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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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Lecture 1: Introduction to CNS diseases and their therapiesDolga, 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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