Sample/practice exam January 2013, questions PDF

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King’s College London This paper is an example of the type of paper that will be set as part of an examination of the College counting towards the award of a degree. Examinations are governed by the College Regulations under the authority of the Academic Board. This is also an examination of the University of London and comes under its authority. BSc EXAMINATION 5BBM0218 PHYSIOLOGY AND PHARMACOLOGY OF THE CENTRAL NERVOUS SYSTEM SUMMER xxxx TIME ALLOWED: 120 MINUTES (total for Paper 1 and Paper 2)

This examination includes TWO papers: Paper 1: Multiple choice paper (MCQ) (1/3 total marks) Paper 1 is a multiple choice paper. You should attempt ALL of the questions. You are recommended to spend 40 minutes on Paper 1 which is worth 1/3 of the total marks for the examination. Please ensure you enter TEST no. xxx answer sheet provided.

COLLEGE No. xx on the MCQ

Paper 2: Essay Paper (2/3 total marks) Paper 2 is in two sections, section A and section B. You must choose one essay title from the choice of titles provided in section A and one essay title from section B. Use separate booklets for each of the two essays. You are recommended to spend 80 minutes on Paper 2 (40 minutes for each essay) which is worth 2/3 of the total marks for the examination (1/3 for each essay). Please ensure that your candidate number, desk number and the number of the question attempted are marked clearly on your answer booklets. TURN OVER WHEN INSTRUCTED ©xxxx King’s College London

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PAPER 1 - MCQ Section Please write your answer to paper 1 on the MCQ paper provided; 1.

Use a pencil (not pen or crayon) to fill in the pink answer sheet.

2.

Label the Pink Sheet clearly with your name, candidate number, College number and test number as follows: Fill in the grids at the top right with the last four digits of your candidate number, the test number (XXX) and college number (XX). These numbers should be written in pencil in the boxes, and pencil marks made across the tops of the appropriate symbols in the grid.

3.

Answer all the questions using the computer-marked sheet provided. Please follow instructions provided on MCQ answer sheet.

4.

If you wish to change an answer, do not attempt to rub out (erase) it, but cancel it by drawing a line under the letter. You may then choose the alternative if you wish.

NB Under no other circumstances should you make any other marks on the answer sheets, as this may cause the sheet to be rejected by the computer when marking.

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Example of extended matching

Using the information given in the box above, answer the following question: 1) If the cell membrane were permeable to K+ only what would be the resting membrane potential of the cell at equilibrium? A) B) B) C) D) E) F) G)

–80 mV +80 mV –66 mV +66 mV –10 mV -15mV +33mV -33mV

Example of single best answer: In the following question which one of the following statements is INCORRECT? 1) Glia cells A) Are found in small quantities in the brain B) Are important for water regulation using Aquaporin 4 C) Can form the structural support for neurones D) Can myelinate neurones E) Can be activated in response to brain tissue damage

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5BBL0213 Physiology and Pharmacology of the CNS Paper 2: Essay Paper (2/3 marks) Paper 2 is in two sections, section A and section B. You must choose one essay title from the choice of titles provided in section A and one essay title from section B. Use separate booklets for each of the two essays. You are recommended to spend 80 minutes on Paper 2 (40 minutes for each essay) which is worth 2/3 of the total marks for the examination (1/3 for each essay). Please ensure that your candidate number, desk number and the number of the question attempted are marked clearly on your answer booklets. Section A Answer one of the following three questions (1/3 total marks): The indicative answers give you a basic idea of the content required – similar to the detail in an essay plan. It is not by any means the whole answer, significantly more detail is required, however I hope it helps you understand what is being asked by the question. Note – there will obviously not be indicative answers in the real exam!  None of the questions will appear in the 2013 exams as they are worded here, but this does not mean that essay questions will not cover some of these areas. I hope this helps – Good Luck 

1) Describe the main characteristics and function of the two superfamilies of neurotransmitter transporters (60%). Explain how three drugs act on neurotransmitter transporters to elicit their effects on synaptic function (40%). Indicative Answer i) Plasma membrane reuptake transporters superfamily. High affinity transporters Located on pre-synaptic neuronal membrane and glia Two types a) Na+-Cl- dependent e.g. dopamine, serotonin, noradrenaline transporters b) Na+-K+ dependent e.g. excitatory amino acids (glutamate and aspartate) Important for terminating neurotransmission and recycling of neurotransmitter. ii) Vesicular transporter superfamily. Located neuronal vesicles. Four types (VMAT, VAchT, VGlutT, VIAAT), but all rely on H+-ATPase pump. Important for neurotransmitter storage preventing metabolism, neuronal leakage and toxicity Examples of drugs could be tiagabine, Prozac, amphetamines.

