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anat242 > mod 2 > Flashcards

mod 2 Flashcards

1
Q

3 main elements of the cytoskeleton

A

microtubules, neurofilaments, microfilaments

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2
Q

microtubule structure

A

hollow tube of protein tubulin, large, 20nm, polarised made of beta and alpha tubulin dimers, oriented lengthwise

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3
Q

microtubule function

A

trafficking of proteins, vesicles, mitochondria

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4
Q

microtubule fast axonal transport

A

bidirectional

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5
Q

microtubule slow axonal transport

A

anterograde

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6
Q

kinesine

A

anterograde - transports things down end of axon

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7
Q

dyenin

A

retrograde - transports back to the soma

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8
Q

what drives polymerization/depoly within microtubules

A

GTP bound to beta tubulin

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9
Q

what does a tau protein do

A

stabilises microtubule and links one microtubule to the next

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10
Q

where are taus found

A

dendrite and axon inclu distal axon

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11
Q

where is MAP-2 found

A

soma and dendrite

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12
Q

what does anterograde transport

A

mitochondria, vesicles, membrane lipids

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13
Q

what does retrograde transport

A

used materials

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14
Q

motor domain

A

contains ATP, conserved across specied

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15
Q

tail domain

A

binds to specific cargoes, diverse across/within species

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16
Q

neurofilament structure

A

intermediate: neurofilament light, medium and heavy (NFL, NFM, NFH) 10 nm diameter

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17
Q

neurofilament function

A

structural framework, is most stable of cytoskeleton having huge mechanical strength

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18
Q

microfilaments structure

A

small, actin molecule, 5nm diameter.
dynamic positive barbed and negative pointed ends

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19
Q

actin tredmilling

A

a dynamic turnover of actin filament while filament length is maintained. get a new net flow of G-actin through filament

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20
Q

actin in presynaptic terminal

A

is enriched and regulates the vesicle pool

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21
Q

actin in postsynaptic terminal

A

regulate surface receptor diffusion and the exo-endocytic trafficking of receptors to surface

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22
Q

microfilaments function

A

endo/exocytosis as well as spine growth, strength

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23
Q

failure of axonal transport

A

leads to a number of different diseases, alzheimers, parkinsons, auto-immune, motor neuron

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24
Q

what does nisssl stain detect

A

RNA, dark staining represents large stacks of RER

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25
Q

technique to identify and locate proteins

A

immunohistochemistry

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26
Q

immunohistochemistry

A

primary antibodies bind to target antigen, secondary antibodies bind to primary antibody and also contains a fluorescent tag enabling protein to be identified

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27
Q

inside of cell membrane

A

hydrophobic

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28
Q

inside/outside of cell membrane

A

hydrophilic

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29
Q

cleft protein

A

trans-synaptic proteins, secreted presynaptically, cell adhesion molecules, interact with molecules on surface of adjacent cell

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30
Q

myosin

A

found in muscles, travel along actin

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31
Q

Fluorescence in situ hybridization (FISH)

A

use DNA probes to target different chromosomal locations

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32
Q

oligodendrocytes function

A

myelinates multiple axons

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33
Q

small diameter myelinated axons with short internodes fire at what frequencies

A

low

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34
Q

how much do action potentials and ion currents take of the axons surface

A

restricted to less than 0.5%

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35
Q

what do monocarboxylate transporters MCT in extracellular membrane channels transport?

A

lactate pyruvate and ketone bodies 14 or more MCTs

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36
Q

how do oligodendrocytes provide neurons with energy

A

carry molecules with one carboxylate group e.g. lactate and pyruvate across biological membranes

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37
Q

what is the metabolic supportive function of oligodendrocytes regulated by

A

glutamate binding to NMDA receptor

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38
Q

what is an NMDA receptor

A

glutamate - major excitatory neurotransmitter

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39
Q

deleterious effect of excessive NMDA receptor signalling

A

excitotoxicity

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40
Q

multiple sclerosis

A

destruction of myelination, oligodendrocyte/schwann cell dysfunction. scars refer to particularly in white matter of brain and spinal cord

