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Samenvatting van alle colleges - Drugs for the Central Nervous System (WBFA033-05)

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Samenvatting van alle colleges van het vak Drugs for the Central Nervous System gegeven aan de Rijksuniversiteit Groningen

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Subido en
22 de abril de 2024
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2022/2023
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Lecture 1: Introduction to CNS diseases and their therapies
Dolga, 11/05

Sections of the brain
- Midsagittal section , dividing the left and the right
- Frontal (coronal) section  dividing the for and back of the brain.
- Transverse (horizontal) section  divide the top and bottom.

Radial symmetrical  e.g. seastar.
Lateral symmetrical  e.g. mammals (more complex movements and are better coordinated).

Parts of the brain
- Forebrain  decision making.
- Midbrain.
- Hindbrain  e.g. circulation, digestion, breathing.
• Closest to spinal cord  vital functions.
- Spinal cord.
Embryo’s already have these parts. Structural change when
becoming adult  forebrain becomes huge, midbrain stays small,
and hindbrain increases in size.

Brain anatomy
- Cerebral cortex (80% of the brain)
• Frontal lobe  emotion and decision making.
• Parietal lobe  sensory/coordination.
• Occipital lobe  vision.
• Temporal lobe  memory and hearing, language
• Cerebellum, spinal cord.
- Sulci are the grooves in the cerebral cortex (around parietal)
- Gyri are the folds of the cerebral corte  makes larger area with more neurons.
- Somatosensory cortex in paritel lobe  collects information from sensory neurons.
- Motor cortex in frontal lobe  provides information on how to act to motor neurons.

Structures of the brain

1. Brainstem
- 2 main functions:
• Basic functions  blood circulation, breathing,
heartbeat etc.
• Sensory/motor nerves -> filtering and routing
information.
- 3 parts from top to bottom: midbrain, pons, medulla
oblangata.
- Structure close to brain stem  more vital functions.

2. Cerebellum
- 2 main functions:
• Motor coordination voluntary movements.
• Motor memory.
- Cerebellum also called arbor vitea.
- The left and right-side work contralateral with cerebral cortex. Ipsilateral (same side) with
spinal cord.
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,3. Thalamus
- Function  sort data.
- Contains hypothalamus (thermoregulation) and pituitary gland (hormonal activity).

4. Cerebrum
- Function  integrate all information from sensory part, makes sense to what we
see/hear/feel etc.
- MRI used to study functions of cerebrum and brain activity. Thickness of cortex can also be
studied.
• Grey matter  cell bodies of neurons.
• White matter  axons of the neurons containing myelin.
- Functional MRI (fMRI)  shows changes in blood flow to local parts of the brain 
indication of brain activity.
- Diffusion Tensor Imaging (DTI)  measures microscopic movement of water in the brain,
also to study white matter.

5. Cerebral cortex
- Consists of the 5 parts.
- 6-layered sheet about 5 mm thick.
- Total covers threequarters of the brain.
- Essential for consciousness.

6. Corpus Collosum
- Right hemisphere  facial recognition.
- Left hemisphere  reasoning, logic.
- Broca’s area  production of speech.
- Wernicke’s area  to understand speech and read.
- Wernicke’s area and Geschwind’s area  to create meaningful speech.
- Neocortical areas

7. Basal ganglia
- Involuntary movements.
- Diseases  Huntington’s, PK.
- Consists of caudate (blue), putamen (red) and internal capsule forming
together the striatum.
- On top of basal ganglia are nucleus accumbens  reward behavior and
coordinate addiction.

8. Midbrain – substantia nigra
- Function  dopamine production. Important for movement.
- Substantia nigra is black when you cut it without staining. This is because of
the neuromelanin  protects dopaminergic neurons against damage
produced by oxidative stress.
- Disease  PK  no black color  no neuromelenanin  dopaminergic
neurons get degenerated.

9. Place cells
- Multipolar neuron within the hippocampus that activates when an animal enters a particular
place in its environment.  place field.
- In temporal lobe.



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,10. Hippocampus
- Responsible for memory.
- In AD brain areas reduced  memory problems.
- In ischemia (stroke)  neurons in the CA1 area died.

Physiology of specific brain regions

- Dorsal vs ventral functions.
- Lower vs higher functions.
- Cortical vs subcortical functions.

Dorsal vs ventral functions
Terminology
- Dorsal part = upper part.
- Ventral part = lower part.
- Rostral part = anterior (voorkant) part.
- Caudal = posterior (achterkant).
Functions
- Dorsal spinal cord and posterior cerebral cortex
• Afferent (inward) sensory signals
• Cerebral processing of sensory output.
- Ventral spinal cord and anterior cerebral cortex.
• Efferent (outward) motor signals.
• Cerebral generation of behavioral output.

Lower vs higher functions
- Spinal cord  specific motor and autonomic control centers.
- Brainstem  control/coordination of autonomic regulation.
- Cerebellum  control/coordination of movements.
- Forebrain  control of complex emotional response, control of rational behavior,
generating mind activity and speech.

Cortical vs subcortical functions
- Cerebral cortex and dorsal thalamus 
• Processing sensory input.
• Perception, planning and executing rational behavior.
• Inhibiting complex emotional response.
- Subcortex 
• Extrapyramidal control of rational behavior and intensity of motor function.
• Generating complex emotional response (amygdala).
• Recognition and memory formation (Hippocampus).

Voluntary motor behavior
- Frontal cortex (glutamate)  initiates motor output.
- Cerebellum (GABA)  coordinates different movements.
- Basal ganglia (dopamine)  coordinates different contractions.




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, Extrapyramidal system
- Extrapyramidal circuits: cortex  striatum  pallidum  thalamus  cortex.
- Direct by activation (dopamine 1) and indirect by inhibition (dopamine 2).

A few facts about the brain
- Adult brain weighs 1300-1400 g (2% of whole body weight).
- Volume is 1400 ml (78% is water, 12% lipid and 8% protein.)
- 85-100 billion neurons in the brain.
- Uses 20% of total resting oxygen.

Functional distinctions: somatic and autonomic NS
- Autonomic nervous system  subconscious and involuntary
• Motility, secretory, metabolic.
- Somatic nervous system  conscious and voluntary
• Skeletal muscle.

Brain function
Cranial bones (skull) protect the brain. Beneath the bones are meninges (membranes):
- Dura mater  least close to brain, closest to skull.
- Arachnoid
- Pia mater  closest to brain.

Blood supply to the brain
- Brain receives 20% of blood flow from the heart.
- 750-1000 ml/min.
- BBB has tight junctions between blood vessel endothelial cells that limit the flow of
substances into the brain.
- Astrocytes  linked to neurons so that neurons have no direct contact with BBB.

Passing the BBB
1. Tight junctions between endothelial cells  water-soluble compounds. Least used.
2. Transcellular lipophilic pathway  lyophilic agents. Most used.
3. Transport proteins  glucose, amino acids etc.
4. Receptor mediated transcytosis.  insulin, transferrin.
5. Adsorptive transcytosis  plasma proteins.

Astrocyte  main component of brain tissue  communication with neurons and vessels.
- Carries neurons and vessels, constitutes BBB, produced neurotropic factors, is
neurochemically competent (helps neurons to produce action potential).

Oligodendrocyte  produce cerebral myelin sheets.
- Can act on multiple neurons. In multiple sclerosis inflamed.
- Schwann cells of the CNS.

Micro ganglia  Horega cells (brain immune cells)
- Important for inflammation, can change shape and can phagocytose cell debris or
dying neurons.

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