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Developmental Neurotoxicology 2nd Half > Final Exam Study > Flashcards

Final Exam Study Flashcards

1
Q

Where does apoptosis occur?

A

Throughout all of the CNS

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2
Q

How many caspase-dependent pathways are there and what are they?

A

2; extrinsic and intrinsic

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3
Q

The interaction and activation of the members of Bcl-2 proteins are crucial for initiation of which pathway of apoptosis?

A

Intrinsic

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4
Q

_____ prevents apoptosis during early neurulation

A

Bcl-2

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5
Q

______ prevents the apoptosis of post-mitotic immature neurons of the developing brain, spinal cord, and dorsal root ganglia

A

Bcl-XL

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6
Q

_____ is essential for promoting development during early enmbryogenesis

A

MCL-1

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7
Q

Is MCL-1 pro- or anti-apoptotic?

A

Anti-apoptotic

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8
Q

What are the initiator caspases?

A

Cascade 8, 9, and 10

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9
Q

What are the effector caspases?

A

Caspase 1, 2,3,4,5,6,7,11,12, and 13

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10
Q

What are the caspase activators and inhibitors?

A

Apaf-1, FADD, and C-FLIP

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11
Q

What is the most effector caspase?

A

Caspase-3

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12
Q

Effector caspases cleave many important intracellular substrates including:

A
  1. Morphological changes in apoptosis such as chromatin condensation
    2- nucleosomal DNA fragmentation
    3- breakdown of nuclear envelope
    4- formation of apoptotic bodies
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13
Q

What are the cytosolic proteins?

A
  1. Cytochrome C
  2. Smac/Diablo
  3. HtrA2
  4. IAP Binding proteins
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14
Q

What is the master apoptotic protein?

A

Cytochrome C

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15
Q

What proteins act on caspase 9?

A

Cytochrome C and Smac

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16
Q

What kind of caspase is caspase 9?

A

An intiator caspase

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17
Q

True or False: caspase 8 is involved in the intrinsic pathway

A

False, it is part of the extrinsic pathway

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18
Q

What is the intrinsic pathway dependent on?

A

Permeabilization of the outer mitochondrial membrane

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19
Q

What are a family of growth factors(nerve growth factors), involved in survival, development, and functions of neurons?

A

Neurotropins

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20
Q

What is a low affinity receptor that binds NGF and stimulates neuronal cells to survive and differentiate?

A

Neurotropin receptor (p75NTR)

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21
Q

What is a multifunctional cytokine that regulates cell survival, proliferation, differentiation, and apoptosis?

A

Tumor Necrosis Factor (TNF)

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22
Q

What is a high receptor for the neurotropin , NGF involved in multiple functions including neuronal differentiation, synaptic strength, and plasticity?

A

TrkA

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23
Q

Caspase _________ mechanism involves the release of apoptosis-inducing factor (AIF)

A

Independent

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24
Q

Once in the cytosol, what does AIF not require since it can easily act on the nucleus ?

A

Any intermediate

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25
Q

Calcium mediates a ____-apoptotic protein-independent pathway, leading to the mitochondrial involvement in neuronal loss

A

Pro

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26
Q

What does Ca2+ stress activate which generates 2 proapoptotic signals in the_____pathway CT

A

Intronsic

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27
Q

True or False: developing sympathetic neurons require nerve growth factor (NGF) for survival during late embryonic and early post-natal development

A

True

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28
Q

NGF ______ activates mitochondrial pathway of apoptosis

A

withdrawal

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29
Q

Bax and cytochrome c are part of which pathway?

A

Intrinsic

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30
Q

If caspase 9 is not changed, what does it mean?

A

It is the intrinsic pathway that is involved

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31
Q

If caspase 8 does not change, what is it mediated by?

A

The intrinsic pathway

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32
Q

do PCBs (polychlorinated biphenyls) increase or decrease apoptosis?

A

increase

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33
Q

Maternal smoking has what kind of effect on the fetus’ head and brain size?

A

it causes microcephaly and microencephaly

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34
Q

What are the adverse outcomes that are at risk with smoking while pregnant?

A
  • reduced fetal growth
  • spontaneous abortion
  • preterm birth
  • SIDS
  • Increased chance of the baby dying at or shortly after birth
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35
Q

True or False: There is a safe level of smoking

A

FALSE

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36
Q

What are the two important effects of maternal smoking?

A
  1. born small for gestational age (SGA) (<5.5 pounds)
  2. smaller head circumference (microencephaly)
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37
Q

Children of women who smoke while pregnant experience what three things?

A
  1. have more behavioral and emotional disorders
  2. lower cognitive abilities
  3. increased risk of smoking themselves
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38
Q

What are the compounds of interest in cigarette smoke?

A
  • nicotine
  • carbon monoxide
  • tar
  • benzene
  • heavy metals, such as lead and cadmium
  • arsenic
39
Q

True or False: second-hand smoke is a risk factors for SIDS?

A

TRUE

40
Q

Up to 60% of SIDS cases show histopathological evidence of hypoplasia of the _____ ______

A

arcuate nucleus

41
Q

What is the arcuate nucleus?

A

an integrative site for vital autonomic functions

42
Q

________ and _______ ________ cause vasoconstriction in the placenta and cross the placenta and enter fetal tissue

A

nicotine and carbon monoxide

43
Q

nicotine from cigarette smoke is easily absorbed due to its high ______ ________

A

lipid solubility

44
Q

Nicotine and its main metabolite, cotinine, rapidly cross the __________ tissue into the embryonic and fetal bloodstream

A

placental

45
Q

What has been the first major focus of most studies of smoking during pregnancy because of its addictive properties and its known neurotoxicity?