2) Why are secondary messengers necessary for the response to extracellular chemical signals? Describe, with examples, how the use of secondary messengers allows an amplification of cellular responses to extracellular signals. Indicative Answer  Extracellular signals generally hydrophilic, so can’t cross plasma membrane – require receptors

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Receptor molecules would have to be massive to carry signals throughout cell on their own Receptor activation: amplification though production of multiple secondary messenger molecules via G proteins (e.g. G S and adenylate cyclase / Gq and phospholipase C) Amplification by tyrosine kinase cascades (e.g. trkB – Grb2 – Sos – Ras – Raf – MEK –ERK1/2) Amplification through coupling to multiple signaling pathways (e.g. trkB can activate cascade above, PI-3-K and PLC / PLC -linked GPCRs release IP3 and increase internal [Ca2+], Ca2+-calmodulin complex can also stimulate adenylate cyclase to produce cAMP Amplification is more energetically efficient, as fewer molecules of extracellular signal need to be released to affect target cells

3) What can the cellular location of a receptor tell you about the likely chemical nature of the endogenous ligand that acts on it? Indicative answer • Receptors can be located on plasma membrane i. (most common, LGIC, GPCR, IER) ii. ligand does not cross membrane easily, hydrophilic, charged, polar, large. • Receptors on intracellular organelle membranes i. (e.g. InsP3R, RyR) usually activated by 2nd messengers, ii. ligand binding site is in the cytosol iii. ligands are hydrophilic, charged, polar, usually small. • Receptors in cytosol (DBR), i. ligand must cross the plasma membrane ii. must be lipophilic, uncharged, iii. usually steroids or fatty acids

Section B Answer one of the following three questions (1/3 total marks): 1) What does glutamate normally do at synapses, and how does it contribute to neurodegeneration in disease. Indicative answer o o o o o

Glutamate is an excitatory amino acid neurotransmitter Normal function is to depolarise post-synaptic terminal Glutamate receptor subtypes...ionotropic and metabotropic Calcium influx is a normal part of physiological response Action is terminated transporters taking it up into astrocytes

o o

Excitotoxicity is caused excessive glutamine within synaptic regions This can result from (a) excessive release (b) defective uptake or (c) reversal of transporters Over activation of receptors raises Calcium levels, calcium can then activate many toxic processes Examples of diseases where excitotoxicity is implicated Therapeutic opportunities

o o o

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2) Discuss our understanding of the cellular and molecular basis for learning and memory. Give examples of pharmacological studies that support these ideas? Indicative answer  Define LTP and describe it as enhancement of EPSP usually demonstrated in hippocampus but not exclusive to this area.  Enhanced EPSP is driven experimentally by high frequency (tetanic), repetitive stimulation of pre-synaptic neurone.  Mechanisms involved in induction of LTP o increased exocytosis of glutamate. o Enhanced AMPA receptor stimulation producing larger depolarisation in postsynaptic neurone to expel Mg from NMDA-R and open VGCCs. o Activation of mGlu to drive PKC-mediated phosphorylation of NMDA receptors o Enhanced Ca entry into post-syn neurone (via NMDA-R and VGCC) leads to activation of nNOS, release of NO, retrograde transmission to further enhance glu release.  Mechanisms in involved in Expression of LTP o Driven by elevated Calcium. Include production of growth factors to increase neural sprouting and plasticity. Increased production of AMPA receptors so increased post-syn density. Further CaMKII driven phosphorylation of AMPA-R so increased sensitivity. All lead to persistent enhancement of EPSP.  Experimental evidence of link between LTP and memory is ability of NMDA antagonists to block LTP in vitro (slice work) and to impair memory formation in vivo (e.g. Morris Water Maze). NMDA-R1 knockout mice show impaired memory. CaMKII point mutant mice with no autophosphorylation show impaired memory in Y maze. Arachidonic acid supplementation which drives AMPA receptor sensitisation via kinase phosphorylation also enhances memory formation in aged rats.

3) Briefly describe the clinical and pathological features of Alzheimer's disease and Parkinson's disease (30%). Compare and contrast the different pharmacological approaches used to treat these two neurodegenerative disease (70%). Indicative answer AD • Amnesia. (dysmnesia “bad memory”) • Aphasia. • Apraxia. • Agnosia. • Associated features.  Cerebral atrophy  Senile plaques  Neurofibrillary tangles  Neuron loss  Treatment  Enzyme inhibitors  Cholinesterase inhibitors  Receptor antagonists  NMDA receptor antagonists PD  Tremor, Rigidity, Bradykinesia, Postural Instability

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 Non-motor – hypotension, bladder, GI tract, Sleep, anxiety, depression, cognitive dysfunction etc  Pathology o Loss DA neurons in nigrostriatal pathway o Loss of cells in other brain nuclei eg raphe, LC, DMNV, NBM o Lewy bodies (Braak Hypothesis)  DA replacement therapy o Precursor – L-dopa o Agonist – DA agonists o Enzyme inhibitors – MAOI, COMTI, DDCI  Non-dopaminergic o Muscarinic antagonists o Antagonists – A2A antag, o NMDA antagonist - amantadine o Uptake inhibitors Both – nothing to reduce progression

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