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Glial Flashcards

1
Q

What do they do?

It appears that there are no neuropathological processes that occur w/out participation of glial cells, specifically … & ….

A

What do they do?

It appears that there are no neuropathological processes that occur w/out participation of glial cells, specifically MICROGLIA & ASTROCYTES

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2
Q

Specific L1 objectives and more

  • To be able to describe the key structural features of oligodendrocytes
  • To be able to discuss the role of oligodendrocytes in maintaining neuronal energy supply
  • Be able to describe the consequences of glial cell dysfunction
A

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3
Q

MCT1 - … plasma membrane MCT1

MCT2 - … plasma membrane under myelin

Belong to a family of plasma membrane ….

  • Carry molecules with one carboxylate group (….), eg lactate & pyruvate, across biological membranes
A

MCT1 - OLIGO plasma membrane MCT1

MCT2 - AXON plasma membrane under myelin

Belong to a family of plasma membrane TRANSPORTERS

  • Carry molecules with one carboxylate group (MONOCARBOXYLATES), eg lactate & pyruvate, across biological membranes
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4
Q

Myelinated axons

Myelin sheath barrier from …. …, glucose from ….

  • …. substrates enter into the axon at … … ….
  • Diffusion times from the node to the internode could take many … for larger calibre …. with long internodes. These distances are critical
  • ATP consuming …. pumps and axonal …. mainly localized in …. regions
  • Nodally sourced energy - for … activity or small-diameter myelinated axons with short internodes - fire at … frequencies
  • Large myelinated axons firing … frequency
A

Myelinated axons

Myelin sheath barrier from EXTRACELLULAR, glucose from BVs

  • ENERGY-RICH substrates enter into the axon at NODES OF RANVIER
  • Diffusion times from the node to the internode could take many MINUTES for larger calibre AXONS with long internodes. These distances are critical
  • ATP consuming Na/K pumps and axonal MITOCHONDRIA mainly localized in INTERNODAL regions
  • Nodally sourced energy - for BASAL activity or small-diameter myelinated axons with short internodes - fire at LOW frequencies
  • Large myelinated axons firing HIGH frequency
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5
Q

Lactate via … into axons, converted to …. by lactate ….., used by …. for …. …. - generation of ATP

A

Lactate via MCT2 into axons, converted to PYRUVATE by lactate DEHYDROGENASE, used by MITOCHONDRIA for OXIDATIVE PHOSPHORYLATION - generation of ATP

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6
Q

How does the oligo/Schwann cell know the axon needs energy?

Experimental evidence
- Functional expression of …. receptors in mature oligodendrocytes, their processes and the myelin sheath

A

How does the oligo/Schwann cell know the axon needs energy?

Experimental evidence
- Functional expression of NMDA receptors in mature oligodendrocytes, their processes and the myelin sheath

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7
Q

L1, page 18 & 19

A

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8
Q

Lactate, a product of glycolysis, has been shown to play a key role in the …. support of neurons/axons in the … by both … & … through …. transporters (MCTs)

A

Lactate, a product of glycolysis, has been shown to play a key role in the METABOLIC support of neurons/axons in the CNS by both ASTROCYTES & OLIGODENDROCYTES through MONOCARBOXYLATE transporters (MCTs)

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9
Q

Olidgodendrocytes supply energy (lactate) to axons
- Implications for neuropathology

Demonstrate ‘dying-back’ neuropathy
- Suggests early … of axon function - due to lack of …, axonal transport failure - more distant from soma more vulnerable

A

Olidgodendrocytes supply energy (lactate) to axons
- Implications for neuropathology

Demonstrate ‘dying-back’ neuropathy
- Suggests early FAILURE of axon function - due to lack of ENERGY, axonal transport failure - more distant from soma more vulnerable

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10
Q

Dysfunction of Oligodendrocytes

Multiple system atrophy (MSA) - clinically degrees of parkinsonian, autonomic, and cerebellar features

  • Main feature - …. accumulation
  • a-synuclein - coded by … gene
  • major constituent of .. … in parkinsons disease
  • Predominantly … based
A

Dysfunction of Oligodendrocytes

Multiple system atrophy (MSA) - clinically degrees of parkinsonian, autonomic, and cerebellar features

  • Main feature - A-SYNUCLEIN accumulation
  • a-synuclein - coded by SNCA gene
  • major constituent of LEWY BODIES in parkinsons disease
  • Predominantly GENETICALLY based
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11
Q

L1, page 24

A

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12
Q

L2 objectives

  • To describe the basic form of an astrocyte
    • The key structural features of astrocytes
    • Importance of specific structures for function
  • Discuss how and why astrocytes communicate
  • Be able to discuss that astrocytes are very important cells in the brain. (using examples)
A

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13
Q

L2, page 4

  • Look at a fibrous astrocyte & protoplasmic astrocyte
A

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14
Q

Astrocytes

Protoplasmic - found in … matter

Fibrous - found in … matter

Radial glia - radially arranged in … …

Mechanical support, blood brain barrier, response to injury, …. …..