A

nicotine

46
Q

What is the major metabolite in nicotine?

A

cotinine

47
Q

What is the first site of metabolism in nicotine?

A

the Lung

48
Q

What is the major/main site of metabolism of nicotine?

A

liver

49
Q

What is the half-life of nicotine vs the half-life of cotinine?

A

nicotine: about 2 hours
cotinine: about 18-20 hours

50
Q

Is the fetus exposed to higher or lower nicotine concentrations compared to the smoking mother?

A

Higher

51
Q

Where are nicotine and metabolites excreted?

A

primarily in urine and breast milk

52
Q

What is the receptor that nicotine binds to as a ligand?

A

nAChRs

53
Q

nicotine’s receptors are expressed by both neuronal and non-neuronal cells in the brain tissues with _______ affinity

A

high

54
Q

What kind of cholenergic system is associated with numerous cell functions, including proliferation, differentiation, migration, and apoptosis?

A

non-neuronal

55
Q

What does it mean to be heteromeric?

A

subunits are different and less permeable to calcium

56
Q

What happens when Heteromeric subunits are activated by ACh?

A

it results in membrane depolarization

57
Q

What does it mean to be Homomeric?

A

the subunits are the same and are more permeable to calcium

58
Q

What are Homomeric subunits activated by? what does this lead to?

A

activated by both choline and ACh; this leads to calcium influx

59
Q

The _____ ______ is the part of the hippocampal formation and plays a critical role in learning and memory

A

dentate gyrus

60
Q

Chronic tobacco smoke _________ cell proliferation and cell survival

A

decreases

61
Q

What are involved in the regulation of the vesicle pool at the presynaptic terminals, elongation of axons, and synaptic vesicle docking?

A

synapsins

62
Q

what calcium binding protein is associated with presynaptic vesicles of neurons?

A

synaptophysin

63
Q

What is a major scaffolding protein in the excitatory postsynaptic density that is involved in the regulation of synaptic strength?

A

PSD-95

64
Q

What two groups are pesticides divided into?

A

inorganic and organic compounds

65
Q

pesticides are classified based on their:

A
  1. chemical structure
  2. environmental stability and toxicity
  3. the pathways by which they penetrate and affect target organisms
66
Q

What represents the most important source of exposure?

A

food supply

67
Q

What are some common types of insecticides?

A
  • organophosphates
  • neonicotinoids
  • carbamates
    (and more)
68
Q

Rate the toxicity of: organophosphates

A

most ops are highly toxic

69
Q

Rate the toxicity of:
organochlorides

A

high toxicity

70
Q

Rate the toxicity of:
Pyrethrins and Pyrethroids

A

low to moderate toxicity

71
Q

Rate the toxicity of:
N-methyl carbamates

A

moderate to highly toxic

72
Q

Rate the toxicity of:
Neonicotinoids

A

lower toxicity than ops and carbamates

73
Q

OP (organophosphate pesticides) are known to by highly toxic, but their biological half-life is ________ compared to pesticides such as organochlorine presicides

A

shorter

74
Q

What effects do OPs have on children’s attention, mental flexibility, as well as conceptual flexibility?

A

deleterious effects

75
Q

What kind of inhibitors are organophosphates?

A

AChE inhibitors

76
Q

Organophosphates (AChE inhibitors) increase the amount of ACh in the synaptic cleft which then leads to?

A

overstimulation of Ach Receptors

77
Q

Organophosphorus causes the inhibition of ____ in the brain’s cholinergic synapses and neuromuscular junctions

A

AchE

78
Q

Inhibition of AchE lead stop excessive activation of which receptors in the PNS and CNS?

A

muscarinic and nicotinic receptors

79
Q

ACh is broken down by AchE into what two things?

A

choline and acetate

80
Q

What happens to choline once AchE has broken down Ach?

A

it goes back to the presynaptic neuron to make more ACh

81
Q

What two things together synthesize ACh?

A

choline and acetyl CoA

82
Q

What are Chlorpyrifos shown to be involved in?

A

developmental neurotoxicity

83
Q

True or False: Prenatal or neonatal exposure of Chlorpyrifos has been reported to cause several behavioral abnormalities including lack of locomotor skills and cognitive function in mice and rats

A

True

84
Q

What is the main target of organophosphate pesticides?

A

AChE at the synapse

85
Q

What is Chlorpyrifos?

A

a very potent neurotoxic organophosphorus (OP) insecticide

86
Q

What three things does the mechanism of action of Chlorpyrifos include of AChE in brain cholinergic synapses?

A

excitotoxicity, oxidative stress, and irreversible inhibition

87
Q

What is one of the most commonly used organophosphates and is ranked fourth in targeting the nervous system?

A

Malathion

88
Q

What happens to the level of BDNF in the brain when treated with Malathion?

A

it decreases

89
Q

Air pollutants contribute to brain effects through which two main routes?

A
  1. Nasal Pathway
  2. The respiratory intake pathway
90
Q

What happens when air pollutants enter through the nasal pathway?

A

air pollutants enter through inhalation and cross the olfactory mucosa to reach the brain directly

91
Q

What happens when air pollutants enter through the respiratory intake pathway?

A

air pollutants enter the brain by passing from the lungs into the bloodstream and through the blood-brain barrier

92
Q

Exposure to air pollution has what effect on the child’s brain?

A
  • causes child brain structural alterations of the cerebral cortex
  • thinner cortex in several brain regions
93
Q

Air pollutants may affect other organ systems that (directly/indirectly), adversely affect CNS development

A

indirectly

94
Q
A

Developmental Neurotoxicology 2nd Half (11 decks)

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