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NSCI 4501 > Past Exam Questions > Flashcards

Past Exam Questions Flashcards

1
Q

During excitotoxicity, the overactivation of glutamate NMDA receptors leads to

A

massive influx of Ca2+ and Na+ ions

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2
Q

During excitotoxicity, the overactivation of glutamate NMDA receptors leads to massive influx of Ca2+ and Na+ ions. What major downstream events cause neuronal cell death? (Select all that apply)

  • activation of Ca2+-sensitive proteases
  • ATP production shutdown
  • membrane budding
  • osmotic swelling
  • cellular shrinking
A
  • activation of Ca2+ sensitive proteases
  • ATP production shutdown
  • osmotic swelling
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3
Q

Bcl-2 family members are known to play a role in

A

both survival and apoptosis

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4
Q

Which of the following are key molecules related to neuronal apoptosis? (Select all that apply)

  • Bcl-2 family proteins
  • Apaf-1 (Apoptosis activating factor-1)
  • RIP1 (Receptor-interacting protein 1)
  • Active MLKL (mixed-lineage kinase domain like)
A
  • Bcl-2 family proteins
  • Apaf-1 (Apoptosis activating factor-1)
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5
Q

Among those listed below, which event leads to the execution of necroptosis?

  • RIP kinase inactivation
  • dimerization of LAMP2
  • multimerization of MLKL
A
  • multimerization of MLKL
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6
Q

what MAP is found in axons

A

Tau (MAPT)

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7
Q

fission and fusion require

A

energy

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8
Q

Which if the following complexes is a site of superoxide (O*2) production in the mitochondrial electron transport chain: (Select all that apply)

  • Complex I (NADH-ubiquinone reductase)
  • Complex II (Succinate-ubiquinone oxidoreductase)
  • Complex III (Ubiquinol cytochrome c oxidoreductase)
  • Complex IV (cytochrome c oxidase)
  • Complex V (F1F0-ATP synthase)
A
  • Complex 1
  • complex 3
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9
Q

The electron transport system resides in the _______ membrane of mitochondria and transfers electrons through a series of ______ reactions. This is done by each complex in the system transporting _____ out of the matrix.

A

inner, redox reactions, protons

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10
Q

sequence of the lactate shuttle hypothesis

A

Glutamate released by neurons → glutamate captured by astrocytes → astrocytes convert glutamate to glutamine → neurons take up lactate → neurons convert lactate to pyruvate

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11
Q

astrocytes possess a

A

high glycolysis capacity

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12
Q

T or F: astrocytes rely primarily on oxidative phosphorylation for ATP production

A

false, rely on glycolysis

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13
Q

T or F: neurons store glycogen

A

F, astrocytes store glycogen

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14
Q

_ express the pyruvate kinase M2

A

astrocytes

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15
Q

insulin activates what major pathways

A
  • mTOR
  • SOS/Grb2
  • Akt
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16
Q

the family of molecular chaperones involved in late-stage protein folding and targeting substrates for proteolysis

A

HSP90

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17
Q

In which state are folded proteins most likely to become thermodynamically “stuck” and most difficult for chaperones to remodel?

A

fibrils

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18
Q

Which UPR pathways involves splicing of the XBP1 mRNA?

A

IRE1 alpha dependent pathway

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19
Q

What proteins are known to play a central role in regulating mitophagy

A
  • parkin
  • pink1
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20
Q

Proteins targeted for chaperone-mediated autophagy contain a ______ motif allowing ______ to bind.

A

KFERQ, HSC70

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21
Q

Which form of autophagy relies upon the involvement of p62 and NBR1 as cargo receptors?

A

aggrephagy

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22
Q

Amyloids are insoluble fibrillary protein aggregates which constitute common pathologic feature of many neurodegenerative diseases. What molecular determinants characterize these deposits?

A
  • they share a cross-β pattern by X-ray diffraction studies
  • they are composed of one protein
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23
Q

Secondary nucleation refers to what process in amyloid fibril formation?

