PARKINSONS1 Flashcards

1
Q

What symptom involves increased muscle tone and rigidity?

A

Muscle rigidity, stiffness

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2
Q

What is a hallmark symptom characterized by shaking at rest?

A

Tremor at rest

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3
Q

What term describes a reduction in voluntary movement, slowness of movement, and difficulty initiating and stopping movements?

A

Hypokinesia, bradykinesia, motor activity difficult to initiate & stop

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4
Q

What function does the basal ganglia perform regarding sensory information?

A

Converts highly processed sensory information into motor program

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5
Q

What is the significance of the multiple circuits within the basal ganglia?

A

They are involved in various functions, including motor functions and non-motor functions like cognition, motivation, and addiction

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6
Q

What percentage of the population over 50 years is affected by Parkinson’s disease?

A

Affects 1% of the population over the age of 50 yrs

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7
Q

What is the primary cause of motor disturbances in Parkinson’s disease?

A

Loss of DAergic neurons in the nigrostriatal tract

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8
Q

What are the expected motor disturbances in Parkinson’s disease?

A

Hypokinesia - reduced spontaneous movement, leading to symptoms like slowness, stiffness, and difficulty initiating movement

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9
Q

What type of disorder is Huntington’s disease?

A

Progressive, inherited disorder

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10
Q

What neurotransmitter-producing neurons are lost in Huntington’s disease?

A

GABAergic neurons in striatum

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11
Q

What motor disturbances are expected in Huntington’s disease?

A

Hyperkinesia (jerky involuntary movement) and dementia - involuntary movements, cognitive decline, and psychiatric symptoms

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12
Q

What is the initial step in adrenaline synthesis?

A

Tyrosine Hydroxylation

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13
Q

Which enzyme catalyzes the conversion of tyrosine to L-DOPA?

A

Tyrosine hydroxylase

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14
Q

Where does the conversion of tyrosine to L-DOPA primarily occur?

A

In the cytoplasm of catecholamine-producing cells

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15
Q

What is the enzyme responsible for the decarboxylation of L-DOPA?

A

Aromatic L-amino acid decarboxylase (DOPA decarboxylase)

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16
Q

What is removed from L-DOPA during its decarboxylation to form dopamine?

A

Carboxyl group (-COOH)

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17
Q

What neurotransmitter is formed as a result of L-DOPA decarboxylation?

A

Dopamine

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18
Q

Which enzyme converts dopamine to norepinephrine?

A

Dopamine β-hydroxylase

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19
Q

Where does the conversion of dopamine to norepinephrine typically occur?

A

Within synaptic vesicles of nerve terminals in the sympathetic nervous system

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20
Q

What is the final step in adrenaline synthesis?

A

Conversion of Norepinephrine to Epinephrine

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21
Q

Where does the final step of adrenaline synthesis primarily occur?

A

In the adrenal medulla, located above the kidneys

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22
Q

Which enzyme catalyzes the conversion of norepinephrine to epinephrine?

A

Phenylethanolamine N-methyltransferase (PNMT)

23
Q

What group is added to norepinephrine during its conversion to epinephrine?

A

Methyl group (-CH3)

24
Q

What are the primary symptoms of Parkinson’s Disease (PD)?

A

Tremor at rest, Muscle rigidity, stiffness, Bradykinesia, motor activity difficult to initiate & stop

25
Q

What was the first neurotransmitter associated with Parkinson’s Disease?

A

Dopamine (DA)

26
Q

In which brain region are dopaminergic (DAergic) neurons lost in Parkinson’s Disease?

A

Substantia nigra

27
Q

What is the characteristic pattern of walking observed in individuals with Parkinson’s Disease?

A

Parkinson’s disease gait

28
Q

Describe Braak stages 1 & 2 of Parkinson’s Disease progression.

A

Characterized by early degeneration and disturbances in sleep and olfaction

29
Q

Describe Braak stages 3 & 4 of Parkinson’s Disease progression.

A

50-80% of nigrostriatal neurons are lost, and motor symptoms start to emerge

30
Q

Describe Braak stages 5 & 6 of Parkinson’s Disease progression.

