Chapter 39: Neurochemistry

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1

What constitutes the central nervous system (CNS)?

The brain and spinal cord.

2

What constitutes the peripheral nervous system (PNS)?

The nerves outside the dura.

3

What insulates the axons of nerves?

Myelin insulates the axons of nerves.

4

What two cell types are responsible for producing myelin?

The oligodendrocytes (in the CNS) and Schwann cells (in the PNS).

5

What is a demyelinating disease of the CNS?

Demyelination of the CNS occurs in multiple sclerosis.

6

What is a demyelinating disease of the PNS?

Demyelination of the PNS occurs in Guillain–Barré syndrome.

7

Why is term blood–brain barrier (BBB) is a slight misnomer?

Its permeability depends on the size of the molecule in question.

8

What are markers are released from damaged neurons in degenerative or inflammatory conditions?

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In degenerative or inflammatory conditions, pathologic proteins are released from damaged cells.

9

What are the six sources of cerebrospinal fluid (CSF)?

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  1. blood–brain barrier (one-third of the volume)
  2. blood–CSF barrier (almost the remaining two-thirds)
  3. dorsal root ganglia
  4. brain parenchyma
  5. circulating CSF cells (mainly lymphocytes)
  6. meninges (under pathologic condition)
10

What is the CSF produced by the blood–CSF barrier called?

It is termed choroidal fluid because it is principally provided by the choroid plexuses situated in the lateral ventricles.

11

What is useful marker protein to distinguish CSF rhinorrhea from local nasal secretions?

One characteristic and useful marker protein in the CSF is asialotransferrin, which is transferrin lacking sialic acid.

(In the systemic circulation, this absence of sialic acid gives a molecular signal for the protein to be recycled)

12

Three weeks after an acute diarrheal illness, a 65-year-old man presented with progressive ascending weakness of the limbs followed by respiratory muscle weakness requiring assisted ventilation.

  • He was hypotonic, had no reflexes and profound general weakness.
  • Isoelectric focusing of CSF showed abnormal oligoclonal bands.

What is the diagnosis?

This predominantly motor neuropathy is Guillain–Barré syndrome, and the patient has antibodies developed as a result of infection with the bacterium Campylobacter jejuni.

13

A 75-year-old woman complained of postural dizziness, dry mouth, intermittent diarrhea, and numbness in both of her feet.

  • Marked decrease in blood pressure on assuming upright posture.
  • A chest radiogram revealed lytic lesions in the sternum.
  • Her urine contained Bence–Jones protein.
  • Bone marrow examination showed increased plasma cells.

What is the diagnosis?

Her neurologic condition was caused by amyloidosis, in which the free light-chain component of myeloma globulin produced by a tumor of plasma cells in the bone marrow accumulates in peripheral nerves.

14

What are the three major types of glial cells in the central nervous system?

  1. astrocytes
  2. oligodendrocytes
  3. microglia
15

What three biological features of neurons are particularly worthy of note?

  1. their length
  2. their prolific interconnections
  3. they do not divide postpartum
16

What is axonal transport from the perikaryon toward the synapse called?

Anterograde transport provides packages of different proteins and mitochondria necessary for nerve terminal function.

17

What is axonal transport from the synapse towards the perikaryon called?

Retrograde transport removes impaired particles and transfers signaling peptides released from postsynaptic neurons.

18

What two molecular “motors” mediate axonal transport?

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The normal “resting” movement within the axon is mediated by kinesin in the case of anterograde transport and dynein in retrograde transport.

19

What is almost exclusively the energy substrate for the brain?

glucose

20

What is the role of astrocytes in response to injury to the CNS?

Astrocytes can play a major part in the reaction, synthesizing large amounts of glial fibrillary acidic protein (GFAP).

21

What neurodegernative condition is associated with GFAP?

This is the cellular equivalent of scar tissue and is found in diseases such as multiple sclerosis, in which it is the major constituent of the plaques.

22

What are the myelinating cells of the CNS?

The oligodendrocytes present in the CNS can wrap around multiple axons, forming the myelin sheath that insulates these neuronal processes.

23

What are the myelinating cells of the PNS?

In the PNS, the Schwann cells form the myelin and typically wrap around only a single axon.

24

What is the mechanism of metabotropic neurotransmitter receptors?

Binding of neurotransmitter activates a second messenger, such as a cyclic nucleotide, which may stimulate protein phosphorylation.

25

What is the mechanism of ionotropic neurotransmitter receptors?

Binding of neurotransmitter opens ion channels, resulting in its influx into postsynaptic cells evoking their depolarization (action potential).

26

What are the two general types of input that a neurotransmitter can provide?

The input of a particular neurotransmitter can essentially be classified as excitatory or inhibitory.

27

What enzyme catalyzes the synthesis of acetylcholine (ACh)?

Acetylcholine (ACh) is synthesized from acetyl-CoA and choline by choline acetyltransferase (ChAT).

28

What are the two classes of acetylcholine receptors?

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The effects demonstrated by nicotine are characteristic of nicotinic receptors, whereas those of muscarine characterize the muscarinic receptors.

29

What is the classic muscarinic antagonist?

The classic antagonist of the muscarinic effect is atropine.

30

What is the classic nicotinic antagonist?

The best-studied blocker for the nicotinic receptor is the poisonous snake venom α-bungarotoxin.

31

What enzyme provides acetyl-CoA for ACh synthesis?

ACh synthesis and the functional competence of cholinergic neurons strongly depend on the provision of acetyl-CoA by pyruvate dehydrogenase.

32

What are the two the most common neurodegenerative brain pathologies?

Vascular dementia and Alzheimer's disease (AD) are the most common neurodegenerative brain pathologies in aging human populations.