A

Astrocytes

Protoplasmic - found in GREY MATTER matter

Fibrous - found in WHITE MATTER matter

Radial glia - radially arranged in WHITE MATTER

Mechanical support, blood brain barrier, response to injury, METABOLIC SUPPORT

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15
Q

Protoplasmic astrocyte
- Many … or … proccess

  • Respond to … ….
A

Protoplasmic astrocyte
- Many SHORT or LONG processes

  • Respond to CHANGING ENVIRONMENT
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16
Q

Astrocyte distinguished by

Cytoplasm

  • Well developed cytoskeleton
    • Dominated by … ….
    • Also … & …. / mitochondria
    • Many …. …
A

Astrocyte distinguished by

Cytoplasm

  • Well developed cytoskeleton
    • Dominated by INTERMEDIATE FILAMENTS
    • Also MICROTUBULES & ACTIN / mitochondria
    • Many GAP JUNCTIONS
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17
Q

Astrocyte

  • Astrocyte end-feet on …

Communicate via … waves
- … binding protein

…. …. channels and …. receptors

Release ….

A

Astrocyte

  • Astrocyte end-feet on BVs

Communicate via Ca2+ waves
- Ca2+ binding protein

VOLTAGE GATED channels and NEUROTRANSMITTER receptors

Release GLIOTRANSMITTERS

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18
Q

Tripartite synapse

L2, page 9

A

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19
Q

Astrocytes - active communication

  • Release gliotransmitters via ….
  • Ca2+ release from … ….
A

Astrocytes - active communication

  • Release gliotransmitters via EXOCYTOSIS
  • Ca2+ release from ENDOPLASMIC RETICULUM
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20
Q

Hemichannel
- Gap junction to release into …

Reflexive gap junction
- Gap junction onto …

A

Hemichannel
- Gap junction to release into ECS

Reflexive gap junction
- Gap junction onto ITSELF

21
Q

L2, page 13

22
Q

Astrocytes and control of blood flow

Gap junctions b/w … & …

A

Astrocytes and control of blood flow

Gap junctions b/w ASTROCYTES & ENDFEET AT BV

23
Q

What do astrocytes do?

  • Astrocytes ensheath … contacts
  • Astrocytes processes have … receptors
  • Endfeet at BVs - have … connexin (Cx) expression
  • Astrocytes release … ….
A

What do astrocytes do?

  • Astrocytes ensheath SYNAPTIC contacts
  • Astrocytes processes have GLUTAMATE receptors
  • Endfeet at BVs - have HIGH connexin (Cx) expression
  • Astrocytes release VASOACTIVE METABOLITES
24
Q

