Glial

Question 1

What do they do?

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

Answer 1

What do they do?

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

Question 2

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

Answer 2

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Question 3

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

Answer 3

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

Question 4

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

Answer 4

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

Question 5

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

Answer 5

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

Question 6

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

Answer 6

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

Question 7

L1, page 18 & 19

Answer 7

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Question 8

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)

Answer 8

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)

Question 9

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

Answer 9

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

Question 10

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

Answer 10

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

Question 11

L1, page 24

Answer 11

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Question 12

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)

Answer 12

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Question 13

L2, page 4

• Look at a fibrous astrocyte & protoplasmic astrocyte

Answer 13

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Question 14

Astrocytes

Protoplasmic - found in … matter

Fibrous - found in … matter

Radial glia - radially arranged in … …

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

Answer 14

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

Question 15

Protoplasmic astrocyte
- Many … or … proccess

• Respond to … ….

Answer 15

Protoplasmic astrocyte
- Many SHORT or LONG processes

• Respond to CHANGING ENVIRONMENT

Question 16

Astrocyte distinguished by

Cytoplasm

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

Answer 16

Astrocyte distinguished by

Cytoplasm

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

Question 17

Astrocyte

• Astrocyte end-feet on …

Communicate via … waves
- … binding protein

…. …. channels and …. receptors

Release ….

Answer 17

Astrocyte

• Astrocyte end-feet on BVs

Communicate via Ca2+ waves
- Ca2+ binding protein

VOLTAGE GATED channels and NEUROTRANSMITTER receptors

Release GLIOTRANSMITTERS

Question 18

Tripartite synapse

L2, page 9

Answer 18

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Question 19

Astrocytes - active communication

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

Answer 19

Astrocytes - active communication

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

Question 20

Hemichannel
- Gap junction to release into …

Reflexive gap junction
- Gap junction onto …

Answer 20

Hemichannel
- Gap junction to release into ECS

Reflexive gap junction
- Gap junction onto ITSELF

Question 21

L2, page 13

Answer 21

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Question 22

Astrocytes and control of blood flow

Gap junctions b/w … & …

Answer 22

Astrocytes and control of blood flow

Gap junctions b/w ASTROCYTES & ENDFEET AT BV

Question 23

What do astrocytes do?

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

Answer 23

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

Question 24

L2, Page 18

Answer 24

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Question 25

Astrocytes product neuron - overexcitation Glutamate - major ... neurotransmitter Also a potent .... Glutamate cleared from EC space by .... .... transporters

Answer 25

Astrocytes product neuron - overexcitation Glutamate - major EXCITATORY neurotransmitter Also a potent NEUROTOXIN Glutamate cleared from EC space by HIGH AFFINITY transporters

Question 26

Astrocytes in rat L2, page 21

Answer 26

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Question 27

Some complicated shit on L2, page 22

Answer 27

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Question 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

Answer 28

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

Question 29

Synchrony L2, page 24

Answer 29

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Question 30

Tripartite synapse Detect ... and influence other ... - Diagram on L2, page 25

Answer 30

Tripartite synapse Detect ACTIVITY and influence other NEURONS - Diagram on L2, page 25

Question 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 .....

Answer 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) 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)

Question 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

Answer 32

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

Question 33

Potentiation of inhibitory synapses = .... & CA1 .... neuron Inhib interneuron releases ... at synapse - detected at .... astrocyte - interneuron keeps ... - Inhibitory input onto ... ... = ... .... via an astrocyte

Answer 33

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

Question 34

Synaptic plasticity - memory & learning Activity at one synapse affecting the .... of another synapse - ... range interaction .... the chance of it firing

Answer 34

Synaptic plasticity - memory & learning Activity at one synapse affecting the FIRING of another synapse - LONG range interaction INCREASE the chance of it firing

Question 35

Facilitating local LTP Heterosynaptic plasticity: Excitation at ... synapse - facilitate LTP at ... synapses eCB - ... .... signalling -> .... neuron -> ... ... interneuron - reduce .... release

Answer 35

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

Question 36

Synchronization of neurons by astrocytic glutamate release Astrocyte contacts a number of ... Results in ... ... of these neurons Known as a neuronal ...

Answer 36

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

Question 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

Answer 37

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

Question 38

EPILEPSY: In seizure foci in the hippocampus - astrocytes are different - Increased ... expression and ... ... communication - Increase spontaneous ... oscillations - inc. .... release astrocytes

Answer 38

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

Question 39

L3, page 22 & 23

Answer 39

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Question 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?

Answer 40

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Question 41

Microglia L4, page 3

Answer 41

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Question 42

Invade CNS in late embryonic development - Development from .... cells of bone marrow

Answer 42

Invade CNS in late embryonic development - Development from HAEMOPOIETIC cells of bone marrow

Question 43

L4, page 6-9

Answer 43

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Question 44

Microglia -> astrocyte dysfunction -> damage - Activation of .... - Release of .... - Impaired ... uptake - Activation of ... .... ... receptors - .... influx - Excitotoxicity - ... ....

Answer 44

Microglia -> astrocyte dysfunction -> damage - Activation of MICROGLIA - Release of MEDIATORS - Impaired GLUTAMATE uptake - Activation of POSTSYNAPTIC IONOTROPIC GLUT receptors - CA2+ influx - Excitotoxicity - NEURON DEATH

Question 45

L4, PAGE 11

Answer 45

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Question 46

Microglia - sense defunct ... and phagocytose them in normal brain via ..... Synaptic pruning by microglia is essential during development for the remodelling of ... ...

Answer 46

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

Question 47

Ependymal cells Line the ... system (VS) of ... .... - columnar shape - ... microvilli, cillia - contain ... filaments In specialized locations secrete ... ....

Answer 47

Ependymal cells Line the VENTRICULAR system (VS) of CNS CUBOIDAL - columnar shape - APICAL microvilli, cillia - contain INTERMEDIATE filaments In specialized locations secrete CEREBROSPINAL FLUID

Question 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 ... ...

Answer 48

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

Question 49

Maybe learn L4 page 17 - 29

Answer 49

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