Parkinson's Disease Flashcards
What is declarative memory?
Factual information.
Life events.
Available to consciousness.
Easily formed and forgotten.
What is non-declarative memory?
Procedural memory.
Motor skills.
Not available to consciousness.
Less easily formed, but harder to forget.
What is ballistic movement?
Movement based on pre-programmed instructions.
Rapid - but at the expense of accuracy.
What are Pursuit Visual feedback movements?
Motor command is continually updated according to sensory feedback (visual).
Highly accurate as can be modified in progress, but slow.
What is the function of the prefrontal cortex? Where is it located?
Makes the decision to make a movement.
Found at the front of the frontal lobe.
What is the function of the primary motor cortex? Where is it located?
Generates impulses to control the execution of movement.
In the frontal lobe in the precentral gyrus.
Motor homunculus.
What is the function of the supplementary and premotor cortex? Where are they located?
For planning movements.
Anterior to the primary motor cortex.
In a finger moving task, which areas of the brain would exhibit activity?
If just mentally rehearsing the movement, where would activity be seen?
SMA, M1 and S1.
SMA only.
Explain how sensory information is important for co-ordinated movement.
Proprioception: feedback from sensory receptors (muscle spindles) about the position and movements of limbs.
Vision: Eyes, visual system and visual cortex.
Vesibular: Feedback from organs of balance.
What is the main non-cortical structures involved in movement?
The basal ganglia.
What is the main input of the basal ganglia?
Prefrontal cortex.
What is the main output of the basal ganglia?
Pre-motor area via the thalamus.
What are the functions of the basal ganglia?
Grey matter nuclei deep beneath the cerebral cortex.
Initiation of movement by putting the motor plan into action.
Planning of complex voluntary movement.
Inhibit unwanted movments.
Posture and muscle tone.
What is the main input of the cerebellum?
Input from the sensory cortex.
What is the main output of the cerebellum?
Primary motor cortex via thalamus.
What are the functions of the cerebellum?
Coordination and smooth execution of movements.
Motor learning and error detection.
What are the lateral descending pathways for motor movement?
What is there function and location?
Corticospinal and ruberospinal tract.
Control voluntary movement e.g. fine movement of hand.
Run in the lateral funiculus.
What are the ventromedial descending pathways for motor control function? Where do they run?
Reticulospinal and vestibulospinal.
Control axial muscles and posture.
Run in the ventral funiculus.
What is a motor unit?
A motor neuron and all the fibres it innervates.
What makes up the striatum?
Caudate nucleus and lentiform nucleus.
What makes up the lentiform nucleus?
Putamen and Globus Pallidus.
What makes up the corpus striatum?
Caudate nucleus, putamen and globus pallidus.
Describe the pathway of the lateral descending motor pathways?
Prefrontal cortex Thalamus Basal Ganglia Thalamus Premotor Area 6 Primary Motor cortex 4 Spinal cord lateral funiculus - Ruberospinal and Corticospinal tracts.
Describe the pathway of ventromedial descending motor pathways?
Sensory cortex Cerebellum Thalamus Primary Motor cortex 4 Spinal cord in ventral funiculus as Reticulospinal and Vesibulospinal tracts.
Name the extra-pyramidal tracts.
Vestibulospinal, Reticulospinal, Rubrospinal and Tectospinal.
How is Dopamine synthesised?
Tyrosine enters the neuron via active transport.
In the cytoplasm, tyrosine is converted to DOPA via tyrosine hydroxylase.
DOPA is then converted to dopamine by DOPA de-carboxylase.
Dopamine is then actively transported into storage vesicles by the vesicular transport system.
How is dopamine released and what is its fate?
Dopamine is released to the synaptic cleft.
It is then either actively transported to the neurone terminal - reuptake 1.
FINISH
Name the 4 main dopaminergic pathways in the brain?
Nigrostriatal pathway
Mesolimbic pathway
Mesocortical pathway
Tuberohypophyseal System
Descibe the Nigrostriatal pathway?
Accounts for 75% of dopamine in the brain.
Cell bodies are mainly in the Substansia Nigra.
Axons terminat in the corpus striatum.
Fibres run in the medial forebrain bundle.
Describe the Mesolimbic pathway?
Cell bodies are in the midbrain ventral tegmental area adjacent to the substania nigra. Project via the medial forebrain bundle to parts of the limbic system (nucleus accumbens and the amygdaloid nucleus).