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41
Q

microglia structure

A

small, high branched cells. 5-20% of all glia cells

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42
Q

how to identify microglia

A

immuno-cytochemical identification and Iba1-actin binding proteins

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43
Q

microglia function

A

defence function, synapse elimination, phagocytosis, homeostasis

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44
Q

distribution of microglia

A

large phenotypic diversity, more in grey matter, near synapses, concomitant with astrocytes

45
Q

response to injury

A

when they detect and intruder, they call for help by releasing cytokines which makes the BBB permeable. they become motile, apoptosis, phagocytic

46
Q

microglia neuronal functions

A

neurogenesis, induction + phagocytosis of apoptotic neurons, synaptic pruning

47
Q

microglia immune functions

A

phagocytosis, antigen presentation, pro/anti inflammatory response, immuno-surveilance through extra/intracellular receptors

48
Q

during what stage of development do microglial invade the CNS

A

late embryonic development, developing from haemopoietic cells of bone marrow

49
Q

microglia lifespan

A

lasts 20+ years, renewing slowly ~30% / year

50
Q

microglia resting

A

not moving, but ramified branched process survey the microenvironment

51
Q

microglia activated

A

amoeboid, move freely throughout neural tissue, phagocytose debris, pruning of cells/dendrites

52
Q

cytokines/inflammation synaptic and neural development

A

pruning and apoptosis

53
Q

growth factors synaptic and neural development

A

plasticity and neurogenesis

54
Q

what do microglia actively survey the environment with

A

pattern recognition receptors - e.g. toll-like receptors

55
Q

extracellular side of toll-like receptor

A

recognition of the microbial product

56
Q

cytoplasmic side of toll like receptor

A

TIR domain, recruit signalling molecules, alter kinase activation/transcription

57
Q

good microglia

A

ligand recognised, internalized, eliminated

58
Q

bad microglia

A

overactivated, produce cytotoxic factors

59
Q

overactivation of microglia

A

causes unknown, environmental toxins - pesticide can lead to neurodegenerative diseases like alzheimers.

60
Q

what happens to microglia in alzhiemers

A

their activation increases

61
Q

what happens to microglia in alzhiemers

A

their activation increases (bad)?. however the tau tangles produce cytokines which attract microglia

62
Q

neuotoxicity from overproduction of microglia do what to NADPH oxidase

A

cause neurotoxicity through activation of NADPH oxidase –> increased reactive oxygen species. this is activated in alzheimers and parkinsons

63
Q

ependymal cell structure

A

cuboidal, columnar shape, apical microvilli, cilia, contain intermediate filaments

64
Q

ependymal cell distrubtuion

A

line the ventricular system of CNS

65
Q

ependymal cell function

A

inflammatory response, trophic and metabolic support, secrete cerebrospinal fluid, regulator of osmotic pressure, control concentrations fo regulatory peptides, function as neural stem cells

66
Q

what did einstein have in abundance

A

astrocytes

67
Q

astrocytes structure

A

star shaped, long branched, dominated by intermediate filaments, microtubules, actin/mitochondria, gap junctions

68
Q

astrocytes function

A

communication, nutrient transport from blood to neuron, support myelin coverage of neurons

69
Q

how do astrocytes communicate

A

pick up and pass on information via calcium waves through Ca2+ binding protein

70
Q

astrocytes role in glutamate/glutamine

A

astrocytes uptake glutamate and GABA from neurons and then release glutamine for neurons to uptake

71
Q

activation of ionotropic glutamate receptors and metabotropic receptors

A

released from astrocytes to postsynaptic neurons to activate extrasynaptic NR2B - containing NMDA receptors to trigger slow inward currents

72
Q

how do astrocytes get energy

A

through blood flow

73
Q

vasodilation

A

glutamate receptors -> Ca transient travels to end-feet -> release of vasodilators

74
Q

distribution of astrocytes

A

numerous in grey matter, adjacent to blood vessels, in contact with synapses

75
Q

gap junctions of astrocytes

A

ensure minimal overlap, are between astrocytes and between end-feet at blood vessel

