Week 8 - Neurodegenerative Disorders Part 2 Flashcards
(31 cards)
what is parkinson’s disease
multisystem neurodegenerative disorder = brain disorder that causes unintended or uncontrollable movements, such as shaking, stiffness and difficulty with balance and coordination
- Progressive degenerative disease producing abnormal movements known as Parkinsonism
- Age of onset usually from 50-75 but can affect younger people
what are the characteristics of parkinson’s
- Resting muscle tremors – shaking when your not doing anything
- Muscle stiffness (rigidity)
- Slow and decreased movement (bradykinesia/hypokinesia)
- Eventually gait and/or postural instability
What is bradykinesia
slow speed of movement
what is hypokinesia
movement disorder - smaller range of movement
what is dystonia
involuntary muscle contractions, abnormal postures, repetitive movements
what are the motor symptoms of Parkinson’s
- Bradykinesia
- Vocal symptoms
- Rigidity and postural instability
- Tremors
- Walking or gait difficulties
- Dystonia (involuntary muscle contractions)
- Difficulty swallowing, chewing and speaking
What are the non motor skill symptoms of parkinson’s
- Depression, anxiety, cognitive impairment
- Sense of smell loss
- Sweating and melanoma
- Gastrointestinal symptoms (constipation, drooling, faecal incontinence)
- Joint pain
What is the gait and progression of someone with Parkinson’s
tendency to lean forward, small, quick steps and reduced swinging of arms
what is the basal ganglia/nuclei and it importance for motor function
set of brain structures in telencephalon, diencephalon and mesencephalon
The basal ganglia are not directly responsible for initiating movement, but they are key in regulating and refining movement. They help ensure movements are:
Smooth, Coordinated, Appropriate in force and timing
- Damage to this area disrupts the dopamine pathways needed for smooth, controlled movement
- In parkinsons disease there’s less dopamine causes the basal ganglia circuit to become imbalance causing tremors, muscle rigidity ect..
What is the nigrostriatal pathway
- one of the major dopaminergic pathways in the brain
- neural pathway that connects the substantia nigra to the striatum
- uses dopamine as its primary neurotransmitter
- initiating and regulating voluntary movements
- modulates the direct and indirect pathways of the basal ganglia
What does the nigrostriatal pathway connect
substantia nigra to the striatum
What is the direct pathway
The direct pathway reduces inhibition on the thalamus, allowing it to stimulate the motor cortex → movement is initiated.
- using dopamine as neural transmitter
What is the indirect pathway
- the inhibition of the indirect pathway from dopamine increases inhibition on the thalamus, suppressing movement
What is the main neurotransmitter in the nigrostriatal pathway
dopamine - is what stimulate direct pathway and inhibits the indirect pathway
What are the neurochemical changes in parkinson’s
- low dopamine levels in the substantia nigra (less than 10% of normal)
- associated with loss of dopaminergic neurons in substantia nigra and degeneration of their nerve terminals in the striatum
- Loss balance between direct and indirect pathways – tipped in flavour of indirect pathway
what do low dopamine levels lead to
- Dopamine deficiency mostly related to hypokinesia/bradykinesia (slow movement, decreased movement, lack of movement) seen in Parkinson’s
is rigid muscles and tremors caused by low dopamine levels
No,
due to more complex disturbance of other neurotransmitters, including Ach, noradrenaline, serotonin and GABA, in addition to dopamine
- Ach release normally inhibited by dopamine, excessive Ach likely contributes to interrupted information transfer
what is excitotoxicity
neuronal injury or death caused by excessive stimulation by excitatory neurotransmitters, especially glutamate
what is glutamate
Glutamate is the main excitatory neurotransmitter in the brain and is essential for learning and memory. However, in large or prolonged amounts it becomes toxic to neurons – especially when it overstimulates glutamate receptors.
What happens to glutamate in a patient with parkinson’s
In Parkinson’s patients when the dopaminergic neurons degenerate it alters the balance between excitatory (glutamate) and inhibitory signals in the basal ganglia. The loss of dopamine removes inhibition of glutamate releasing neurons causing glutamate activity to increase. It results in excess glutamate to over stimulate neurons leading to excitotoxicity.
What occurs due to the overstimulation of neuronal glutamate receptors (NMDAR)
- results in neuronal calcium overload (NMDAR allows calcium influx) - calcium is a key player in glutamate neurotoxicity
- oxidative stress and neuronal self digestion
- mitochondrial damage - impaired ATP production
what is the impact of protein misfolding on neurodegenerative disorders
The aggregation of these misfolded proteins accumulation is toxic and can disrupt brain cell function leading to neurodegeneration (progressive brain damage and loss of function) resulting in diseases including Alzheimers and Parkinsons
what protein is misfolded in parkinson’s
Alpha synuclein - form toxic aggregates which:
- Build up inside neurons
- Disrupt normal cell function
- Lead to neuron death, especially in the substantia nigra a brain area that controls movement
What are drug treatments for Parkinson’s Disease
Current drugs used not treating underlying neurodegeneration but try and correct neurotransmitter imbalances e.g.
- Leyodopa – dopamine precursor used with carbidopa
- Bromocriptine – dopamine agonist
- Selegiline – decreased dopamine degradation
- Amantidine – enhanced dopamine release
Medicines can help treat the symptoms of Parkinson’s by:
- Increasing the level of dopamine in the brain
- Affecting other neurotransmitters
- Helping control non movement symptoms
