W19 Intro to CNS

Question 1

Key topics covered in CNS ISU (for info)

Answer 1

• Drug delivery to the CNS
• Epilepsy
• Dementia
• Parkinson’s disease
• Depression (bipolar and unipolar)
• Schizophrenia
• Tolerance and dependence and reward
• Drug and alcohol dependence
• Anxiety and insomnia
• Migraine/headaches
• Controlled drugs

Question 2

Why is the CNS important? (for info)

Answer 2

• CNS disorders huge burden on social services and the economy
  -0.5-1% epileptic - 1000 unexplained deaths p.a.
  -1% schizophrenic - 10% incidence of suicide
  -Many individuals suffer age-related dementia
  -0.1% of population Parkinson’s and related syndromes
• CNS active drugs are important:
  -1 in 6 prescriptions.
• The CNS one of the most complex organs in the body :
  -relationships between cellular actions and behavioural effects less than clear

Question 3

Neurone features and Synapses recap:
(for info)

Answer 3

Neurone:
Cell body/soma
Myelin
Dendrite
Synapse

Def= Where one neurone meets another –
synapse
Pre synaptic neuron- Post synaptic neuron
-Gap – synaptic cleft
* Neurotransmitter released from A, diffuses across gap binds to receptors on B
-Ionotropic and GPCR receptors

Question 4

Features of Ionotropic receptors - excitatory synapses?
Examples?

Answer 4

• Transmitter depolarizes and excites
• Inward positive current
• Excitatory postsynaptic potential (EPSP)

-Glutamate
-Aspartate
-Acetylcholine (nicotinic)

Question 5

Synaptic summation
Different types? (3)

Answer 5

Temporal summation, Spatial summation
EPSP-IPSP cancellation= no AP generated in neurone

Excitatory transmission glutamate + Inhibitory transmission GABA = Recording potential of post-synaptic cell

Question 6

Why is the CNS so complex? (7)

Answer 6

1. Neurones are highly complex structures
2. Multiple synapses on each neurone
3. Several different types of synapse
4. Multiple transmitters
5. Multiple receptors
6. Multiple messenger systems
7. Neurones interconnected in complex networks

Question 7

G-Protein Coupled Receptors
What can they be linked to? (2)

Answer 7

*Linked to ion channels
-K+
-Ca++
*Linked to enzymes
-adenylyl cyclase
-phospholipase C

Question 8

Sites of action of CNS drugs: Synapse Structure

Answer 8

1. Substrate transporter
2. Synthesis pathway
3. Vesicular transporter
4. Vesicular movement
5. Release process
6. Postsynaptic ionotropic receptors
7. Postsynaptic GPCR
8. Second messenger systems
9. Uptake transporter
   10.Enzymatic degradation
   11.Presynaptic receptors
   12.Membrane ion channels

Drugs can have an effect all of the above

Question 9

Drug Delivery: What is The Blood Brain
Barrier (BBB)?

Answer 9

• BBB: network of vessels that form a
  structural and chemical barrier between the
  brain and systemic circulation
  -Nerve cells in brain: require stable environment
  -Protects brain but also a barrier to neuroactive pharmaceuticals

Cells
* Astrocyte
* Pericyte
* Capillary endothelial cell

Question 10

The Blood Brain Barrier: Key Differences
between brain and general capillaries?

Answer 10

General capillary
* Fenestrated or continuous
* small solutes can diffuse through intercellular clefts
* pinocytosis independent of molecular size (pass large molecules)

Brain capillary
* Continuous
* no fenestra
* tight junctions
* reduced pinocytosis
* astrocyte foot processes