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Phar 303 > Neurotoxicology > Flashcards

Neurotoxicology Flashcards

1
Q

True/False? Neurotoxicants aren’t that effective at killing something

A

FALSE

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2
Q

Most toxins from living organisms are ____-toxic?

A

Neurotoxic

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3
Q

True/False? Computers contain neurotoxicants

A

True

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4
Q

What are the limitations to testing neurotoxicity on animals?

A

Can’t measure eg a mouse’s emoitons/cognitive behaviour

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5
Q

Is growing neurons in culture a good way to test in vitro toxicology? What can it measure? (2)

A

Yes, can measure outgrowth and firing rate

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6
Q

What are the four neuoroxic effects?

A 
Cognitive
Motor
Sensory
Mood/personality
General
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7
Q

What are examples of Cognitive neurotoxic effects?

A

Memory, learning, confusion

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8
Q

What are examples of Motor neurotoxic effects?

A

Weakness, convulsion, paralysis

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9
Q

What are examples of Sensory neurotoxic effects?

A

Vision, hearing, touch, balance

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10
Q

What are examples of Mood/Personality neurotoxic effects?

A

Sleep, depression, irritability, excitability

HARD TO TEST

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11
Q

What re examples of General neurotoxic effects?

A

Loos of appetite, fatigue

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12
Q

Neurons have a high energy requirement dependent on aerobic glycolysis. What is the consequence of this?

A

Anything that alters blood/O2 flow will greatly affect neurons

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13
Q

What are properties of the brain that affect neurotoxicity? (3)

A
  • Don’t have many enzymes to metabolize xenobiotics (any alien particle that reaches brain is pretty much stuck there)
  • High lipid content (50% myelin) so lipophillic toxins can get through BBB and latch onto myelin
  • Largest cells in body, High E content
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14
Q

Define anterograde and retrograde transport along axonal microtubules

A

Anterograde: From cell body to axon terminal
Retrograde: reverse, from axon terminal to cell body

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15
Q

How can toxins affect neurons? (4)

A

Can kill the neuron itself
Can cut the axon (through chemical/physical damage)*
Can damage the myelin sheath*
Can damage transmission of AP

*Damage can be temporary if schwann cells/oligodendrocytes are intact

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16
Q

True/False? Neurons can regenerate (if a toxin damages a neuron, it can regrow/be replaced)

A

False, brain damage is permanent

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17
Q

How much brain damage is necessary to be fatal?

A

Depends on where the damage occurs

e.g. breathing center is very small

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18
Q

Can you extrapolate data from animals to humans?

A

Yes but it’s hard

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19
Q

What property of the brain can mask toxicity for many years?

A

Neuronal plasticity - if you’re exposed to low levels of toxin chronically, brain can reconfigure to compensate

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20
Q

What happens during fetal exposure of neurotoxins?

A

Nonreversible tolerand and chemical imprinting

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21
Q

What are the 3 components of the Nervous system?

A

Central nervous system (Brain/Spinal chord)
Peripheral Nervous System
Autonomic Nervous System

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22
Q

What is an example of generalized neuronal damage?

A

Cerebral atrophy

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23
Q

What is a critical property of neurons? Why is that a problem?

A

Extremely specialized functions - vulnerable

If any one step gets disrupted, serious trouble

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24
Q

What are the 3 types of cells found in the brain?

A

Neurons
Glia
Capillaries

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25
Q

What are oligodendrocytes?

A

Provide myelination in CNS

One oligodendrocyte has many projections which wrap around axon

26
Q

What is a Schwann cell?

A

Provide Myelination in PNS

One schwann cells at a time wraps around axon

27
Q

What are microglia?

A

Variant of macrophage in CNS, many receptors to detect foreign bodies
Can stimulate local inflammation

28
Q

Describe the properties of the Blood Brain Barrier (2)

A

Designed to keep out foreign compounds
Reinforced version of a capillary
Has pumps to let vital things through

29
Q

How can a drug get into the CSF?

A

Has to cross:
Endothelial cell wall
Astrocyte
Pericytes

30
Q

True/False? Most things cannot get through the BBB

A

True

31
Q

True/False? Water and lipids cross the BBB through the same mechanism

A

True BUT
Water diffuses through tight junctions
Lipids/lipid soluble agents diffuse through cell wall

32
Q

How does glucose/amino acids/nucleosides cross BBB?

A

Active transport

33
Q

How does albumin/other plasma proteins cross BBB?

A

Adsorptive transcytosis

34
Q

How does a drug get out of the CSF?