33

What structural proteins are a diagnostic marker for neurodegenerative brain pathologies?

Degenerating neurons release several structural proteins, including tau peptides.

34

What condition is caused by autoantibodies are formed against the nicotinic receptor?

In myasthenia gravis, autoantibodies are formed against the nicotinic receptor.

35

What condition is caused by thiamine pyrophosphate deficiency?

In Wernicke–Korsakoff encephalopathy, the activities of complexes of pyruvate dehydrogenase and ketoglutarate dehydrogenase are inhibited due to the deficit of their cofactor thiamine pyrophosphate

36

A 25-year old migrant worker was admitted to the hospital emergency unit with persistent vomiting, heavy diarrhea, edema, and loss of sensation in his legs.

  • His blood pressure was 60/40 mmHg.
  • He was hypothermic (33 C).
  • He had atrial fibrillation and severe edema.
  • Laboratory tests displayed severe lactic acidosis.

What is the diagnosis?

This condition most probably resulted thiamine deficiency from a frugal diet based on polished rice without supplementation with essential nutrients.

37

What amino acid are catecholamines synthesized from?

The catecholamines, epinephrine and norepinephrine, are syn­thesized from L-tyrosine.

38

What is the precursor of norepinephrine and epinephrine?

Dopamine is a precursor of norepinephrine and epinephrine.

39

What brain pathway is dopamine found in?

Dopamine is a transmitter in the dopaminergic neurons located in several brain areas, including the substantia nigra.

40

What CNS pathologies are associated with disturbances of dopamine metabolism? (3)

Disturbances of dopamine metabolism are associated with several CNS pathologies, including

  1. Parkinson's disease,
  2. schizophrenia, and
  3. restless legs syndrome.
41

What drug is used to treat disorders of dopamine deficiency?

To overcome dopamine deficits in some of these diseases, L-DOPA, its precursor, is administered because it easily crosses the blood–brain barrier.

42

What is an emergency indication for dopamine?

Dopamine is given to patients in shock and with heart failure to increase cardiac output, blood pressure, and renal filtration.

43

How do amphetamines, cocaine, and nicotine, exert their addictive effects?

Several drugs exert their behavioral and addictive effects through excessive stimulation of the release of dopamine in the synaptic cleft.

44

What two receptors mediate the actions of catecholamines?

Their actions are mediated through the α-adrenergic receptor, blocked by phentolamine, and β-adrenergic receptor, blocked by propranolol.

45

What two enzymes are responsible for degradation of catecholamines?

The action of catecholamines is terminated by their reuptake and degradation by mitochondrial monoamine oxidases and subsequent methylation by catechol-O-methyltransferase to homovanillic or vanillylmandelic acids.

46

What condition is associated with excess urinary homovanillic or vanillylmandelic acids?

Excess of these compounds in urine may indicate the presence of adrenal medullar tumor, pheochromocytoma.

47

What phenomenon involved in learning, memory formation, and other cognitive functions does glutamate play an important role in?

Glutamatergic receptor stimulation is subject to regulatory mechanisms that play an important role in synaptic plasticity, termed long-term potentiation.

48

What condition can be caused by excessive glutamate release?

Epilepsy is the pathologic condition caused by excessive glutamate release by pathologically stimulated glutamatergic neurons.

49

What is the chief inhibitory neurotransmitter in the brain?

GABA is the chief inhibitory neurotransmitter in the brain.

50

Which drugs exhert their effects through the GABA recepter?

The most common groups include

  1. barbiturates,
  2. benzodiazepines,
  3. chloral hydrate, and
  4. valproate.
51

What condition is caused by mutations of sodium channels?

Mutations of sodium channels can occur at different sites and give rise to hyperkalemic periodic paralysis.

52

What condition is caused by mutations of chloride channels?

The negative ion chloride moves through chloride channels, which are implicated in specific pathologic states, such as myotonia.

53

Which ions important role in the synchronization of neuronal activity?

Calcium ions have an important role in the synchronization of neuronal activity.

54

What condition is caused by mutations of calcium channels?

Within the CNS, Lambert–Eaton syndrome is a disease that affects predominantly the P/Q subtype of calcium channels.

55

What protein derived from anaerobic bacteria can be used theureputically to block presynaptic release of neurotransmitter?

Botulinum toxin, which contains enzymes to hydrolyze the presynaptic proteins involved in the release of neurotransmitters.

56

What is a theurputic indication of botulinum toxin?

This toxin is used in special cases of spasticity, such as torticollis, in which the patient can be relieved of the excessive contractures of the neck muscles.

57

An 18-year-old male awoke in the night with intense weakness of the proximal muscles of his arms and legs.

  • Serum potassium was reduced at 2.9 mmol/L (normal 3.5–5.3)
  • A further attack was induced by an infusion of intravenous glucose.

What is the diagnosis?

Hypokalemic periodic paralysis is inherited as a dominant trait and results from a mutation in the gene encoding the L-type calcium channel.

58

What are genetic diseases that affect ion-channel function called?

channelopathies

59

Twenty-four hours after eating home-preserved vegetables, a healthy young woman experienced the progressive onset of blurred vision, severe vomiting, dysphagia, and advancing limb weakness starting in the shoulders. What is the diagnosis?

The vegetables contained the exotoxin of the anaerobe Clostridium botulinum, which had not been destroyed during the preservation process.

60

Decribe the mechanism of vision. (8)

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  1. Cis-retinal is converted to trans-retinal.
  2. Rhodopsin becomes activated.
  3. The level of cGMP decreases.
  4. Na+ entry into the cell is blocked.
  5. The rod cell hyperpolarizes.
  6. There is release of glutamate (or aspartate).
  7. An action potential depolarizes the adjacent bipolar cell.
  8. An action potential is sent out of the eye.