dopamine and parkinsons Flashcards
Describe the production and regulation of dopamine
- Tyrosine enters neuron via active transport and is converted to LDOPA by tyrosine hydroxylase within the cytoplasm of dopaminergic neuron
- LDOPA converted to dopamina via DOPA-decarboxylase
- Dopamine actively transported into storeage vesicles by vesicular transport mechanisms
- When released into the synaptic cleft, it is actively transported back into neuronal termianl (reuptake 1) with 50% of this transported into vesicles for storeage and release
- The remainder of dopamine is broken down by monoamine oxidase
- Some dopamine is actively transported into effector cell (reuptake 2) where it is inactivated by Catchol-O-Methytransferase (COMT)
- Remaining dopamine diffuses into circulation
How is dopamine rmoved from circulation?
Destroyed by COMT and MAO in liver, producing alcohol and organic acids which are excreted into urine
What are the dopaminergic pathways and their functions?
- Nigrostriatal pathway (75%) - cell bodies lie insubstantia nigra and axons terminate in corpus striatum (origin or name) to function for motor control
- Mesocortical pathway - cell bodies lie in midbrai vertal tegmental area and project via the medial forebrain to frontal cortex to function for behavioural effects
- Mesolimbic pathway - cell bodies lie in midbrai vertal tegmental area and project via the medial forebrain to limbic system (especially nucleus accumbens and amygdalaid nucleus) to function for behavioural effects
- Tuberophyseal pathway - group of neurons running from ventral hypothalamus to median eminence of pituitary gland to regulate secretion of GH and prolactin
Which pathway is affected in PD and how?
Nigrostriatal pathway dies off
Which pathway is affected in Schizophrenia and how?
Increased activity in mesolimbic and mesocortical pathways
Where is dopamine found in the medulla and what effect does this have?
Chemoreceptor Trigger Zone - vomit response
Reason why dopamine drugs have nauseated side effects
Where are dopamine receptors found and what function do they have?
- D1 receptors - most abunant and widespread, mostly in limbic system, thalamus and hypothalams. Mediate effects in periphery such as renal vasodilation and increase myocardial contractility
- D5 receptors - much higher affinity and regulate dium excretion in the kidney
- D2 are also abundant and widespread, found in striatum, limbic system, thalamus, hypothalamus and pituitary. Also found in non-dopaminergic neurons
- D3 receptors are in limbic and not in striatum
- D4 are weakly expressed but seen in cortex and limbic system
Which dopamine receptor is involved in the renal excretion of sodium?
D5
Which dopamine receptor is involved in renal vasodilation?
D1
What is schizophrenia and how does is present?
Occurs as a result of increased activity in mesolimbic and mesocortical pathways, presenting with:
- Hallucinations
- delusions
- thought disorders
- social withdrawal
- reduced drive
- inability to feel pleasure
Complicated pathophysiology but involves environmental factors and chromosomal abnormalities of cerebral cortex
What is Parkinsons Disease?
Degenerative disorder of the basal ganglia (nigrostriatal dopamine pathway)
What are the 4 clinical features of PD?
- Tremor - only visible at rest due to struggle in initiating movement
- Bradykinesia - slowness in initiating movement - shuffling gait
- Rigidity - resistance to movement of flexors and extensors to full range of movement
- Postural instability - falls are common with this
What genetic mutations lead to Parkinsons?
Alpha-synuclein - found in Lewy Bodies
Parkin
List 3 non-genetic influences of PD
Antipsychotic drugs - block dopamine receptors
Auto-oxidation of chatecholamines
Post encephalitic syndrome
What is Wilsons disease and how can tests be used to differentiate with PD?
Excess copper accumulation in body
Ceruloplasmin (low in WD)
24 hoiur urine copper (high in WD)
