Elsevier · Web viewNT dimer binds to Trk, Trk dimerizes, ligand-receptor complex transphosphorylates tyrosine residues, adaptor proteins bind to phosphorylation sites, adaptor proteins

Sanes Chapter 7 questions

[1] Does the weight of the human brain change after neurogenesis is complete?

a. Yes, it doubles in weightb. Yes, it adds over 3 times its weight*c. Yes, it adds over 5 times its weightd. Yes, it adds weight then loses weight by adulthood

[2] During development of the nervous system, programmed cell death is best defined as

a. Post-mitotic nerve cells that fail to reach their post-synaptic targets dieb. Post-mitotic nerve cells actively die through protein synthesis and gene

transcription*c. Depending upon the region of the brain 20% to 80% of differentiated post-

mitotic neurons degenerate during maturationd. None of these is a good definition

[3] To escape programmed cell death neurons receive survival signals from several sources; which one of these is NOT a source of these trophic factors?

a. Synaptic inputs from other neuronsb. Glial cells in the cellular matrixc. Blood-borne factors from distant sourcesd. Microtubules within the neuron itself*

[4] The general process by which programmed cell death usually occurs is called

a. Pyknosisb. Phagocytosisc. Apoptosis*d. Enzyme cleavage of DNA

[5] The purpose of TUNEL labeling is

a. To label DNA in dying neurons before fragmentationb. To detect the nuclei of dying neurons before the cells are phagocytosed*c. To detect phagocytosis of the cells of dying neurons

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d. To detect pyknosis in dying neurons

[6] A second form of programmed cell death, though to possibly be a late stage, is

a. An autophagic processb. An autolysosomic processc. An autophagosomic processd. All of these are correct*

[7] In necrosis as opposed to apoptosis neurons ________ as they degenerate.

a. Swell*b. Shrinkc. Remain approximately the same sized. None of these are correct

[8] The earliest stage of PCD eliminates some progenitor neural cells from the proliferative zone.

a. True*b. False

[9] In addition to the PCD of neurons, about ______ percent of oligodendrocytes in the rat optic nerve undergo PCD

a. 50*b. 20c. 37d. 67

[10] Difficulty in obtaining an accurate count of the number of neurons during development is exacerbated by

a. PCD and neurogenesis overlapping in timeb. Changes in the size of neurons during developmentc. Changes in the packing density of cells in neural tissued. All of these are correct*

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[11] Experiments that manipulate the afferent target of developing neurons such as removing muscle or transplanting an extra limb bud have shown that

a. The number of neurons that die off due to PCD is relatively constantb. The number of neurons that survive PCD varies according to the size of the

afferent target*c. The number of neurons that survive PCD is relatively constantd. There is little relationship between the size of the afferent target and the

number of neurons that survive PCD

[12] A disparity in the rate of PCD in pre- and post-synaptic nuclei in the embryonic chick auditory system strongly suggests that

a. Change in target size is the sole determinant of neuron survivalb. Change in target size is unrelated to neuron survivalc. Change in target size is one factor influencing neuron survival*d. None of these are correct

[13] Transient interactions of growing axons with nearby tissue, before the axons reach their targets, have virtually no effect on neuron survival.

a. Trueb. False*

[14] The Levi-Montalcini and Hamburger experiments in the early 1950’s, in which mouse tumor cells were transplanted into chick hind limb, demonstrated for the first time that

a. There was a diffusible chemical that influenced sensory neuron survival*b. Sensory neuron survival critically depended on afferent targetsc. Any target tissue could substitute for the hind limb muscle target for

regulating sensory neuron survivald. The only sensory neurons whose survival was affected by target tissue were

those making direct physical connections to the target

[15] The accidental discovery that snake venom had a growth-promoting effect on sympathetic ganglia suggested that

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a. NGF was not a protein because venom breaks down proteinsb. NGF was a nucleic acid because venom breaks down proteinsc. NGF could be found in mammalian salivary glands*d. NGF was found in many vertebrates but not mammals

[16] Placing cells from a sarcoma tumor line into a chick embryo on the chorioallantoic membrane, causes

a. All sympathetic and DRG to increase in size*b. Only ipsilateral sympathetic and DRG to increase in sizec. No changes in sympathetic and DRG growthd. None of these are correct

