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Neuro first semester 23-24 > Block I presentation Martins > Flashcards

Block I presentation Martins Flashcards

1
Q

what do schwann cells do?

A

Promote axonal regeneration and are derived from neural crest

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2
Q

What cells produce myelin in the CNS?

A

Oligodendrocytes

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3
Q

What cells produce myelin in the PNS?

A

Schwann cells

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4
Q

HOw much does a shwann cell myelinate?

A

1 shwone myelinates 1 PNS axon

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5
Q

How much does an oligodendrocyte myelinate?

A

Each oligo can myelinate many axons (~30)

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6
Q

What is the predominantly type of glial cell in white matter?

A

oligodendrocytes, derived from neuroectoderm

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7
Q

what structures are present in the sodium channels?

A

Nodes of ranvier

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8
Q

What are the main functions of the nodes of ranvier?

A

propagate action potentials via saltatory
conduction

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9
Q

What sodium channels are present in CNS and PNS

A

Nav1.2

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10
Q

what happens when there is maturation?

A

Nav1.3 is downregulated; while Nav1.6 compensates

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11
Q

What happens with sodium channels on early myelination?

A

co- localization of Nav1.2 and Nav1.6
clusters

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12
Q

What happens if spaces of node of ranvier are too big?

A

It dissipates

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13
Q

What is the node of ranvier?

A

Foot (non myelinated axon)

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14
Q

Microglia emerges from?

A

messenchymal

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15
Q

What protein is specific of PNS (hint electrophoresis)

A

Po; present in human and rat PNS electrophoresis

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16
Q

When does myelinization begin?

A

During the fetal period and continues during the first postnatal year

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17
Q

When does myelinization tends for be complete?

A

around the same time be complete the fibers
become functional

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18
Q

Which fibers myelinate first?

A

motor fibers > SENSORY FIBERS

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19
Q

What is the main purpose of myelin?

A

increase the conduction of speed of
electrical signals between neurons while reducing energy requirements

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20
Q

Where do oligodendrocytes emerge from?

A

stem cells/ectoderm

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21
Q

What myelin protein is present in both CNS and PNS?

A

MBP, pero hay mas en la CNS

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22
Q

What protein is from CNS exclusively?

A

MOG

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23
Q

What structure is myelinized last?

A

Forebrain

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24
Q

What structure is myelinized first?

A

spinal cord

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25
Q

When does myelinization of forebrain starts?

A

13-14 years; decision making social skills

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26
Q

myelinization final stops by?

A

~30 years

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27
Q

How much does myelin increase conduction?

A

6 times more

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28
Q

Multiple sclerosis?

A

CNS

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29
Q

Guillian barre?

A

PNS

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30
Q

What are the steps of myelinization of axonal nerves?

A
  • Glia polarization
  • Expansion and compaction of myelin.
  • Separation of axoplasm from extracellular milieu (nutrient deprivation bc it closes)
  • Glia support axonal energy Metabolism.
  • Gap junction linkage of local stacks of non-compacted myelin.
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31
Q

What are Schimdt Lanterman incisures? (SLI)

A

a circular-truncated cone shape in the
myelin internode that is a specific feature of myelinated nerve fibers formed in Schwann cells in the peripheral nervous system (PNS).

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32
Q

What are the functions of the SLI?

A

serving as a cytoplasmic channel
connecting the inner and outermost aspects of the myelin sheath, formation and structural stability of myelin, regulation of adhesion, and
signal transduction.

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33
Q

Where are sodium channel located?

A

Nodes of ranvier

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34
Q

Explain the Na channels

A

When Na channels are inrefractory period they are closed and inactivated, when an axon potential comes they open and depolarize, closing thus, opening K channels influx

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35
Q

What is Multiple sclerosis?

A

Chronic disease that damages the nerves
in the white matter of the CNS and spinal
cord.

Does not involve peripheral nerves
(5%).

Immune system attacks myelin Optic
nerve lesions are common.

Scarring of tissue in response to the
nerve damage.

Symptoms: problems with muscle
control, balance, vision, or speech.

