Final Exam Study Flashcards
1
Q
Where does apoptosis occur?
A
Throughout all of the CNS
2
Q
How many caspase-dependent pathways are there and what are they?
A
2; extrinsic and intrinsic
3
Q
The interaction and activation of the members of Bcl-2 proteins are crucial for initiation of which pathway of apoptosis?
A
Intrinsic
4
Q
_____ prevents apoptosis during early neurulation
A
Bcl-2
5
Q
______ prevents the apoptosis of post-mitotic immature neurons of the developing brain, spinal cord, and dorsal root ganglia
A
Bcl-XL
6
Q
_____ is essential for promoting development during early enmbryogenesis
A
MCL-1
7
Q
Is MCL-1 pro- or anti-apoptotic?
A
Anti-apoptotic
8
Q
What are the initiator caspases?
A
Cascade 8, 9, and 10
9
Q
What are the effector caspases?
A
Caspase 1, 2,3,4,5,6,7,11,12, and 13
10
Q
What are the caspase activators and inhibitors?
A
Apaf-1, FADD, and C-FLIP
11
Q
What is the most effector caspase?
A
Caspase-3
12
Q
Effector caspases cleave many important intracellular substrates including:
A
- Morphological changes in apoptosis such as chromatin condensation
2- nucleosomal DNA fragmentation
3- breakdown of nuclear envelope
4- formation of apoptotic bodies
13
Q
What are the cytosolic proteins?
A
- Cytochrome C
- Smac/Diablo
- HtrA2
- IAP Binding proteins
14
Q
What is the master apoptotic protein?
A
Cytochrome C
15
Q
What proteins act on caspase 9?
A
Cytochrome C and Smac
16
Q
What kind of caspase is caspase 9?
A
An intiator caspase
17
Q
True or False: caspase 8 is involved in the intrinsic pathway
A
False, it is part of the extrinsic pathway
18
Q
What is the intrinsic pathway dependent on?
A
Permeabilization of the outer mitochondrial membrane
19
Q
What are a family of growth factors(nerve growth factors), involved in survival, development, and functions of neurons?
A
Neurotropins
20
Q
What is a low affinity receptor that binds NGF and stimulates neuronal cells to survive and differentiate?
A
Neurotropin receptor (p75NTR)
21
Q
What is a multifunctional cytokine that regulates cell survival, proliferation, differentiation, and apoptosis?
A
Tumor Necrosis Factor (TNF)
22
Q
What is a high receptor for the neurotropin , NGF involved in multiple functions including neuronal differentiation, synaptic strength, and plasticity?
A
TrkA
23
Q
Caspase _________ mechanism involves the release of apoptosis-inducing factor (AIF)
A
Independent
24
Q
Once in the cytosol, what does AIF not require since it can easily act on the nucleus ?
A
Any intermediate
25
Calcium mediates a ____-apoptotic protein-independent pathway, leading to the mitochondrial involvement in neuronal loss
Pro
26
What does Ca2+ stress activate which generates 2 proapoptotic signals in the_____pathway CT
Intronsic
27
True or False: developing sympathetic neurons require nerve growth factor (NGF) for survival during late embryonic and early post-natal development
True
28
NGF ______ activates mitochondrial pathway of apoptosis
withdrawal
29
Bax and cytochrome c are part of which pathway?
Intrinsic
30
If caspase 9 is not changed, what does it mean?
It is the intrinsic pathway that is involved
31
If caspase 8 does not change, what is it mediated by?
The intrinsic pathway
32
do PCBs (polychlorinated biphenyls) increase or decrease apoptosis?
increase
33
Maternal smoking has what kind of effect on the fetus' head and brain size?
it causes microcephaly and microencephaly
34
What are the adverse outcomes that are at risk with smoking while pregnant?
- reduced fetal growth
- spontaneous abortion
- preterm birth
- SIDS
- Increased chance of the baby dying at or shortly after birth
35
True or False: There is a safe level of smoking
FALSE
36
What are the two important effects of maternal smoking?
1. born small for gestational age (SGA) (<5.5 pounds)
2. smaller head circumference (microencephaly)
37
Children of women who smoke while pregnant experience what three things?
1. have more behavioral and emotional disorders
2. lower cognitive abilities
3. increased risk of smoking themselves
38
What are the compounds of interest in cigarette smoke?
- nicotine
- carbon monoxide
- tar
- benzene
- heavy metals, such as lead and cadmium
- arsenic
39
True or False: second-hand smoke is a risk factors for SIDS?