[17] Injecting an antibody directed against NGF in neonatal rodents demonstrated that

a. NGF is necessary for sympathetic neuron survivalb. NGF is not necessary for DRG cell survivalc. DRG cells can only be destroyed by prenatal exposure to NGF antibodyd. All of these are correct*

[18] NGF antibody treatment at an early embryonic stage of development will adversely affect the survival of all DRG cells and all sensory neurons.

a. Trueb. False*

[19] Some neurons may be NGF dependent and independent, at different stages of development.

a. True*b. False

[20] When brain derived growth factor (BDNF), was first purified and its amino acid sequence determined, its structure displayed a striking similarity to

a. NGF* b. NT-3c. NT-4/5

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d. NT-6

[21] The region of each neurotrophin that is responsible for its binding to a specific receptor are

a. The unique amino acid sequences*b. One or more of the six hydrophobic regionsc. The hodimers formed from the pro-peptidesd. All of these are true

[22] Different members of the neurotrophin family play a role in the survival of

a. Species-specific classes of neuronsb. General central neuron populationsc. Specific peripheral neuron populations*d. Neurons in most vertebrates except fish

[23] Neurotrophin ligands bind selectively to the tyrosine kinase family of receptors; NT-3 in particular binds

a. Selectively to the same receptor, TrkA, as NGFb. Selectively to the same receptor, TrkB, as BDNFc. Selectively to receptors that also bind NGF, BDNF and NT-4/5*d. Selectively to the same receptor, p75NTR, as proNGF

[24] Eliminating one of the Trk tyrosine kinase receptors and thus preventing one of the neurotrophins from binding to it, typically results in

a. Extensive cell death of a particular class of neurons such as the trigeminalb. Moderate to extensive cell death of several neuron classes*c. Few changes in PCD because of the redundant function of other receptorsd. General, unspecific changes in PCD

[25] The loss of NT-3 expression in single-gene knockout mice is likely to affect DRG neurons when they first extend their axons, well before reaching their target.

a. True*b. False

[26] Each TrK receptor gene is differentially spliced; trkC genes may encode for up to eight different TrkC receptor proteins.

a. True*

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b. False

[27] If a Trk receptor is activated in the absence of a neurotrophin, the process is called

a. Autophosphorylationb. Transactivation*c. Coactivationd. Non-neurotrophin activatio

[28] Each TrK receptor has a high specific affinity fora. A single neurotrophinb. One or two neurotrophins*c. All neurotrophinsd. None of these are correct

[29] Which tropomyosin related kinase proteins are high-affinity binding sites for neurotrophins?

a. TrkB which binds BDNF or NT-4b. TrkC which binds NT-3c. Both TrkB and TrkC are high-affinity binding sites*d. Neither TrkB and TrkC are high-affinity binding sites

[30] Any Trk receptor may be activated in the absence of any neurotrophin.a. True*b. False

[31] What is transactivation?a. TrkB receptor being activated by NGFb. TrkC receptor being activated by NGFc. A Trk receptor being activated from within the neuron*d. All of these are correct

[32] The observed pattern of NT-3 expression is that it is typically found surrounding

a. The end of the limb that is not yet innervatedb. Around DRG but not sensory motor projectionc. Around sensory motor projection, DRG but not the end of the limb*

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d. None of these are correct

[33] What is the best evidence that Trk receptors mediate survival signals to neurons?

a. Pc12 cells that lack TrkA protein do not respond to NGFb. Transgenic mice lacking Trk receptors display extensive neuron death in

specific neuron populationsc. TrkC receptor deletion leads to loss of half of cochlear ganglion neurons

even though nodose and trigeminal neurons are sparedd. All of these are supporting evidence for Trk receptor mediated survival

signals*

[34] If the axons of cholinergic cells in the basal forebrain are cut, exogenous NGF is able to keep them alive.

a. True*b. False

[35] If the axons of cholinergic cells in the basal forebrain are cut, exogenous NT-3 or NT-4 is able to keep them alive.

