PARKINSONS1 Flashcards
What symptom involves increased muscle tone and rigidity?
Muscle rigidity, stiffness
What is a hallmark symptom characterized by shaking at rest?
Tremor at rest
What term describes a reduction in voluntary movement, slowness of movement, and difficulty initiating and stopping movements?
Hypokinesia, bradykinesia, motor activity difficult to initiate & stop
What function does the basal ganglia perform regarding sensory information?
Converts highly processed sensory information into motor program
What is the significance of the multiple circuits within the basal ganglia?
They are involved in various functions, including motor functions and non-motor functions like cognition, motivation, and addiction
What percentage of the population over 50 years is affected by Parkinson’s disease?
Affects 1% of the population over the age of 50 yrs
What is the primary cause of motor disturbances in Parkinson’s disease?
Loss of DAergic neurons in the nigrostriatal tract
What are the expected motor disturbances in Parkinson’s disease?
Hypokinesia - reduced spontaneous movement, leading to symptoms like slowness, stiffness, and difficulty initiating movement
What type of disorder is Huntington’s disease?
Progressive, inherited disorder
What neurotransmitter-producing neurons are lost in Huntington’s disease?
GABAergic neurons in striatum
What motor disturbances are expected in Huntington’s disease?
Hyperkinesia (jerky involuntary movement) and dementia - involuntary movements, cognitive decline, and psychiatric symptoms
What is the initial step in adrenaline synthesis?
Tyrosine Hydroxylation
Which enzyme catalyzes the conversion of tyrosine to L-DOPA?
Tyrosine hydroxylase
Where does the conversion of tyrosine to L-DOPA primarily occur?
In the cytoplasm of catecholamine-producing cells
What is the enzyme responsible for the decarboxylation of L-DOPA?
Aromatic L-amino acid decarboxylase (DOPA decarboxylase)
What is removed from L-DOPA during its decarboxylation to form dopamine?
Carboxyl group (-COOH)
What neurotransmitter is formed as a result of L-DOPA decarboxylation?
Dopamine
Which enzyme converts dopamine to norepinephrine?
Dopamine β-hydroxylase
Where does the conversion of dopamine to norepinephrine typically occur?
Within synaptic vesicles of nerve terminals in the sympathetic nervous system
What is the final step in adrenaline synthesis?
Conversion of Norepinephrine to Epinephrine
Where does the final step of adrenaline synthesis primarily occur?
In the adrenal medulla, located above the kidneys
Which enzyme catalyzes the conversion of norepinephrine to epinephrine?
Phenylethanolamine N-methyltransferase (PNMT)
What group is added to norepinephrine during its conversion to epinephrine?
Methyl group (-CH3)
What are the primary symptoms of Parkinson’s Disease (PD)?
Tremor at rest, Muscle rigidity, stiffness, Bradykinesia, motor activity difficult to initiate & stop
What was the first neurotransmitter associated with Parkinson’s Disease?
Dopamine (DA)
In which brain region are dopaminergic (DAergic) neurons lost in Parkinson’s Disease?
Substantia nigra
What is the characteristic pattern of walking observed in individuals with Parkinson’s Disease?
Parkinson’s disease gait
Describe Braak stages 1 & 2 of Parkinson’s Disease progression.
Characterized by early degeneration and disturbances in sleep and olfaction
Describe Braak stages 3 & 4 of Parkinson’s Disease progression.
50-80% of nigrostriatal neurons are lost, and motor symptoms start to emerge
Describe Braak stages 5 & 6 of Parkinson’s Disease progression.
Lewy bodies become prominent, and psychiatric symptoms, including dementia, may emerge. Compensation by D1 and D2 receptors also occurs.
What impact can Parkinson’s disease gait disturbances have on a person’s mobility?
Significantly impact mobility and quality of life in advanced stages of the disease
What neurotransmitter systems are significantly altered in Parkinson’s Disease (PD)?
Dopamine (DA) and gamma-aminobutyric acid (GABA)
In a healthy brain, what is the role of dopamine in relation to GABAergic neurons?
Dopamine inhibits GABAergic neurons originating from the substantia nigra, allowing for smooth transmission of signals from the thalamus to cortical areas
How does the loss of dopaminergic neurons in PD affect GABAergic activity?
Decreased dopamine levels result in overactivity of GABAergic inhibitory neurons
What is the consequence of overactive GABAergic neurons in PD?
Inhibition of the thalamic relay, causing difficulty in initiating and stopping movements, such as bradykinesia and akinesia
Besides dopamine and GABA, what other neurotransmitter imbalances are observed in PD?
Acetylcholine (ACh), noradrenaline (NA), serotonin (5-HT), and further disturbances in GABAergic transmission
What motor symptoms are associated with hyperactivity of cholinergic neurons in PD?
Tremor and rigidity
What is bradykinesia, and what causes it in Parkinson’s Disease (PD)?
Bradykinesia involves a reduction in the speed and frequency of voluntary movements, caused by the loss of inhibition of GABAergic cells by dopamine.
How does increased activity of GABAergic neurons in the globus pallidus contribute to bradykinesia?
It inhibits cortical areas responsible for initiating movements, resulting in difficulty initiating movements.
What are the hallmark motor features of Parkinson’s Disease (PD)?
Tremor and rigidity
What neurotransmitter systems are involved in the manifestation of tremor and rigidity in PD?
Acetylcholine, noradrenaline, serotonin, and gamma-aminobutyric acid (GABA)
How does dopamine inhibition affect cholinergic interneurons in the striatum, and what is the consequence?
Dopamine inhibition strongly suppresses cholinergic interneurons, resulting in their hyperactivity, associated with tremor and bradykinesia.
What is the key aspect of neurochemical changes in PD related to motor symptoms?
The imbalance between dopamine and acetylcholine (DA/ACh imbalance)
What psychiatric symptoms can manifest in later stages of PD?
Depression, anxiety, and cognitive impairment
Besides dopaminergic dysfunction, what other factors contribute to the development of psychiatric symptoms in PD?
Alterations in other neurotransmitter systems and neural circuits
What are some factors contributing to the higher incidence of Parkinson’s Disease in rural areas compared to urban regions?
Pesticide exposure, Genetic links, Oxidative stress and neuroinflammation, Drug-induced PD
How do pesticides like rotenone contribute to the development of Parkinson’s Disease?
They selectively inhibit mitochondrial function, inducing Parkinson’s Disease in animal models
What genetic mutations have been associated with the development of Parkinson’s Disease?
Mutations of α-synuclein, Mutation in the parkin gene, Mutations of mitochondrial proteins
What role do oxidative stress and neuroinflammation play in Parkinson’s Disease?
They contribute to the development and progression of the disease
Which medications can induce Parkinson’s-like symptoms as side effects?
Antipsychotics, Lithium, valproate (antiepileptic), Some antiemetics
What specific neurotoxin has been linked to the development of Parkinson’s Disease in some cases?
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
How does MPTP contribute to the development of Parkinson’s Disease-like symptoms?
It is metabolized to MPP+ in the brain, damaging dopamine-producing neurons
What is the role of oxidative stress and inflammation in the pathogenesis of Parkinson’s Disease?
They damage neurons and trigger neurodegenerative cascades, contributing to disease progression