TRUE
40
Up to 60% of SIDS cases show histopathological evidence of hypoplasia of the _____ ______
arcuate nucleus
41
What is the arcuate nucleus?
an integrative site for vital autonomic functions
42
________ and _______ ________ cause vasoconstriction in the placenta and cross the placenta and enter fetal tissue
nicotine and carbon monoxide
43
nicotine from cigarette smoke is easily absorbed due to its high ______ ________
lipid solubility
44
Nicotine and its main metabolite, cotinine, rapidly cross the __________ tissue into the embryonic and fetal bloodstream
placental
45
What has been the first major focus of most studies of smoking during pregnancy because of its addictive properties and its known neurotoxicity?
nicotine
46
What is the major metabolite in nicotine?
cotinine
47
What is the first site of metabolism in nicotine?
the Lung
48
What is the major/main site of metabolism of nicotine?
liver
49
What is the half-life of nicotine vs the half-life of cotinine?
nicotine: about 2 hours
cotinine: about 18-20 hours
50
Is the fetus exposed to higher or lower nicotine concentrations compared to the smoking mother?
Higher
51
Where are nicotine and metabolites excreted?
primarily in urine and breast milk
52
What is the receptor that nicotine binds to as a ligand?
nAChRs
53
nicotine's receptors are expressed by both neuronal and non-neuronal cells in the brain tissues with _______ affinity
high
54
What kind of cholenergic system is associated with numerous cell functions, including proliferation, differentiation, migration, and apoptosis?
non-neuronal
55
What does it mean to be heteromeric?
subunits are different and less permeable to calcium
56
What happens when Heteromeric subunits are activated by ACh?
it results in membrane depolarization
57
What does it mean to be Homomeric?
the subunits are the same and are more permeable to calcium
58
What are Homomeric subunits activated by? what does this lead to?
activated by both choline and ACh; this leads to calcium influx
59
The _____ ______ is the part of the hippocampal formation and plays a critical role in learning and memory
dentate gyrus
60
Chronic tobacco smoke _________ cell proliferation and cell survival
decreases
61
What are involved in the regulation of the vesicle pool at the presynaptic terminals, elongation of axons, and synaptic vesicle docking?
synapsins
62
what calcium binding protein is associated with presynaptic vesicles of neurons?
synaptophysin
63
What is a major scaffolding protein in the excitatory postsynaptic density that is involved in the regulation of synaptic strength?
PSD-95
64
What two groups are pesticides divided into?
inorganic and organic compounds
65
pesticides are classified based on their:
1. chemical structure
2. environmental stability and toxicity
3. the pathways by which they penetrate and affect target organisms
66
What represents the most important source of exposure?
food supply
67
What are some common types of insecticides?
- organophosphates
- neonicotinoids
- carbamates
(and more)
68
Rate the toxicity of: organophosphates
most ops are highly toxic
69
Rate the toxicity of:
organochlorides
high toxicity
70
Rate the toxicity of:
Pyrethrins and Pyrethroids
low to moderate toxicity
71
Rate the toxicity of:
N-methyl carbamates
moderate to highly toxic
72
Rate the toxicity of:
Neonicotinoids
lower toxicity than ops and carbamates
73
OP (organophosphate pesticides) are known to by highly toxic, but their biological half-life is ________ compared to pesticides such as organochlorine presicides
shorter
74
What effects do OPs have on children's attention, mental flexibility, as well as conceptual flexibility?
deleterious effects
75
What kind of inhibitors are organophosphates?
AChE inhibitors
76
Organophosphates (AChE inhibitors) increase the amount of ACh in the synaptic cleft which then leads to?
overstimulation of Ach Receptors
77
Organophosphorus causes the inhibition of ____ in the brain's cholinergic synapses and neuromuscular junctions
AchE
78
Inhibition of AchE lead stop excessive activation of which receptors in the PNS and CNS?
muscarinic and nicotinic receptors
79
ACh is broken down by AchE into what two things?
choline and acetate
80
What happens to choline once AchE has broken down Ach?
it goes back to the presynaptic neuron to make more ACh
81
What two things together synthesize ACh?
choline and acetyl CoA
82
What are Chlorpyrifos shown to be involved in?
developmental neurotoxicity
83
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
True
84
What is the main target of organophosphate pesticides?
AChE at the synapse
85
What is Chlorpyrifos?
a very potent neurotoxic organophosphorus (OP) insecticide
86
What three things does the mechanism of action of Chlorpyrifos include of AChE in brain cholinergic synapses?
excitotoxicity, oxidative stress, and irreversible inhibition
87
What is one of the most commonly used organophosphates and is ranked fourth in targeting the nervous system?
Malathion
88
What happens to the level of BDNF in the brain when treated with Malathion?
it decreases
89
Air pollutants contribute to brain effects through which two main routes?
1. Nasal Pathway
2. The respiratory intake pathway
90
What happens when air pollutants enter through the nasal pathway?
air pollutants enter through inhalation and cross the olfactory mucosa to reach the brain directly
91
What happens when air pollutants enter through the respiratory intake pathway?
air pollutants enter the brain by passing from the lungs into the bloodstream and through the blood-brain barrier
92
Exposure to air pollution has what effect on the child's brain?
- causes child brain structural alterations of the cerebral cortex
- thinner cortex in several brain regions
93
Air pollutants may affect other organ systems that (directly/indirectly), adversely affect CNS development
indirectly
94