a. Trueb. False*

[36] In an experiment to determine how the neurotrophin NGF signal reaches the soma of the developing neuron, sympathetic neuron cell bodies were cultured in isolation from their neuritic processes. If the antibody against NGF is added to the cultured cell bodies and NGF is added to the growing neurites, 95% of the neurons survive; If the antibody against NGF is added to the cultured cell bodies and NGF covalently bound to beads is added to the growing neurites, 81% of the neurons survive. This demonstrates that

a. All of the NGF signal is acquired at the axon tipb. Most of the NGF signal is acquired at the axon tip*c. None of the NGF signal is acquired at the axon tipd. All of the NGF signal is acquired directly by the cell body

[37] The neurotrophin signal that enters the axon tip during neurite growth gets transported

a. Anterogradely to the cell nucleus along microtubules

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b. Retrogradely to the cell nucleus along microtubules*c. By diffusion through the extracellular mediumd. All of these are correct

[38] Neurotrophins released as uncleaved pro-peptides, which bind with high-affinity to the P75NTR, are also known as

a. Proneurotrophins*b. NGFc. NT-3 or NT-4d. BDNF

[39] The tumor necrosis factor receptor P75 differs from Trk receptors in that ita. Does not have an intracellular signaling pathway*b. Cannot activate intracellular signaling pathwaysc. Is not homologous with other members of the TNFR familyd. Has no ‘death domain’ analogous to the reaper gene in Drosophila

[40] Among the processes by which P75NTR influences neuron death or survival isa. Release of transcription activator NF-kB which enters the nucleusb. Release of neurotrophin receptor interacting factor which activates c-Jun N-

terminal kinase (JNK)c. c-Jun enters the nucleus to promote the transcription of pro-apoptotic

genesd. all of these are among those processes*

[41] The beta amyloid peptide binds to the P75NTR which may contribute to the degeneration of cholinergic brainstem neurons in Alzheimer’s

a. True*b. False

[42] The convention for naming a cytokine is a. derived from it’s most important biological functionb. derived from it’s first-discovered biological function*c. derived from the cells on which its receptor is locatedd. an arbitrary choice by the person who discovered it

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[43] Cytokines have been shown to act as pro-apoptotic signals but not to support neuron survival.

a. Trueb. False*

[44] Elimination of one growth factor alone will typically have a major effect on the survival of central neurons, unlike peripheral ganglion cells.

a. Trueb. False*

[45] Glial cell line-derived neurotrophic factor (GDNF)a. Prevents naturally-occurring motor neuron death b. Ligand-receptor complexes become associated with a transmembrane

tyrosine kinase (RET)c. Over-expression in mouse musculature led to increased survival of most

motor neuron populationsd. All of these are true*

[46] When neonatal male rats are castrated and reared with the androgen agonist, flutamide

a. There is an increased number of SNB motor neuronsb. There is a decreased number of SNB motor neurons*c. There is no change in the number of SNB motor neuronsd. Changes in the number of SNB motor neurons is independent of both

target muscle size and the type of treatment

[47] The differentiation of the sexually dimorphic nucleus of the preoptic area evidently arises because estradiol protects against apoptosis in these neurons.

a. True*b. False

[48] The earlier view was that endocrine signaling leading to sexual dimorphisms in songbird telencephalic nuclei arises because of

a. Selective loss of cells in malesb. Hormonal influences on cell survival in femalesc. Hormonal influences on cell survival in males*d. None of these are correct

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[49] The current view is that endocrine signaling leading to sexual dimorphisms in songbird telencephalic nuclei arises because of circulating steroid hormones secreted by testicular tissue

a. Trueb. False*

[50] A factor suggesting that steroid hormones widely influence naturally-occurring cell death in areas beyond the sexually dimorphic pre-optic area is that

a. Cell death in male rat primary visual cortex ends almost two weeks before that of females

b. Cell death in female sympathetic ganglia that innervate the face area is greater than in males

c. Both of these are true*d. Neither of these are true

[51] Circulating growth hormone (GH) released from the pituitary, acts directly on organs such as the liver to stimulate Insulin-like growth factor 1 (IGF-1); IGF-1 may also be synthesized in local regions of brain. If the expression of IGF-1 is genetically increased in mice, what happens to the cerebral cortex?