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36
Q

What is Experimental allergic encephalomyelitis (EAE)?

A

Used as experimental model for
investigation of demyelination.
* Immunopathology and neuropathology
mechanisms leads to key pathological
features of MS: inflammation,
demyelination, axonal loss and gliosis in
the CNS.
* May occur following viral infections or
vaccinations (i.e. post infectious
encephalomyelitis).

generates cytokines and kills macrophages; model to destroy myelin

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37
Q

WHat is Guillian barre symptom?

A

Autoimmune disease: attack peripheral nerve myelin (Schwann cell myelination).
* Onset of disorder: fear and anxiety.
* Symptoms: pain, muscle weakness and paralysis, weakness of breath muscles.
* Diagnosis: rapid development of muscle paralysis, absence of reflex, CSF fluid analysis, nerve conduction studies, blood tests (not due to low blood K+ levels).

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38
Q

How many markers does oligodendrocytes have?

A

5-100, O4

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39
Q

What is S100?

A

Specific marker for schwann cell

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40
Q

What is the composition of BBB?

A
  1. endothelial cells lining the capillary wall with tight junctions between them.
    (2) processes of astrocytes abutting on the capillaries as perivascular end-feet.
    (3) a capillary basement membrane.
    (4) pericytes
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41
Q

what is the function of the BBB?

A

The blood-brain barrier (BBB) is the specialized system of brain microvascular endothelial cells
(BMVEC) that shields the brain from toxic substances in the blood, supplies brain tissues with nutrients, and filters harmful compounds from the brain back to the bloodstream.

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42
Q

Why are endothelial cells different from peripheral cells?

A

because of tight junctions, transport system,

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43
Q

WHta quantity does not pass through the pericyte?

A

more than 500 dalton

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44
Q

What proteins are present in the basement membrane of bbb?

A

Collagen IV, Lamins, agrin

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45
Q

What is present on an endothelial cell?

A

Tight junctions and increased density of mitochondria

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46
Q

Which protien is the most important?

A

Claudin IV

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47
Q

Describe the basement memebrane of bbb

A

The BM is a sheet-like ECM (extracellular matrix) complex beneath epithelium
and endothelium.

At the BBB, the BM encircles the abluminal side of blood vessels and is located
at the interface of the circulation system and central nervous system

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48
Q

of what major proteins does the Basement membrane consist?

A

collagen IV, laminin, nidogen, perlecan,
and agrin

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49
Q

Which proteins have heparan sulfate proteoglycan?

A

Perlecan and agrin

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50
Q

What differentiates endotehlial cells of intracerebral vessels?

A

reduced density of caveolae and the presence of circumferential tight junctions between endothelial cells and increased density of mitochondria

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51
Q

What substances can pass through endothelium?

A

wide range of lipid-soluble molecules can diffuse through the endothelium and enter brain passively

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52
Q

Which molecules pass the endothelium more easy?

A

Bases, which carry a positive charge, have an advantage over acids in penetration of endothelial cells and it is probably the cationic nature of these molecules and an interaction with the negatively charged glycocalyx and phospholipid head groups of the outer leaflet of the cell membrane that facilitates their entry

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53
Q

What type of transport does the Transcellular bidirectional transport across cerebral endothelium occur?

A

receptor-mediated transport, carrier-mediated transport, ion transport, peptide transport, and active efflux transport.

54
Q

What does carrier-mediated transport facilitates?

A

transport of nutrients into brain including hexoses (glucose, galactose)

neutral, basic and acidic amino acids, and monocarboxylic acids (lactate, pyruvate, ketone bodies)

nucleosides (adenosine, guanosine, uridine)

purines (adenine, guanine), nucleotides,
nucleobases, organic anion, and organic cations; amine and vitamins

55
Q

How much claudins are there?

A

4 transmembranal proteins

56
Q

Where are claudins present?

A

Zona occludens

57
Q

Where are tight junctions present?

A

Tight junctions are present at the apical end of the interendothelial space being intimately connected to and dependent on the cadherin
based adherens junctions which are located near the basolateral side of the interendothelial space

58
Q

What do tight junctions prevent passing?