Describe the Mesocortical pathway?
Cell bodies lie in the VTA.
Project via the medial forebrain bundle to the frontal cortex.
Describe the Tuberhypophyseal System?
Groups of neurons run from the ventral hypothalamus to the median eminence and pituitary glands.
Acts to regulate prolactin secretion.
What dopamine receptors are in the D1 family? How do they work?
D1 and D5.
Activate adenylyl cyclase, increasing cAMP (second messenger).
What dopamine receptors are in the D2 family?
D2, D3 and D4.
Inhibits adenylyl cyclase, decreasing cAMP.
Where are D1 receptors found?
Most abundant and widespread.
Mainly striatum, limbic system, thalamus, hypothalamus.
Where are D2 receptors found?
striatum, limbic system, thalamus, hypothalamus and also the pituitary gland.
Where are D3 receptors found?
The limbic system.
NOT IN STRIATUM.
Where are D4 receptors found?
Weakly expressed in cortex and limbic systems.
What effects at the periphery do dopamine receptors mediate?
D1 receptors mediate renal vasodilation and increase myocardial contractility.
Name other monaminergic systems?
Noradrenergic System Seratonergic Pathways (5-HT).
Describe the Noradrenergic System?
Found in the Locus Coeruleus of the pons and project to many areas in the CNS such as the cortex, thalamus, hypothalamus, olfactory bulb, cerebellum and spinal cord.
Involved in regulating attention, arousal and sleep-cycles.
Also involved in learning and memory, anxiety and pain, mood and brain metabolism.
Describe Seratonergic pathways?
Found in the 9-raphe nuclei on either side of he midline of the brainstem.
Project to almost all parts of the CNS.
Caudally in the medulla they innervate the cord and modulate pain-related sensory signals.
How is Dopamine synthesised?
Tyrosine enters the neuron via active transport.
In the cytoplasm, tyrosine is converted to DOPA via tyrosine hydroxylase.
DOPA is then converted to dopamine by DOPA de-carboxylase.
Dopamine is then actively transported into storage vesicles by the vesicular transport system.
How is dopamine released and what is its fate?
Dopamine is released to the synaptic cleft.
It is then either actively transported to the neurone terminal - reuptake 1.
FINISH
Name the 4 main dopaminergic pathways in the brain?
Nigrostriatal pathway
Mesolimbic pathway
Mesocortical pathway
Tuberohypophyseal System
Descibe the Nigrostriatal pathway?
Accounts for 75% of dopamine in the brain.
Cell bodies are mainly in the Substansia Nigra.
Axons terminat in the corpus striatum.
Fibres run in the medial forebrain bundle.
Describe the Mesolimbic pathway?
Cell bodies are in the midbrain ventral tegmental area adjacent to the substania nigra. Project via the medial forebrain bundle to parts of the limbic system (nucleus accumbens and the amygdaloid nucleus).
Describe the Mesocortical pathway?
Cell bodies lie in the VTA.
Project via the medial forebrain bundle to the frontal cortex.
Describe the Tuberhypophyseal System?
Groups of neurons run from the ventral hypothalamus to the median eminence and pituitary glands.
Acts to regulate prolactin secretion.
What dopamine receptors are in the D1 family? How do they work?
D1 and D5.
Activate adenylyl cyclase, increasing cAMP (second messenger).
What dopamine receptors are in the D2 family?
D2, D3 and D4.
Inhibits adenylyl cyclase, decreasing cAMP.
Where are D1 receptors found?
Most abundant and widespread.
Mainly striatum, limbic system, thalamus, hypothalamus.
Where are D2 receptors found?
striatum, limbic system, thalamus, hypothalamus and also the pituitary gland.
Where are D3 receptors found?
The limbic system.
NOT IN STRIATUM.
Where are D4 receptors found?
Weakly expressed in cortex and limbic systems.
What effects at the periphery do dopamine receptors mediate?
D1 receptors mediate renal vasodilation and increase myocardial contractility.
Name other monaminergic systems?
Noradrenergic System Seratonergic Pathways (5-HT).
Describe the Noradrenergic System?
Found in the Locus Coeruleus of the pons and project to many areas in the CNS such as the cortex, thalamus, hypothalamus, olfactory bulb, cerebellum and spinal cord.
Involved in regulating attention, arousal and sleep-cycles.