a. Natural PCD was inhibited and the surviving cells persisted to adulthood*b. Natural PCD was increased resulting in selective neuronal loss in certain

brain regionsc. The increased IGF-1 binds to TRs, creating a TH deficiencyd. Increased IGF-1 had no effect on PCD but dramatically increased the

number of TUNEL-positive cells in the ganglion cell layer

[52] Endocrine signals are responsible for remodeling the insect nervous system during metamorphosis

a. A large decrease in 20-hydroxecdysone triggers pupa formation in mothsb. A small increase in 20-hydroxecdysone triggers the death of specific

abdominal motor neurons in the moth*c. A large decrease in 20-hydroxecdysone triggers the molt in which the larva

sheds its cuticle and growsd. In fruit flies, when levels of 20-hydroxecdysone rise, neurons in the ventral

cord die

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[53] In vitro, sympathetic neurons die within two days if NGF is removed from the culture medium; these neurons can be rescued if

a. A translation blocker is added to the mediumb. A transcription blocker is added to the mediumc. Either of these is added to the medium*d. Neither of these is added to the medium

[54] If chick embryos are treated with either cycloheximide or actinomycin-D at the stage when the PCD of DRG and motor neurons is at a peak, what happens?

a. The number of pyknotic neurons decreasesb. Fewer DRG cells diec. Fewer motor neurons died. All of these are correct*

[55] Protein synthesis must occur in order for cells to die.a. True*b. False

[56] Gene transcription must occur in order for cells to die.a. True*b. False

[57] Which set is the correct sequence of neurotrophin signal transduction:a. NT dimer binds to Trk , Trk dimerizes, adaptor proteins bind to

phosphorylation sites, ligand-receptor complex transphosphorylates tyrosine residues, adaptor proteins are phosphorylated

b. NT dimer binds to Trk, adaptor proteins bind to phosphorylation sites, Trk dimerizes, ligand-receptor complex transphosphorylates tyrosine residues, adaptor proteins are phosphorylated

c. NT dimer binds to Trk, ligand-receptor complex transphosphorylates tyrosine residues, adaptor proteins bind to phosphorylation sites, Trk dimerizes, adaptor proteins are phosphorylated

d. NT dimer binds to Trk, Trk dimerizes, ligand-receptor complex transphosphorylates tyrosine residues, adaptor proteins bind to phosphorylation sites, adaptor proteins are phosphorylated*

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[58] Following the first phosphorylation of an adaptor protein (Shc), two intracellular pathways lead to the phosphorylation of cytoplasmic components that participate in cell survival; these are

a. P13K-Akt and MAPK pathways*b. JNK and Cdk pathwaysc. P13K-Akt and JNK pathwaysd. MAPK and Cdk pathways

[59] How do the two major NGF kinase pathways prevent cell death?a. Inactivating pro-apoptotic proteins in cytoplasm and increasing

transcription of anti-apoptotic proteins*b. Activating pro-apoptotic proteins in cytoplasm and increasing transcription

of anti-apoptotic proteinsc. Inactivating pro-apoptotic proteins in cytoplasm and decreasing

transcription of anti-apoptotic proteinsd. Activating pro-apoptotic proteins in cytoplasm and decreasing transcription

of anti-apoptotic proteins

[60] When neurotrophin-dependent neurons are deprived of NGF, what happens?a. The JNK pathway becomes activated, leading to cell death*b. The MAPK pathway becomes activated, leading to cell deathc. The JNK pathway becomes activated, leading to cell survivald. The MAPK pathway becomes activated, leading to cell survival

[61] Which is an example of a pro-apoptotic protein?a. CREBb. Rasc. Bcl-2d. Bim*

[62] Regarding the Cdk intracellular signaling pathway, the consequence, in vitro, of blockading cyclin-dependent kinases with Cdk inhibitors is to promote motor, sensory, sympathetic, retinal and cerebellar neuron death.

a. Trueb. False*

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[63] Apoptosis in C. elegans requires the expression of genes, ced-3 and ced-4, either within the cell or in a neighboring cell.

a. Trueb. False*

[64] In worms, mammals and fruit flies, the pathways that regulate the effector proteases that lead to naturally occurring apoptosis, share many of the same components, including

a. pro- and anti-apoptotic regulators*b. initiator proteasesc. regulatory IAP componentsd. identical gene-expressed activating factors

[65] Cell death may occur without DNA fragmentation, but it would still be identified with TUNEL labeling.

a. Trueb. False*

[66] Free radicals such as O2.- and mitochondrial flavoproteins (AIF)may be caspase-independent pathways for cell death.