76
Q

hemichannel

A

gap junction to release into extra-cellular space

77
Q

reflexive gap junction

A

gap junction onto itself

78
Q

astrocytes three type of gap junctions

A

reflexive gap junction
intracellular gap junction
hemichannel gap junction

79
Q

astrocytic dysfunction in alzheimers disease

A

reactive astrocytes produce amyloid beta.
AB inhibits glutamate uptake, increasing Ca2+ signalling leading to abnormal vascular responses and inhibition of LTP and memory loss

80
Q

astrocytes and BBB

A

astrocytic end foot makes up part of BBB, interface between epithelial cells and rest of brain. if cells active, require more nutrition, they pump more lactate

81
Q

role of astrocytes during non-inflammatory conditions

A

one end at vasculature other end-foot on BBB, carries out neurotransmitter clearance and buffering of K+ and metabolic support

82
Q

astrocytes during inflammatory conditions

A

reactive astrocytes become branched and fuzzy, end-feet can detach from BBB and gap junctions break down. astrocytes respond by forming a scar

83
Q

astrocytes reponse in inflammatory conditions

A

moderate astrogliosis - more production of GFAP, which makes astrocytes get more branched and densely rigid

84
Q

role of reactive astrocytes for neuroprotection

A
  1. debris clearance
  2. BBB repair of leakiness
  3. glial scar as barrier
  4. secretion of anti-inflammatory factors
  5. sequestering of excess glutamate (glutamate excitatoxicity)
85
Q

3 ways to make reactive astrocytes

A
  1. resting astrocyte undergoes hypertrophy
  2. ependymal cell undergoes gliogenesis
  3. stem cell undergoes gliogenesis
86
Q

BBB structure

A

endothelial cells on inside, pericytes around, basal lamina matrix - fibrous around whole thing and astrocytic end-feet form third layer round the outside

87
Q

what makes the BBB really impermeable

A

tight junctions that form between endothelial cells

88
Q

glutamate from endothelial cells to astrocytes

A

glucose broken down into pyruvate –> to lactate –> further broken to acetylcholine to use internally within the astrocyte

89
Q

what mechanism allows for astrocytes and neurons to get lactase

A

MCT4 (astrocytes) MCT2 (neurons)

90
Q

what do astrocytes give oligodendrocytes to support synapse

A

monocarboxylate

91
Q

diffusion of BBB

A

lipid soluble agents like alcohol, nicotine, antidepressants

92
Q

protein transporters of BBB

A

glucose, amino acids, and more

93
Q

receptor-mediated transcytosis of BBB

A

insulin, transferrin, interleukins

94
Q

absorptive transcytosis of BBB

A

albumin, other plasma proteins

95
Q

efflux transporters of BBB

A

cetirizine

96
Q

paracellular transport of BBB

A

water soluble agents

97
Q

pericyes of BBB

A

regulates permeability and immune function

98
Q

tight junction of BBB composition

A

claudin and occludin

99
Q

if BBB gets leaky:

A

reative oxygen species, hypoxia and/or thrombin + fibrin

100
Q

hypoxia in BBB

A

when leaky, albumin leaks in –> edema –> capillary blood flow -> hypoxia

101
Q

reactive oxygen species in BBB

A

red blood cells leak into brain -> hemoglobin -> iron -> reactive oxygen species

102
Q

what causes leaky BBB

A

aging, radiation, stress, hypertenion, trauma, toxicants

103
Q

thing that strengthen BBB

A

diet, circadian rhythm, physical activity

104
Q

what can bacterial factors do to BBB

A

infiltrate the blood lumen

105
Q

changes to the bacterial factors in BBB

A

can upregulate inflammatory cytokine levels affecting integrity and promote neuroinflammation

106
Q

BBB role in multiple sclerosis

A

BBB gets dyregulatated

107
Q

BBB role in HIV and AIDS

A

damage to tight junctions of BBB allows macrophages to cross into brain leading to HIV encephalitis

108
Q

BBB role in alcoholism

A

exposure to ethanol injures the endothelial cells that form tight junctions in the BBB

109
Q

BBB role in alzheimers

A

AB accumulation -> BBB dysregulation -> decreased AB clearance across the BBB

anat242 (4 decks)

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