Also involved in learning and memory, anxiety and pain, mood and brain metabolism.
Describe Seratonergic pathways?
Found in the 9-raphe nuclei on either side of he midline of the brainstem which fire more rapidly when awake.
Project to almost all parts of the CNS.
Caudally in the medulla they innervate the cord and modulate pain-related sensory signals.
Rosterally in the pons and medulla they innervate the brain for arousal.
What is Parkinson’s Disease?
A late-onset, degenerative disorder of the basal ganglia.
It is progressive.
Cause by degeneration of dopaminergic neurons and formation of fibraller cytoplasmic inclusions.
Describe causes of Parksinson’s?
Caused by a mix of environmental and genetic factors.
- Side effect of anti-psychotic drug therapies that block dopamine receptors.
- Toxic reaction to chemical agents e.g. MPTP.
- Severe CO poisoning.
- Genetics.
Describe the pathophysiology of Parkinson’s disease?
- Oxidative Stress: Auto-oxidation of catacholeamines my injure neurons due to oxidative metabolites. Neurons are unable to render the metabolites harmless.
- Genetics: Mutations in alpha-synuclein cause a rare, autosomal dominant form. Alpha-synuclein is a main component of Lewy bodies.
Mutations in the protein Parkin, is associated with an autosomal recessive early-onset form.
Describe the clinical manifestations of Parkinson’s?
Tremor: Mainly affecting distal regions. Usually unilateral at first. Usually present at rest but disappears during movement or sleep. Often a pill-rolling tremor.
Rigidity: Resistance to movement of flexors/extensors. Most evident during passive movement - usually a jerky cog-wheel movement. Unilateral at first but progresses bilaterally.
Bradykinesia: Slowness in initiating and performing movment with sudden stopping. Shuffling gait.
Postural Instability: Shuffling gait, reduced arm swing, altered centre of gravity leading to falls, stooped posture.
Speech/writing: Monotone, slow, slurred, uncoordinated due to loss of muscle control. Dribbling is common. Writing becomes worse.
Autonomic Symptoms: As basal ganglia can influence the ANS, can get excessive sweating, salivation and sebaceous gland secretion.
In late disease, lacrimation, dysphagia, thermal regulation, incontinence and impotence may occur.
Dementia: Due to degeneration also occurring in other areas of the brain e.g. the frontal cortex.
How is Parkinson’s diagnosed?
Usually through symptoms and neurological examination.
By seeing improvements after taking drugs.
What is the aim of Parkinson’s treatment?
To slow progression and manage symptoms.
Name types of Parkinson’s drugs?
L-dopa Carbidopa Monoamine Oxidase B Inhibitors COMT Inhibitors Dopamine Agonists
How does L-dopa work?
L-dopa is a precursor of dopamine which can cross the BBB. It is converted to dopamine in the brain. It enhances dopaminergic neurotransmission in the coprus striatum by enhancing dopamine synthesis in surviving neurons of the substansia nigra.
Over time neurons decrease and cells are unable to convert L-dopa to dopamine.
Why are large doses of L-dopa needed?
As most of the drug is decarboxylated at the periphery.
Why is Dopamine not used as a Parkinson’s drug?
As it cannot cross the blood-brain barrier.
How does Carbidopa work?
Carbidopa is a dopa-decarboxylase inhibitor, that cannot cross the BBB. Therefore it decreases levadopa metabolism at the periphery, increasing levodopa availability for the CNS.
It lowers the levodopa dose by 5-fold, decreasing side effects such as nausea and vomiting and altered BP.
Why would levodopa cause altered BP?
as L-dopa is converted to dopamine, which causes adrenaline/noardrenaline release.
How do monoamine oxidase B inhibitors work?
Reduce dopamine breakdown in the CNS, particularly at the corpus striatum. e.g. Selegilline.
How do COMT inhibitors work?
Prolong dopamine activity by preventing its breakdown by inhibiting the action of Catechol-O-methyl Transferase.
Describe how dopamine agonists work?
D2/3 receptor selective agonists e.g. Pramipexole.
A downside is it can act on other areas of the brain where dopamine is required.
Can cause hallucinations or compulsive behaviour (shopping, gambling).
Describe Deep brain stimulation?
Used to treat parkinsons.
Involves surgical implantation of high-frequency thalamic electrical stimulator that interrupts tremor-causing nerve impulses.
Helps minimise dystonia.
Can reduce the need for drugs.
