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Neuroanatomy Exam 1 > Biochemistry - Dopamine > Flashcards

Biochemistry - Dopamine Flashcards

1
Q

What is MPPP and why was it taken?

A

MPPP was an opiate analog essentially mimicking Meperidine (demerol). Addicts would take it for a high.

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2
Q

What is MPTP and what did it cause?

A
  • MPTP was the downstream product of MPPP that was essentially causing the Parkinsonism symptoms. The substantia nigra pars compacta cells (dopamine producers) were missing as a result.
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3
Q

Why is MPTP so toxic?

A
  • MPTP can cross the BBB, and once across it gets oxidized by the enzyme MAO to MPP+ that is taken up by dopamine cells. MPP+ is a site I mitochondrial toxin that is more toxic to dopamine cells because it concentrates there.
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4
Q

What are the two sites of inhibition of the progression of Parkinson Syndrome due to MPTP damage and what drugs act at each?

A

1) The Mao enzyme can be inhibited by Deprenyl which is a MAO inhibitor.
2) There is blockage of uptake of MPP+ at the pre-synaptic terminal- Mazindol works here.

  • Both have at least some protection against future progression of parkinson’s Syndrome .
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5
Q

What 4 clinical characteristics of Parkinson’s Disease?

A
  • Tremors
  • Bradykinesia ( slowness and poverty of movement, shuffling gait)
  • Rigidity
  • Postural instability
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6
Q

What are Lewy bodies and what do they indicate?

A

Lewy bodies are eosinophilic inclusion bodies filled with neurofilaments, glycoproteins, ubiquitin, and alpha-synuclein.

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7
Q

What diagnostic tracer is shown with a PET scan indicating its uptake at the substantia nigra thereby implying a loss of substantia nigra cells?

A

6-fluoro-dopa

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8
Q

Is Parkinson’s disease commonly bilateral?

What disease commonly coexists with Parkinson’s?

A
  • no it is commonly asymmetrical.

- Alzheimer’s disease.

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9
Q

What type of biochemical classification is dopamine?

A
  • Biogenic amine
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10
Q

What is the biggest area producing dopamine?

A

Substantia nigra pars compacta in the midbrain

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11
Q

What are the target area of Dopamine?

A

-Striatum, limbic cortex, amygdala, nucleus accumbens, prefrontal cortex

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12
Q

What are the functions of dopamine?

A

Movements, initiative, working memory

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13
Q

What dopamine pathway does Parkinson’s disease effect?

A
  • Mesostriatal (nigrostriatal) effecting dopamine delivery to the Striatum (Putamen and the Caudate. The nigrostriatal area is responsible for movement initiation.
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14
Q

What dopamine pathway does Schizophrenia effect?

A

Schizophrenia is due to the over-activation of the mesolimbic system. This mesolimbic cortical dementia is due to destruction of cells in this pathway, causing the overproduction of dopamine from the Ventral tegmental Area effecting the Mesolimbic pathway that causes resulting symptoms in the Cingulate cortex and the Nucleus accumbens.

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15
Q

What effets are manifested in the mesocortical pathway in Parkinson’s and Schizophrenia?

A

The mesocortical pathway is responsible for working memory and attention and motor initiation. Patients present with cognitive aspects in Parkinson’s and the negative symptoms in schizophrenia. Both of these are manifest in the prefrontal cortex.

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16
Q

What are some of the ultrashort projections of the local dopamine circuits in the brain?

A

1) Retina - between the inner and outer plexiform layers

2) Olfactory bulbs -

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17
Q

What are some intermediate-length projection local dopamine circuits in the brain?

A

1) Hypothalamus -

2) Medulla -

18
Q

What percentage of cells due we begin to loose per decade after age 25?
- At what percentage loss do we begin to start showing symptoms?

A

13%

80-90%

19
Q

What is the dopamine synthesis pathway?

A
  • Starting with phenyalanine (a.a.) –> L-Tyrosine (tyrosine hydroxylase) –> L-Dopa–>(dopa decarboxylase) –>Dopamine
20
Q

What is the most common treatment of Parkinson Syndrome?

A

Application of L-Dopa and Carbidopa. Carbidopa prevents conversion of L-Dopa to dopamine outside the brain, because Carbidopa can’t cross the BBB. Once past the BBB L-Dopa interacts with dopa decarboxylase.

21
Q

What types of pumps are necessary in a neurotransmitter uptake in a vesicle?

A
  • The Neurotransmitter is taken up by an H+/NT antiporter. The protons are pushed in from the acidic inner environment out, that is maintained by an ATPase proton pump.
22
Q

What drugs block a dopamine vesicle transporters?