A

Circulates around until it leaves through arachnoid villus

35
Q

Is there a significant barrier between the brain and CSF?

A

No

36
Q

Can drugs alter the permeability of BBB?

A

Yes

37
Q

What are 7 mechanisms of Neurotoxicity?

A

Interfering with aerobic metabolism (eg CO)
Interfering with protein synthesis (methyl Hg)
Interfering with Intermediate metabolism (MPTP)
Alter electrical transmission (tetrodotoxin)
Plant neurotoxins (vinka alkaloids)
Damage to myelin sheaths (hexachlorophene)
Selective Cytotoxicity (…)

38
Q

What are 3 ways for NT transmission that can be affected?

A

Increase/Decrease NT release
(Indirect effect) Synaptic modulation
Prevent transmitter reaction/reuptake

39
Q

What happened during the domoic acid epidemic of 1987?

A

Several cases of the same unusual symptoms (CNS problems but also GIT issues)
Many people died/suffered memory loss
*Excitation followed by neuronal necrosis

Turns out they had all eaten muscles fro PEI that were affected by algae to produce DOMOIC ACID

Domoic acid - heat stable, cooking didn’t denature it

Excites glutamate receptors - agonism followed by inactivation of neurons (prolongs opening of pre/post synaptic Na channels)
Na depolarization opens Ca channels, which is cytotoxic in cells

“Excitotoxicity”

40
Q

How does Saxitoxin kill you?

A

Numbs everything (diaphragm numbness, can’t breathe)

41
Q

How does Bioaccumulation kill larger animals?

A

Small amounts of toxin in small eg algae
Fish eat lots of algae - lots of toxin in fish
People eat lots of fish - LOTS of toxin in people

42
Q

How are some animals immune to tetrodotoxin?

A

Different Na channels that aren’t affected by TDT

43
Q

Is betrachotoxin safe to eat?

A

Yes, inactivated by stomach/cooking

44
Q

Is betrachotoxin produced by tree frogs?

A

No, the frogs eat the insec that makes it and concentrates it

45
Q

What is the main mechanism of bacterial neurotoxins?

A

Affect NT release

46
Q

What are the two most common bacterial neurotoxins?

A

Botulinum and Tetanus toxin

Both are 2-chain polypeptides

47
Q

When is botulinum toxin a risk?

A

In low acid home canning

48
Q

Describe the funciton of each polypeptide chain of Botulinum and Tetanus Toxin

A

Heavy Chain - one side locates cholinergic neurons, other side translocates into cell
Light Chain - does the damage:
Breaks down SNARE complex (normally incorporates vescicles)
Doesn’t destroy neuron but breaks that branch (permanent nerve damage)

49
Q

How can botulinum be used therapeutically?

A

Can treat hypercontractility by targeting specific nerves (botox)
Achalasia (contraction of esophageal sphincter

50
Q

True/False? Tetanus toxin funcitons in the same way as botulinum

A

True

51
Q

True/False? Tetanus toxin functions in the same palce as botulinum

A

False
BT - Brain
TT - Spinal Chord, specific to cholinergic receptors

52
Q

What are the symptoms of tetanus toxicity?

A

Spasm and Paralysis

Different from botulism in that it doesn’t effect that specific neuron, but the neuron inhibitory to that neuron

53
Q

How does the Latrotoxin of Black widow Spiders work?

A

Acts at neuromuscular junction, Creates a Ca Channel on nerve ending, allows NT flooding (LETHAL)

54
Q

How does alpha Bungarotoxin work?

A

Binds to muscular receptors
Irreversibly blocks Nicotinic Cholinergic receptors
Paralysis, diaphragmatic shock

55
Q

How does Sarin (an organophosphate) work?

A

Prevents inactivation of NT
Normally: Postsynaptic membrane has receptors that receive and break down ACh (and reuptakes metabolites)
Sarin is an “anticholinesterase”
AChE is inactivated, you die quickly

56
Q

What i the safest insecticide for mammals?

A

Malathion

57
Q

How are organophosphate insecticides absorbed?

A

Through the skin

58
Q

Is there an antidote for Organophosphate toxicity?

A

Yes! Pralidoxime (reactivates AChE, rips off organophosphates)

59
Q

Describe Lead toxicity

A

Brain/nerve damage
GI damage
Stunted Growth
Hearing Loss

60
Q

There is a direct relationship between placental concentration of _____ and emotional/behavioural problems

A

Lead

61
Q

How does lead lead to brain damage?

A

Interference with synapse function

Phar 303 (19 decks)

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