L2, Page 18

25
Astrocytes product neuron - overexcitation Glutamate - major ... neurotransmitter Also a potent .... Glutamate cleared from EC space by .... .... transporters
Astrocytes product neuron - overexcitation Glutamate - major EXCITATORY neurotransmitter Also a potent NEUROTOXIN Glutamate cleared from EC space by HIGH AFFINITY transporters
26
Astrocytes in rat L2, page 21
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27
Some complicated shit on L2, page 22
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28
Astrocytes influences neuronal response Glutamate release - Activates ... .... receptors - Activates ... receptors - astrocyte Gluatamate release from astrocyte to post-synaptic neuron - Activates NR2B-containing ... receptors to trigger ... inward currents (SICs) in .... CA1 neurons - Changes .. ... - Does this in many nearby synapses to help .... them
Astrocytes influences neuronal response Glutamate release - Activates IONOTOPIC GLUTAMATE receptors - Activates METABOTROPIC receptors - astrocyte Gluatamate release from astrocyte to post-synaptic neuron - Activates NR2B-containing NMDA receptors to trigger SLOW inward currents (SICs) in PYRAMIDAL CA1 neurons - Changes MEMBRANE POTENTIAL - Does this in many nearby synapses to help SYNCHRONIZE them
29
Synchrony L2, page 24
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30
Tripartite synapse Detect ... and influence other ... - Diagram on L2, page 25
Tripartite synapse Detect ACTIVITY and influence other NEURONS - Diagram on L2, page 25
31
Astrocytes -> neural function in CA1 region of the hippocampus - Draw a diagram of the alteration of strength of synaptic transmission and label where facilitation and inhibition occurs - L3, page 11 1) .... released from axon - ... on astrocyte - astrocytic - ... wave transmitted through cell - Astrocyte releases ... - ATP - converted to .... - depresses activity at .....
Astrocytes -> neural function in CA1 region of the hippocampus - Draw a diagram of the alteration of strength of synaptic transmission and label where facilitation and inhibition occurs - L3, page 11 1) GLUTAMATE released from axon - GLuR on astrocyte - astrocytic - Ca2+ wave transmitted through cell - Astrocyte releases ATP - ATP - converted to ADENOSINE - depresses activity at SYNAPSE (2)
32
Excitation and synchronization of adjacent neurons = bridging .... .... neural circuits Astrocytes releases .... Glutamate is sensed ..... by two .... neurons Generation in these two neurons of .... ..... ..... currents
Excitation and synchronization of adjacent neurons = bridging NON-DIRECTLY CONNECTED neural circuits Astrocytes releases GLUTAMTE Glutamate is sensed SIMULTANEOUSLY by two CONTIGUOUS neurons Generation in these two neurons of SYNCHRONOUS NMDAR-DEPENDENT EXCITATORY currents
33
Potentiation of inhibitory synapses = .... & CA1 .... neuron Inhib interneuron releases ... at synapse - detected at .... astrocyte - interneuron keeps ... - Inhibitory input onto ... ... = ... .... via an astrocyte
Potentiation of inhibitory synapses = INTERNEURON & CA1 PYRAMIDAL neuron Inhib interneuron releases GABA at synapse - detected at NEIGHBOURING astrocyte - interneuron keeps FIRING - Inhibitory input onto PYRAMIDAL = FEEDBACK POTENTIATION via an astrocyte
34
Synaptic plasticity - memory & learning Activity at one synapse affecting the .... of another synapse - ... range interaction .... the chance of it firing
Synaptic plasticity - memory & learning Activity at one synapse affecting the FIRING of another synapse - LONG range interaction INCREASE the chance of it firing
35
Facilitating local LTP Heterosynaptic plasticity: Excitation at ... synapse - facilitate LTP at ... synapses eCB - ... .... signalling -> .... neuron -> ... ... interneuron - reduce .... release
Facilitating local LTP Heterosynaptic plasticity: Excitation at ONE synapse - facilitate LTP at NEARBY synapses eCB - RETROGRADE ENDOCANNABINOID signalling -> POSTSYN neuron -> GABAergic interneuron - reduce GABA release
36
Synchronization of neurons by astrocytic glutamate release Astrocyte contacts a number of ... Results in ... ... of these neurons Known as a neuronal ...
Synchronization of neurons by astrocytic glutamate release Astrocyte contacts a number of NEURONS Results in NEURONAL SYNCHRONIZATION of these neurons Known as a neuronal DOMAIN
37
Epilepsy - dec Kir channels - uptake ... reduced - Reduction of ... & .... protein is observed in human epilepsy - Enhanced ... levels are observed in epileptic tissues and mights amplify ... release from astrocytes
Epilepsy - dec Kir channels - uptake K+ reduced - Reduction of EAAT1 & EAAT2 protein is observed in human epilepsy - Enhanced mGluR levels are observed in epileptic tissues and mights amplify GLUTAMATE release from astrocytes
38
EPILEPSY: In seizure foci in the hippocampus - astrocytes are different - Increased ... expression and ... ... communication - Increase spontaneous ... oscillations - inc. .... release astrocytes
EPILEPSY: In seizure foci in the hippocampus - astrocytes are different - Increased Cx43 expression and GAP JUNCTIONAL communication - Increase spontaneous Ca2+ oscillations - inc. GLUTAMATE release astrocytes
39
L3, page 22 & 23
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40
L4 objectives Structure and function of microglia - Basic structure and range of forms - Function - the good and the bad Ependymal cells as stem cells - Adult neurogenesis - Where, when, how much?
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41
Microglia L4, page 3
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42
Invade CNS in late embryonic development - Development from .... cells of bone marrow
Invade CNS in late embryonic development - Development from HAEMOPOIETIC cells of bone marrow
43
L4, page 6-9
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44
Microglia -> astrocyte dysfunction -> damage - Activation of .... - Release of .... - Impaired ... uptake - Activation of ... .... ... receptors - .... influx - Excitotoxicity - ... ....
Microglia -> astrocyte dysfunction -> damage - Activation of MICROGLIA - Release of MEDIATORS - Impaired GLUTAMATE uptake - Activation of POSTSYNAPTIC IONOTROPIC GLUT receptors - CA2+ influx - Excitotoxicity - NEURON DEATH
45
L4, PAGE 11
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46
Microglia - sense defunct ... and phagocytose them in normal brain via ..... Synaptic pruning by microglia is essential during development for the remodelling of ... ...
Microglia - sense defunct SYNAPSES and phagocytose them in normal brain via FRACTALKINE Synaptic pruning by microglia is essential during development for the remodelling of SYNAPTIC CIRCUITS
47
Ependymal cells Line the ... system (VS) of ... .... - columnar shape - ... microvilli, cillia - contain ... filaments In specialized locations secrete ... ....
Ependymal cells Line the VENTRICULAR system (VS) of CNS CUBOIDAL - columnar shape - APICAL microvilli, cillia - contain INTERMEDIATE filaments In specialized locations secrete CEREBROSPINAL FLUID
48
Neural stem cells - cells that .... and are ... giving rise to neurons and glia The production of new functional neurons in the adult brain: ONLY in: - Subventricular zone of ... ... - Subgranular zone of ... ...
Neural stem cells - cells that SELF-RENEW and are MULTIPOTENT giving rise to neurons and glia The production of new functional neurons in the adult brain: ONLY in: - Subventricular zone of LATERAL VENTRICLE - Subgranular zone of DENTATE GYRUS
49
Maybe learn L4 page 17 - 29
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ANAT242 (6 decks)

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