A
  • Reserpine blocks the uptake of Dopamine possibly resulting in Parkinsonian symptoms.
23
Q

What type of transporter is on the presynaptic terminal ensuring that dopamine can be reused and is not needed to be generated as much?

A
  • A secondary active transporter- symporter that transports Sodium and dopamine into the cell.
24
Q

What is the major dopamine breakdown pathway?

A
  • Dopamine –> (MAO-B) –> DOPAL –> (Aldehyde dehydrogenase)–> DOPAC –> (Catechol-o-methyl transferase) –> HVA
  • HVA can show up in the urine as a dopamine turnover marker
25
Q

What type of drug has some effectiveness in treating Parkinson’s disease in the Dopamine breakdown pathway?

A
  • MAO-I block the MAO-B enzyme thereby increasing Dopamine levels.
26
Q

What drugs block the degradation of dopamine?

A
  • Deprenyl (MAO-I)
  • Selegiline (MAO-I)
  • Tolcapone (COMT-I)
  • Entacapone (COMT-I)
27
Q

What drugs act as dopamine receptor agonist?

A
  • Bromocriptine
28
Q

What drugs induce parkinson-like symptoms?

A
  • Reserpine (inhibits dopamine storage)
  • Typical antipsychotic (dopamine receptor antagonists)
    • -> Chlorpromazine
    • -> Loxapine
    • -> Haloperidol
29
Q

What is a main side effect of L-Dopa?

A
  • Hallucinations
30
Q

How do Amphetamines effect Dopamine processing?

A

Amphetamines increase dopamine release

31
Q

How do cocaine and tri-cyclic antidepressants effect dopamine release?

A

Cocaine and tri-cyclic antidepressants block reuptake of dopamine release.

32
Q

What are the common types of Parkinsonisms?

A
  • Ideopathic Parkinson’s disease
  • Genetic Parkinson’s disease
  • Toxin-induced parkinsonism
  • Drug-induced parkinsonism
  • Postencephalitic parkinsonism (Von Economo’s encephalitis)
  • Maganese toxins
33
Q

What are the G proteins in excitatory and inhibitory Dopamine receptors?

A

Gas -excitatory- increases cAMP

Gai - inhibitory - decreases cAMP

34
Q

What type of dopamine fibers does the striatum have?

A

The substantial nigra pars compacta projects dopamine releasing fibers via the nigrostriatial tract to the striatum ( caudate and putamen). The striatum has both excitatory and inhibitory receptors.

35
Q

What is unique about dopamine levels in the dopamine - acetyl choline balance?

A
  • If dopamine levels drop and acetyl choline levels stay the same, this is similar to having too much ACh. In reverse then, anticholinergics have some usefulness in treating Parkinson’s Disease.
36
Q

How can Dopamine act as both an excitatory or inhibitory activator at the Striatum and both result in stimulated activation?

A

Via different pathways. Dopamine can act as a stimulant at the Striatum in the “Direct Pathway” that activates and inhibitor of an inhibitor thereby activating. In the “Indirect pathway” Dopamine inhibits an inhibitor that would inhibit the subthalamic nucleus, thereby increasing acitivty

37
Q

What are the possible causes of Parkinson’s Disease?

A

1) Genetics
2) Environmental Toxins (Paraquat - weed killer, and Maganese)
3) L-DOPA therapy might increase progression of the disease

38
Q

What are some of the need to know clinical correlations of the following disorders:

  • Parkinson’s:
  • Schizophrenia
  • Cocaine:
  • Amphetamine:
  • L-Dopa:
  • Carbidopa:
  • Bromocriptine:
A 
Parkinson's: decre. dopamine
Schizophrenia: incre. dopamine
Cocaine: DA reuptake inhibitor
Amphetamine: DA release enhancer 
L-Dopa: DA precursor
Carbidopa: dopadecarboxylase inhibitor
Bromocriptine: DA receptor agonist
39
Q

What are some positive and negative symptoms of schizophrenia?

A
  • positive symptoms: hallucinations, delusions, bizarre behavior
  • Negative symptoms: social withdrawal, emotional blunting
40
Q

What are some causes of schizophrenic defects?

A
  • Genetics - 39% if both parents parents are effected
  • Structural abnormalities in the medial temporal lobe (altered orientation of hippocampal pyramidal cells which affects the molecules inovlved in cell migration and adhesion, enlarged ventricles
41
Q

What factor could dopamine play in Schizophrenia?

- What types of medications could be used if this is a cause?

A
  • Hyerdopaminergia of the mesolimbic system , excess activation of D2 receptors. Actually very supported due to elevated numbers of dopamine receptors in brain tissues.
  • D2 inhibitors - typical anti-psychotics.

Neuroanatomy Exam 1 (4 decks)

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