a. True*b. False

[67] A neuron’s mitochondrion outer membrane becomes permeable and releases cytochrome c, AIF or Smac, causing the neuron to die. This is an example of

a. A caspase pathwayb. A caspase-independent pathway*c. An extra-cellular pathwayd. None of these

[68] In mammals, the Bcl-2 family of membrane-associated proteins a. Are pro-apoptoticb. Are anti-apoptoticc. Are mostly pro-apoptotic (12 to 5)*d. Are mostly anti-apoptotic (12 to 5)

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[69] Transgenic mice that overexpress the Bcl-2 protein, a. Have much bigger brains than controls*b. Have much smaller brains than controlsc. Have brains the same size as controls except that the facial nucleus and

retina display a 40% increase in neuron number d. Have brains the same size as controls except that the facial nucleus and

retina display a 40% decrease in neuron number

[70] The two major points in the nerve cell where regulation of apoptosis occurs are:

a. Mitochondrial membrane and at the caspases*b. At the caspases and the nerve cell’s outer membranec. At the nerve cell’s outer membrane and at the mitochondrial membraned. At the caspases and at the neurotrophins

[71] The inhibitors of apoptosis proteins (IAPs) serve as one of the so-called ‘safety latches’ on caspase activation; in Drosophila if three gene products (grim, reaper, hid) that inhibit IAP function are lost, what happens?

a. Unrestrained activation of caspases and cell deathb. Almost no detectable PCDc. Caspase activation is unaffected because of alternate pathway regulationd. Extensive release of cytochrome c from the mitochondrial membrane

[72] Experiments with C. elegans double mutants (both decreased killer gene function (weak ced-3) and a null engulfment gene) showed that

a. The double mutants displayed more surviving cells than single mutants with weak ced-3

b. Dying neurons may be able to recover unless they are engulfed and phagocytized

c. Single mutants with weak ced-3 displayed more surviving cells than non-mutants

d. All of these are correct*

[73] The movement of phosphatidylserine (PS) from the inner to the outer leaflet of the plasma membrane

a. Exposes PS so that microglia can recognize a dying cell*

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b. Is the normal movement of this transporter in a healthy cell c. Masks PS so that dying neurons do not become engulfedd. None of these are correct

[74] Contrary to the prediction that the formation of functional synapses influences the survival of the growing neuron by regulating trophic support, blocking synaptic transmission with an acetylcholine receptor antagonist in the chick embryo during the period of motor neuron death resulted in a dramatic decrease in motor neuron death.

a. True*b. False

[75] Studies of the effects of cochlear ablation on the number of cells in the nucleus magnocellularis in the chick central auditory system

a. Supported the hypothesis of afferent-regulated survivalb. Showed massive cell loss early in development and almost no cell loss laterc. Showed that the transition from massive cell loss to no cell loss may occur

in as little as two daysd. All of these are correct*

[76] In vitro studies of nucleus magnocellularis cells together with auditory nerve afferents, examined protein synthesis as a marker of potential cell death.

a. When auditory nerve was stimulated, protein synthesis was maintained in NM cells*

b. When NM axons were stimulated to produce antidromic action potentials in their cell body, protein synthesis was maintained in NM cells

c. When auditory nerve was stimulated, protein synthesis was not maintained in NM cells

d. None of these are correct

[77] The N-methyl D-aspartate (NMDA) receptor, is activated by the neurotransmitter, glutamate, and is permeable to calcium. In mice whose NMDA receptors are deleted transgenically,

a. Displayed dramatically increased Naturally occurring neuron deathb. Provided evidence for the role of calcium in neuron survival and deathc. Both of these are true*d. Neither of these are true

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[78] It is believed that calcium-dependent neuron survival happens because the entry of calcium into neurons causes an increase in BDNF expression.

a. True*b. False

[79] When cultures of embryonic cortex neurons are depolarized by adding KCl to the culture dish, calcium enters the neurons and

a. The level of BDNF expression increases and more neurons survive*b. The level of BDNF expression decreases and more neurons survivec. The level of BDNF expression increases and fewer neurons survived. The level of BDNF expression decreases and fewer neurons survive

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Elsevier · Web viewNT dimer binds to Trk, Trk dimerizes, ligand-receptor complex transphosphorylates tyrosine residues, adaptor proteins bind to phosphorylation sites, adaptor proteins