A

The formation of new amyloid fibrils from contact of amyloid monomers to pre-existing fibrils

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24
Q

What are some strategies cells use to combat protein aggregation? (Select all that apply)

  • Remodeling via chaperones
  • Disaggregation via chaperones
  • Removal of aggregates via internal transport
  • Degradation of proteins via autophagy
A
  • Remodeling via chaperones
  • Disaggregation via chaperones
  • Degradation of proteins via autophagy
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25
Q

Deleterious mutations in the NF1 gene cause an autosomal dominant condition called Neurofibromatosis. In a typical pedigree, all family members inheriting the NF1 mutation show symptoms of the condition, but the severity of these symptoms can present very differently from one affected individual to another. This is an example of:

A

Broad Expressivity

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26
Q

Examples of post translatoinal histone modifications that constitue an epigenetic mechanism

A
  • acetylation
  • methylation
  • phosphorylation
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27
Q

T or F: glycosylation is an epigenetic change to post translationally histone

A

false

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28
Q

T or F: Cre-LoxP system requires endonucleases

A

F

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29
Q

T or F: Cre-LoxP system can be used for insertaion or deletion of genes

A

T

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30
Q

Components needed for CRISPR

A
  • Cas9
  • Guide RNA
  • Target sequence
  • PAM site
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31
Q

To better understand the role of α-synuclein, the main component of inclusions in Parkinson’s disease, you want to create a novel conditional mouse line. With the agreement of your thesis supervisor, you decide to order a pCaMKIIα-Cre line and a line in which the SNCA gene (encoding for α-synuclein) is flanked by LoxP sites to perform your studies. What will happen to your F1 bigenic mice?

A

the expression of SNCA will be ablated in neurons expressing CaMKIIα

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32
Q

Complement protein cascades generally follow 1 of 2 pathways: the ___________ pathway in which a number of microorganisms spontaneously activate the complement system or the __________ pathway that is activated by antibodies bound to the pathogen surface.

A

alternative, classic

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33
Q

Vaccines induce a ______ antibody response meaning that if natural infection occurs a _______ antibody response is triggered to fight infection.

A

primary, secondary

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34
Q

Which cytokines drive T cell division and activation during antigen presentation?

A

IL-2 & IL-4

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35
Q

Identify the FALSE statement about memory T or B cells.

  • Have previously encountered and responded to a particular antigen
  • Survive in an inactive state in the host for a short period of time
  • At a second encounter with the antigen, memory T or B cells can reproduce to mount a faster and stronger immune response than the first time the immune system responded to the antigen
A

Survive in an inactive state in the host for a short period of time

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36
Q

Which cells initiate inflammation?

A

resident monocytes

37
Q

Identify the TRUE statements about M1 microglia.

  • produce various pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6, as well as superoxide, ROS and NO
  • promote extracellular matrix reconstruction and tissue repair
  • support neuron survival by producing neurotrophic factors
  • none of the above
A
  • produce various pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6, as well as superoxide, ROS and NO
38
Q

In Fragile X syndrome (FXS), what is the major consequence of the loss of function of the fragile X mental retardation protein (FMRP)?

A

Excessive signaling through metabotropic glutamate receptors

39
Q

Fragile X syndrome shows _ pattern of inheritance

A

non standard X-linked dominant

40
Q

FMRP associates with _ and controls _ by _

A

polyribosomes in dendrites, local protein synthesis by inhibiting translation.

41
Q

T or F: Anticipation is a clinical phenomenon describing progressively earlier onset of disease with increasing severity in successive generations.

A

T

42
Q

T or F: Trinucleotide repeats are stably transmitted from parent to offspring.

A

F

43
Q

T or F: Number of repeats in trinucleotide repeat diseases correlates inversely with severity of disease symptoms.

A

F

44
Q

T or F: In trinucleotide repeat expansion diseases, number of triplets present in a mutated gene is greater than the number found in a normal gene.