A

tracers such as HRP horseradish peroxidase

59
Q

What hydrophilic molecules can pass in tight junctions?

A

sodium, hydrogen, bicarbonate, and other ions

60
Q

gate or barrier?

A

Tight junctions

61
Q

What is the fence function?

A

Tight junctions also restrict the movement of membrane molecules between the
functionally distinct apical and basolateral membrane surfaces

62
Q

HOw many paralle strands are in tight junctions?

A

8-12 with no discontinuities

63
Q

Describe claudins`

A

Claudins are 18–27-kDa tetraspan proteins with a short cytoplasmic Nterminus, two extracellular loops, and a COOH terminal cytoplasmic domain which ends in valine

64
Q

Which are considered the main structural components of intramembrane strands and recruit occludin to tight junctions?

A

Claudins

65
Q

Which claudin regulates size-selective diffusion of small molecules?

A

Claudin 5, increased paracellular permeability to molecules <800D

66
Q

Where are tight junctions located?

A

cholesterol-enriched regions along the plasma
membrane associated with Cav-1.

67
Q

Of what have studies demonstrated that tight junctions are composed of?

A

an intricate combination of tetraspan and single-span transmembrane and cytoplasmic proteins linked to an actin-based cytoskeleton that allows these junctions to seal the paracellular space while remaining capable of rapid modulation and regulation

68
Q

What are the two tetraspan trasnmembrane proteins?

A

Claudin family and occludin

69
Q

Which is the single-span transmembrane protein?

A

junction adhesion molecule (JAM) family of proteins.

70
Q

What do the tetraspan proteins form?

A

form the paracellular permeability barrier and
determine the capacity and the selectivity of the paracellular diffusion pathway

71
Q

Describe occludin

A

a 60 kDa protein, participates in forming and maintaining the barrier between adjacent cells and acts as a fence to restrict movement of lipids and proteins between the apical and lateral domains

72
Q

Where occludin present?

A

present in most occluding junctions

73
Q

Do all edothelial cells have occludin?

A

No, but possess well-developed and fully functional zonulae occludentes

74
Q

is occludin required for assembly of intramembrane strands ate tight junctions?

A

no, its a regulatory protein

75
Q

What are JAMs?

A

Junctional adhesion molecule (JAM) is a 40 kDa protein that belongs to the immunoglobulin superfamily (IgSF).

76
Q

What is the fucntion of JAM?

A

It is responsible for increasing the electrical resistance of the cell membrane, thereby reducing paracellular permeability

involved in the formation of occluding junctions in endothelial cells as well as between endothelial cells and monocytes migrating from the vascular space to the connective tissue

77
Q

With what protein is JAM asociated?

A

not itself form a zonula occludens strand but is instead associated with claudins.

78
Q

WHat happens if there is overexpression of JAM?

A

Overexpression of JAMs in cells that do not normally form tight junctions increases their resistance to the diffusion of soluble tracers, suggesting that JAM functionally contributes to permeability control

79
Q

What are PDZ-domain proteins?

A

zonula occludens proteins ZO-1, ZO-2, and ZO-3

80
Q

Functions of PDZ

A

Regulatory functions during the formation of the zonula occludens have been suggested for all ZO proteins. In addition, ZO-1 is a tumor suppressor, and ZO-2 is required in the epidermal growth factor– receptor signaling mechanism. The ZO-3 protein interacts with ZO-1 and the cytoplasmic domain of
occludins.

81
Q

What does Evans blue do?

A

Attaches to albumin so that albumin does not pass to the brain

82
Q

What are some finctions of microglia?

A
  1. Immune role in CNS
  2. Maintain central homeostasis
  3. Combat disease: neuroprotective role
    (microglia>phagocytic macrophages)
  4. Development (promote axonal growth and migration)
  5. Comprise 10-20% of total glia cells in adult
  6. Contain neurotransmitter receptors
    7.Important feature: polarization [M0-resting; M1- inflammatory; M2-anti-inflammatory
83
Q

What is the M1 marker?

