gut-Brain axis in ageing 22
WEEK 4.1 – The immune-brain axis 29
WEEK 4.2 – The immune-brain axis in obesity: The obesity spiral 34
WEEK 5.1 – Short chain fatty acids 40
WEEK 5.2 – Short-chain fatty acids in the human gut-brain axis 46
, WEEK 1 – Basic neuroanatomy
Lifestyle factors (nutrition, exercise) & Cognition
Cognition, Reward, Motivation:
● Hippocampus, Caudate nucleus, Nucleus accumebens & striatum
Gut-Brain-Axis: bidirectional communication system between the gastrointestinal tract and
the CNS that links the nervous, endocrine, and immune system. Allows the brain to influence
the gut, and vice versa.
● Nutrients (glucose, fatty acids like short chain fatty acids, omega-3 fatty acids) and
precursors of NTs)
● Blood circulation
● Immune response
Neurons and glial cells
● Neurons: 87 billion neurons, located in white and grey matter
● Glial cells: 1 trillion glial cells, ratio 10 glial cells : 1 neuron & 1 capillary : 1 neuron
● Dendrites receive the signal → proceed signal to cell body → important enough to
produce an AP? → if it is, AP at axon hillock → will jump via nodes of Ranvier
towards end of axon → chemical transmission between pre- and postsynapse
● White matter: mainly all axons covered in myelin that are packed together
● Grey matter: more cell bodies, less myelin
CNS glia
Astrocyte Oligodendrocyte Microglia Ependymal cell
PNS glia Satellite cell Schwann Cell / /
Functions Maintain extracellular Create myelin for Immune Create and circulate
environment, remove quick conduction of surveillance and cerebrospinal fluid
excess NTs, direct neuronal nerve impulses in the phagocytosis (CSF)
growth, induce BBB in CNS brain and spinal cord
Neuroinflammation: complex reaction of the CNS as response to certain stimuli. It is mainly
regulated by astrocytes and microglia, initiated by variety of cues (e.g. infection, traumatic
brain injury, toxic metabolites, or oxidative stress
1
,Positive Aspects
● Transient (low) inflammation ⇒ immune to brain communication and immune
surveillance → IL-1 → reorganization of host priorities
● Neuroinflammatory (low) signaling ⇒ development, memory and learning → IL-1
and IL-4 → enhanced plasticity
● Transient (med) inflammation ⇒ injury induced remodeling → IL-4 redirected to M2
→ tissue repair
● Transient (med) inflammation ⇒ immune pre-condition, euflammation →
neuroprotection
○ Euflammation: causes innate immune alterations without obvious
neuroimmune activation, protecting against both bacterial infection and
endotoxin induced neuroinflammation
Negative Aspects
● Transient (high) inflammation ⇒ traumatic CNS injury → IL-1, TNF, ROS, iNOS →
collateral damage
● Transient (med) inflammation ⇒ repeated social defeat stress → CCL2 and IL-2 →
anxiety & depression
● Chronic (low) inflammation ⇒ aging, traumatic brain injury → IL-1 and IL-6 →
cognitive impairment reduced plasticity
● Chronic (high) inflammation ⇒ neurodegenerative disease → IL-1, TNF, IFNγ →
neuronal damage
Chronic neuroinflammation: the immune system stays activated longer than it should. Glial
cells activate a stronger immune response as the brain’s first immune response doesn’t work
● brain injury, aging, viruses, toxic metabolites. Associated with neurodegenerative
diseases
● Sustained activation of glial cells + recruitment of other immune cells into the brain
Brain metabolism
● ~2% of the body weight
● ~60% of lipids
● ~20% of glucose-derived energy
Brain has a high energy demand
● Energy → glucose
● 5.6 mg glucose per 100 g human brain tissue per minute
● Loads of blood vessels
2
, Glucose transport in the brain
● The brain is highly protected with the blood-brain-barrier; not everything can
passively enter the brain
● Rule: you need to have a transporter, receptor, or be a gas, or be a very tiny small
lipid like molecule to enter the brain tissue
● Glucose will be in blood → transported towards brain → GLUT1 (glucose transporter
1) in endothelial cells (wall of blood vessels) → picks up glucose from the blood, put
it over the BBB into the brain tissue
○ Can be taken up by:
■ Astrocytes (high chance), form the BBB. Have GLUT1 transporter
■ Neurons with GLUT3 → work harder → take up more glucose
● GLUT3 has a higher affinity for glucose than GLUT1 → ensures
neurons receive glucose even when levels are low
■ Oligodendrocytes with GLUT1
● Glucose is used to produce AP and form NTs, but also to define cell fare/death
○ If glucose levels are very low, then cell can go into apoptosis
● Hypothalamus is important for glucose regulation.