A

T

45
Q

Which of the following are common symptoms of spinocerebellar ataxia type 1 (SCA1)? (Select all that apply).

  • ataxia
  • dysphagia
  • tremor
  • mild cognitive impariment
  • weight loss
A
  • ataxia
  • dysphagia
  • mild cognitive impariment
46
Q

You hypothesize that motor deficits in SCA1 are caused by gain of mutant ATXN1 function. Which of the following experimental findings provides support to your hypothesis? (Select all that apply)
* Transgenic mice expressing full-length human ATXN1 with 82 CAGs (ATXN1[82Q]) develop motor deficits
* ATXN1-null mice are embryonic lethal.
* ATXN1-null mice do not develop motor deficits.
* Atxn1154Q/2Q mice develop cognitive deficits.

A
  • Transgenic mice expressing full-length human ATXN1 with 82 CAGs (ATXN1[82Q]) develop motor deficits
  • ATXN1-null mice do not develop motor deficits.
47
Q

In Huntington’s disease (HD), the development of mutant huntingtin (mHTT) inclusions in neurons are:

A

related to protective mechanisms

48
Q

HD is caused by…

A

abnormal CAG expansion in the exon1 in HTT gene

49
Q

mutant HTT leads to a decrease…

A

in the expression of BDNF

50
Q

what neurons are first lost in HD

A

indirect pathway spiny projection neurons (D2 receptor expressing).

51
Q

T or F: Huntingtin-null mice are phenotypically normal.

A

F

52
Q

T or F: R6/2 transgenic mice that express N-terminal fragment of mutant Htt demonstrate loss of weight that is typical of HD.

A

T

53
Q

Breeding mouse models of HD with BDNF overexpressing transgenic mice would test…

A

whether decrease in BDNF contributes to the HD phenotype in mice.

54
Q

In Multiple sclerosis (MS), which of the following are related to antigen presentation? (Select all that apply)

  • T-cell receptors
  • HLA-DRB1
  • HLA-A
  • TNFalpha,beta
  • Apolipoprotein E4
A
  • T-cell receptors
  • HLA-DRB1
  • HLA-A
55
Q

T or F: Sex hormones influence the development of MS.

A

T

56
Q

Identify the cells that are the major immune player in multiple sclerosis (MS).

A

T cells, B cells, microglia/macrophages

57
Q

IFN-β treatment in MS does what

A
  • antagonizes IFN-γ-mediated MHC-upregulation on APCs.
  • inhibits T cell activation and proliferation.
  • has no effect on progressive MS.
58
Q

best model to study relapsing-remitting multiple sclerosis (MS)?

A

SJL-TMEV model

59
Q

Which of the following mechanisms is potentially responsible for remyelination failure in multiple sclerosis (MS)?

  • inflammation
  • the lesion microenvironment
  • aging
  • depletion of oligodendrocyte precursor cells (OPCs)
A

all

60
Q

NAA is a neuronal marker that can be detected through the use of

A

MRS

61
Q

MRI modalities would be most insightful for studies of structural connectivity in the brain?

A

diffusion MRI

62
Q

Some studies reported a reduction in brain glutathione in amyotrophic lateral sclerosis (ALS) via brain imaging. This reduction in glutathione might indicate that:

A

antioxidant defenses in the body are diminished

63
Q

FDG PET to assess…

A

regional glucose uptake and phosphorylation

64
Q

_ to evalute regional atrophy

A

structural MRI

65
Q

_ for quanitfying high energy phosphates

A

31P MRS

65
Q

_ for quanitfying high energy phosphates

A

31P MRS

66
Q

What are the pitfalls of detecting amyloid fibril deposition by PET

A
  • variable [11C]-PIB binding in controls and subjects with MCI
  • amyloid-beta burden does not strongly correlate with cognitive impairment in AD.
67
Q

Under normal conditions, ________ is the main microtubule-associated protein found in dendrites, while ________ is found in axons.

A

MAP2, MAPT

68
Q

Which microtubule-binding domain (or R) is absent in 3R Tau isoforms?