A

iNOS

84
Q

What is the M2 marker?

A

Arginase I

85
Q

What is caveolae?

A

can open both the luminal and albuminal plasm.

Intracerebral cortical vessels contain a mean of 5 caveolae/mm2 in arteriolar and
capillary endothelium a membrane through a neck 10–40 nm in diameter

Cerebral endothelium contains 14-fold fewer vesicles as compared with endothelium of
nonneural vessels such as myocardial capillaries. The decreased number of vesicles
in cerebral endothelium implies limited transcellular traffic of solutes in steady states

86
Q

What happens in capillaries in areas where bb is absent?

A

such as the subfornicial organ and area postrema, are highly permeable and have significantly higher numbers of endothelial caveolae

87
Q

Functions of caveolae

A

vesicular trafficking in transcytosis of proteins, endocytosis, and potocytosis

regulate a wide variety of signaling molecules.

function in the regulation of cell cholesterol and glycosylphosphatidylinositol (GPI)-linked proteins, in cell migration, as docking sites for
glycolipids and as flow sensors

Endothelial caveolae are involved in endocytosis, a process by which the permeant
molecules are internalized within endothelial cells or they may be involved in transfer of
molecules from blood across the cell to the interstitial fluid or in the reverse direction, a
process termed transcytosis

88
Q

What transport depends on ATP? And what is its inhibitor?

A

Both endocytosis and transcytosis may be receptor-mediated or fluid phase and require
ATP and can be inhibited by N-ethylmaleimide (NEM), an inhibitor of membrane fusion

89
Q

What is the molecular structure of caveolae?

A

generally accepted as a lipid raft.

membrane is enriched in b-d-galactosyl and b-N-acetylglucosaminyl residues in palmitoleic and stearic acids and in cholesterol and sphingolipids (sphingomyelin and glycosphingolipid).

90
Q

What is the function of sphingolipids?

A

substrates for synthesis of a second intracellular messenger, the ceramides

91
Q

What molecules provides support for caveolae?

A

Cholesterol provides a structural support for caveolae and creates the frame in which many caveolar molecules are inserted.

92
Q

Which caveolae are expressed in endothelial cells of the brain?

A

Cav-1 and 2

93
Q

Which caveolae are expressed in astrocytes?

A

Cav-3

94
Q

What are the isoforms of cav-1?

A

a and b and brain cells express predominantly the a -isoform

95
Q

WHta is cav-1?

A

the specific marker and major component of caveolae, is an integral membrane
protein (21–24 kDa) having both amino and carboxyl ends exposed on the cytoplasmic
aspect of the membrane (30).

96
Q

What is transcytosis?

A

a multistep process that involves successive caveolae budding and fission from the plasma membrane, translocation across the cell, followed by docking and fusion with the opposite plasma membrane

97
Q

What transcytosis processes does caveolae take part?

A

vesicleassociated membrane protein-2 (VAMP-2),

monomeric and trimeric GTPases, annexins II and IV, N-ethyl maleimide (NEF)-sensitive fusion factor (NSF), and its attachment protein – soluble NSF attachment protein (SNAP) and vesicle-associated SNAP receptor (v-SNARE).

98
Q

Technique used to measure paracellular transport?

A

Sucrose in brain serum

99
Q

Which receptors are invovled in receptor mediated transcytosis?

A

lipoprotein, epidermal growth factor, tumor
necrosis factor, albumin, transferrin, melanotransferrin, lactoferrin, ceruloplasmin,
transcobalamin, advance glycation end products, leptin, and insulin, all of which are
essential in maintaining cell and tissue homeostasis and are therefore referred to as
the life receptors

100
Q

what other factors are present in receptor mediator trasncytosis?

A

death receptors which are involved in cell apoptosis and include receptors for p75 and interleukin-1.

101
Q

What is the technique to measure transcytosis?

A

albumin in brain serum

102
Q

What is an Efflux transport?

A

Active efflux transport involves a transporter, which utilizes ATP to shuttle drugs and other solutes out of the brain and into the blood compartment

103
Q

What do efflux do with drugs?