A

Lewy bodies become prominent, and psychiatric symptoms, including dementia, may emerge. Compensation by D1 and D2 receptors also occurs.

31
Q

What impact can Parkinson’s disease gait disturbances have on a person’s mobility?

A

Significantly impact mobility and quality of life in advanced stages of the disease

32
Q

What neurotransmitter systems are significantly altered in Parkinson’s Disease (PD)?

A

Dopamine (DA) and gamma-aminobutyric acid (GABA)

33
Q

In a healthy brain, what is the role of dopamine in relation to GABAergic neurons?

A

Dopamine inhibits GABAergic neurons originating from the substantia nigra, allowing for smooth transmission of signals from the thalamus to cortical areas

34
Q

How does the loss of dopaminergic neurons in PD affect GABAergic activity?

A

Decreased dopamine levels result in overactivity of GABAergic inhibitory neurons

35
Q

What is the consequence of overactive GABAergic neurons in PD?

A

Inhibition of the thalamic relay, causing difficulty in initiating and stopping movements, such as bradykinesia and akinesia

36
Q

Besides dopamine and GABA, what other neurotransmitter imbalances are observed in PD?

A

Acetylcholine (ACh), noradrenaline (NA), serotonin (5-HT), and further disturbances in GABAergic transmission

37
Q

What motor symptoms are associated with hyperactivity of cholinergic neurons in PD?

A

Tremor and rigidity

38
Q

What is bradykinesia, and what causes it in Parkinson’s Disease (PD)?

A

Bradykinesia involves a reduction in the speed and frequency of voluntary movements, caused by the loss of inhibition of GABAergic cells by dopamine.

39
Q

How does increased activity of GABAergic neurons in the globus pallidus contribute to bradykinesia?

A

It inhibits cortical areas responsible for initiating movements, resulting in difficulty initiating movements.

40
Q

What are the hallmark motor features of Parkinson’s Disease (PD)?

A

Tremor and rigidity

41
Q

What neurotransmitter systems are involved in the manifestation of tremor and rigidity in PD?

A

Acetylcholine, noradrenaline, serotonin, and gamma-aminobutyric acid (GABA)

42
Q

How does dopamine inhibition affect cholinergic interneurons in the striatum, and what is the consequence?

A

Dopamine inhibition strongly suppresses cholinergic interneurons, resulting in their hyperactivity, associated with tremor and bradykinesia.

43
Q

What is the key aspect of neurochemical changes in PD related to motor symptoms?

A

The imbalance between dopamine and acetylcholine (DA/ACh imbalance)

44
Q

What psychiatric symptoms can manifest in later stages of PD?

A

Depression, anxiety, and cognitive impairment

45
Q

Besides dopaminergic dysfunction, what other factors contribute to the development of psychiatric symptoms in PD?

A

Alterations in other neurotransmitter systems and neural circuits

46
Q

What are some factors contributing to the higher incidence of Parkinson’s Disease in rural areas compared to urban regions?

A

Pesticide exposure, Genetic links, Oxidative stress and neuroinflammation, Drug-induced PD

47
Q

How do pesticides like rotenone contribute to the development of Parkinson’s Disease?

A

They selectively inhibit mitochondrial function, inducing Parkinson’s Disease in animal models

48
Q

What genetic mutations have been associated with the development of Parkinson’s Disease?

A

Mutations of α-synuclein, Mutation in the parkin gene, Mutations of mitochondrial proteins

49
Q

What role do oxidative stress and neuroinflammation play in Parkinson’s Disease?

A

They contribute to the development and progression of the disease

50
Q

Which medications can induce Parkinson’s-like symptoms as side effects?

A

Antipsychotics, Lithium, valproate (antiepileptic), Some antiemetics

51
Q

What specific neurotoxin has been linked to the development of Parkinson’s Disease in some cases?

A

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)

52
Q

How does MPTP contribute to the development of Parkinson’s Disease-like symptoms?

A

It is metabolized to MPP+ in the brain, damaging dopamine-producing neurons

53
Q

What is the role of oxidative stress and inflammation in the pathogenesis of Parkinson’s Disease?

A

They damage neurons and trigger neurodegenerative cascades, contributing to disease progression