A

the second

69
Q

Which diseases may present with 3R tau pathology?

A

Pick’s disease
Alzheimer’s disease

70
Q

Which of the following diseases belong to the superfamily of Asymmetrical Neurodegenerative Disease? (Select two)

  • Alzheimer’s disease
  • Parkinson’s disease
  • Huntington’s disease
  • Frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17)
  • Pick’s disease
A
  • Frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17)
  • Pick’s disease
71
Q

Some variants of frontotemporal dementia (FTD) present with an atrophy of language centers. What are these regions?

A
  • Broca’s area
  • Wernicke’s area
72
Q

The brain of a young professional boxer who committed suicide is most likely to contain which of the following pathologies? (Select Two)

  • Tau deposits in sulcal depths
  • Tau deposits in perivascular regions
  • Extensive amyloid plaques
  • Lewy bodies
  • Nuclear Tau rods
A
  • Tau deposits in sulcal depths
  • Tau deposits in perivascular regions
73
Q

Which symptoms can be present in individuals diagnosed with chronic traumatic encephalopathy (CTE)?

A
  • Cognitive deficits
  • Poor decision making and judgement
  • Depression and high risk of suicide
  • Motor deficits
74
Q

Which symptoms of ALS derive from lower motor neuron degeneration? (Select all that apply)

  • muscle weakness
  • fasciculations
  • muscle atrophy
  • spasticity
  • hyperreflexia
A
  • muscle weakness
  • fasciculations
  • muscle atrophy
75
Q

What are the main symptoms of bulbar-onset ALS?

A

Difficulty of swallowing and talking, jaw fasciculations, reduced gag reflex

76
Q

Amongst the proposed molecular mechanisms underlying ALS, which major pathogenic mechanism is thought to result from TDP43 dysfunction?

A

RNA processing

77
Q

In Spinal muscular atrophy (SMA), which CNS structure undergoes neurodegeneration?

A

Ventral horns of the spinal cord

78
Q

Which current treatment for SMA is a disease-modifying therapy?

A

SMNRx (Nusinersen®)

79
Q

Propagation of toxic protein aggregates is a hallmark of the progression of Alzheimer’s disease neuropathology. In general, tau pathology begins in ________ areas and propagates to ________ areas, while Aβ pathology begins in ________ areas and propagates to ________ areas.

A

hippocampal; neocortical; cortical; subcortical

80
Q

Which of the following are cognitive tests widely used in the clinic to diagnose Alzheimer’s disease-related deficits in patients? (Select all that apply)

A
  • MMSE
  • Mini cog
81
Q

Related to the amyloid precursor protein (APP) processing, which secretase is responsible for the non-amyloidogenic pathway?

A

alpha secretase

82
Q

__________ is preferentially active in early-stage endosomes, while _______ is mostly active in multivesicular bodies.

A

beta secreatse, gamma secreatse

83
Q

Which molecular component of the γ-secretase complex is responsible for the substrate selectivity of that complex?

A

NCT

84
Q

Which early pathogenic event in the amyloid cascade hypothesis has been proposed to underlie Aβ accumulation in sporadic Alzheimer’s disease?

A

decrease in Abeta clearance

85
Q

When mutated, which genes cause early-onset Alzheimer’s disease?

A
  • PSEN1
  • PSEN2
  • APP
86
Q

Which phenotype of Alzheimer’s disease is NOT reproduced in APP transgenic mouse models?

A

NFT

87
Q

Region X has recently been shown to be associated with Alzheimer’s disease. To validate these findings with imaging techniques, you could look for: (select all that apply)

  • Glucose hypermetabolism
  • Increased Pittsburg compound B labeling
  • Decreased Pittsburg compound B labeling
  • Glucose hypometabolism
  • Atrophy of region X
A
  • Increased Pittsburg compound B labeling
  • Glucose hypometabolism
  • Atrophy of region X

NSCI 4501 (5 decks)

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