A

minimize effective drug penetration into
brain parenchyma, thus limiting the efficacy of
drugs targeted at brain diseases

104
Q

What is the substrate in efflux transport?

A

verapamil

105
Q

P-gp transport potential was evaluated by

A

quantifying 3Hverapamil accumulation in the brain in proportion to that in the perfusate.

106
Q

What organs lack BBB?

A

Circumventricular organs, in the midline of the ventricular system; pineal, subcommissural organ, area postrema, pituitary gland, median eminence, organum vasculosum, subfornical organ

107
Q

Why do circumventricular organs lack bbb?

A

Discontinuous tight junctions between endothelial cells allow entry of molecules

108
Q

mention some strategies for delivering therapeutic treatments across the bbb?

A

Paracellular difussion: ultrasound and hyperosmotic agents

Trancellular pathway:
-drug modification:
1. lipidization
2. targeting moieties attachment
-carrier-based delivery:
1.nanoparticles
2.cells

109
Q

What do astrocyte end feet do?

A

provide structural integrity to the cerebral vasculature

110
Q

Explain brain metabolism

A

2% of body weight
20% energy demand
25% glucose

111
Q

What does the body use during brain development and in the adult during prolonged fasting periods

A

ketone bodies

112
Q

WHat hapens during prolonged fasting> (5-6 weeks)

A

ketone body levels rise significantly and are able to contribute almost 60% of the brain’s
energy requirement, thereby replacing glucose as the main fuel

113
Q

What does the body use during increased physical activity?

A

Lactate

114
Q

How is glut-1 present in the brain?

A

as 2 distinct molecular forms with molecular weights of 55- and 45-kDa, which are encoded by the same gene and differ only in their extent of glycosylation.

115
Q

where is the 55-kDa isofrom of glut1 detected?

A

detected exclusively in brain endothelial cells

116
Q

where is the 25-kDa isofrom of glut1 detected?

A

expressed in neurons and glial cells

117
Q

What is Glut1DS?

A

Glucose transporter type 1 deficiency syndrome (Glut1DS) is a rare genetic metabolic
disorder characterized by deficiency of a protein that is required for glucose to cross the blood-brain barrier and other tissue barriers. need keto diet to survive

118
Q

What do neurovascular and neurometabolic couple do?

A

enhance blood flow and utilization of metabolites in areas of neural activity

119
Q

What increases in localized regions of activity following neuronal stimulation?

A

Cerebral blood flow (CBF), blood volume, glucose consumption and oxygen
metabolism

120
Q

What is the gatekeepoer of neurological function?

A

claudin-5

121
Q

BBB impairment

A

Meningitis, alzheimer, MS, peilepsy, Stroke, parkinson, brain tumor, Schizophrenia, HIV encephalitis

122
Q

Hypoxic

A

insufficient oxygenation

123
Q

Ischemic

A

insufficient blood-flow

124
Q

Anemic

A

insufficient hemoglobin

125
Q

Lack of energy =

A

electrical failure

126
Q

Last long enough =

A

arrest of cellular functions and cell death

127
Q

Steps of hypoxia

A

First result of energy depletion:
failure of sodium and potassium pumps

Depolarization

Glutamate release

Overactivation of non-selective
cation-permeable ion channels >
Cl- passive influx into cells (osmotic
edema and rapid death)

128
Q

Hypoxia/ischemia of endothelial cells result in?

A

Angiogenesis and vascular remodeling

Increased vascular permeability

129
Q

Hypoxia/ischemia of basement emembrane cells result in?

A

Angiogenesis and vascular remodeling

Edema and hemorrage formation

130
Q

Hypoxia/ischemia of astrocytes cells result in?

A

Edema and hemorrage formation

Increased vascular permeability

131
Q

Hypoxia/ischemia of tight junctions result in?

A

Increased vascular permeability

132
Q

Hypoxia/ischemia of pericytes result in?

A

Increased vascular permeability

decreased vascular stability

Neuro first semester 23-24 (9 decks)

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