○ Two important neurons that can sense glucose levels: AgRP and POMC
○ If it is low → neuroendocrine signals towards periphery → will tell you to eat
Glucose in the astrocytes
● Astrocytes can take up glucose for its own use or store for later use
● If glucose levels are low in brain tissue → astrocytes produce lactate (glycogen
storage) → transported to neurons as another fuel
● Lactate is metabolized by neurons and oligodendrocytes
● High glucose levels: glycogen storage restored
3
WEEK 1 – Basic neuroanatomy 2
WEEK 2 – Measuring 12
WEEK 3.1 – Cognitive ageing, and the impact of lifestyle on the ageing brain 16
WEEK 3.2 - Gut-Brain axis in ageing 22
WEEK 4.1 – The immune-brain axis 29
WEEK 4.2 – The immune-brain axis in obesity: The obesity spiral 34
WEEK 5.1 – Short chain fatty acids 40
WEEK 5.2 – Short-chain fatty acids in the human gut-brain axis 46
, WEEK 1 – Basic neuroanatomy
Lifestyle factors (nutrition, exercise) & Cognition
Cognition, Reward, Motivation:
● Hippocampus, Caudate nucleus, Nucleus accumebens & striatum
Gut-Brain-Axis: bidirectional communication system between the gastrointestinal tract and
the CNS that links the nervous, endocrine, and immune system. Allows the brain to influence
the gut, and vice versa.
● Nutrients (glucose, fatty acids like short chain fatty acids, omega-3 fatty acids) and
precursors of NTs)
● Blood circulation
● Immune response
Neurons and glial cells
● Neurons: 87 billion neurons, located in white and grey matter
● Glial cells: 1 trillion glial cells, ratio 10 glial cells : 1 neuron & 1 capillary : 1 neuron
● Dendrites receive the signal → proceed signal to cell body → important enough to
produce an AP? → if it is, AP at axon hillock → will jump via nodes of Ranvier
towards end of axon → chemical transmission between pre- and postsynapse
● White matter: mainly all axons covered in myelin that are packed together
● Grey matter: more cell bodies, less myelin
CNS glia
Astrocyte Oligodendrocyte Microglia Ependymal cell
PNS glia Satellite cell Schwann Cell / /
Functions Maintain extracellular Create myelin for Immune Create and circulate
environment, remove quick conduction of surveillance and cerebrospinal fluid
excess NTs, direct neuronal nerve impulses in the phagocytosis (CSF)
growth, induce BBB in CNS brain and spinal cord
Neuroinflammation: complex reaction of the CNS as response to certain stimuli. It is mainly
regulated by astrocytes and microglia, initiated by variety of cues (e.g. infection, traumatic
brain injury, toxic metabolites, or oxidative stress
1
,Positive Aspects
● Transient (low) inflammation ⇒ immune to brain communication and immune
surveillance → IL-1 → reorganization of host priorities
● Neuroinflammatory (low) signaling ⇒ development, memory and learning → IL-1
and IL-4 → enhanced plasticity
● Transient (med) inflammation ⇒ injury induced remodeling → IL-4 redirected to M2
→ tissue repair
● Transient (med) inflammation ⇒ immune pre-condition, euflammation →
neuroprotection
○ Euflammation: causes innate immune alterations without obvious
neuroimmune activation, protecting against both bacterial infection and
endotoxin induced neuroinflammation
Negative Aspects
● Transient (high) inflammation ⇒ traumatic CNS injury → IL-1, TNF, ROS, iNOS →
collateral damage
● Transient (med) inflammation ⇒ repeated social defeat stress → CCL2 and IL-2 →
anxiety & depression
● Chronic (low) inflammation ⇒ aging, traumatic brain injury → IL-1 and IL-6 →
cognitive impairment reduced plasticity
● Chronic (high) inflammation ⇒ neurodegenerative disease → IL-1, TNF, IFNγ →
neuronal damage
Chronic neuroinflammation: the immune system stays activated longer than it should. Glial
cells activate a stronger immune response as the brain’s first immune response doesn’t work
● brain injury, aging, viruses, toxic metabolites. Associated with neurodegenerative
diseases
● Sustained activation of glial cells + recruitment of other immune cells into the brain
Brain metabolism
● ~2% of the body weight
● ~60% of lipids
● ~20% of glucose-derived energy
Brain has a high energy demand
● Energy → glucose
● 5.6 mg glucose per 100 g human brain tissue per minute
● Loads of blood vessels
2
, Glucose transport in the brain
● The brain is highly protected with the blood-brain-barrier; not everything can
passively enter the brain
● Rule: you need to have a transporter, receptor, or be a gas, or be a very tiny small
lipid like molecule to enter the brain tissue
● Glucose will be in blood → transported towards brain → GLUT1 (glucose transporter
1) in endothelial cells (wall of blood vessels) → picks up glucose from the blood, put
it over the BBB into the brain tissue
○ Can be taken up by:
■ Astrocytes (high chance), form the BBB. Have GLUT1 transporter
■ Neurons with GLUT3 → work harder → take up more glucose
● GLUT3 has a higher affinity for glucose than GLUT1 → ensures
neurons receive glucose even when levels are low
■ Oligodendrocytes with GLUT1
● Glucose is used to produce AP and form NTs, but also to define cell fare/death
○ If glucose levels are very low, then cell can go into apoptosis
● Hypothalamus is important for glucose regulation.
○ Two important neurons that can sense glucose levels: AgRP and POMC
○ If it is low → neuroendocrine signals towards periphery → will tell you to eat
Glucose in the astrocytes
● Astrocytes can take up glucose for its own use or store for later use
● If glucose levels are low in brain tissue → astrocytes produce lactate (glycogen
storage) → transported to neurons as another fuel
● Lactate is metabolized by neurons and oligodendrocytes
● High glucose levels: glycogen storage restored
3
