Glial Flashcards
What do they do?
It appears that there are no neuropathological processes that occur w/out participation of glial cells, specifically … & ….
What do they do?
It appears that there are no neuropathological processes that occur w/out participation of glial cells, specifically MICROGLIA & ASTROCYTES
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
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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
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
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
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
Lactate via … into axons, converted to …. by lactate ….., used by …. for …. …. - generation of ATP
Lactate via MCT2 into axons, converted to PYRUVATE by lactate DEHYDROGENASE, used by MITOCHONDRIA for OXIDATIVE PHOSPHORYLATION - generation of ATP
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
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
L1, page 18 & 19
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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)
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)
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
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
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
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
L1, page 24
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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)
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L2, page 4
- Look at a fibrous astrocyte & protoplasmic astrocyte
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Astrocytes
Protoplasmic - found in … matter
Fibrous - found in … matter
Radial glia - radially arranged in … …
Mechanical support, blood brain barrier, response to injury, …. …..
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
Protoplasmic astrocyte
- Many … or … proccess
- Respond to … ….
Protoplasmic astrocyte
- Many SHORT or LONG processes
- Respond to CHANGING ENVIRONMENT
Astrocyte distinguished by
Cytoplasm
- Well developed cytoskeleton
- Dominated by … ….
- Also … & …. / mitochondria
- Many …. …
Astrocyte distinguished by
Cytoplasm
- Well developed cytoskeleton
- Dominated by INTERMEDIATE FILAMENTS
- Also MICROTUBULES & ACTIN / mitochondria
- Many GAP JUNCTIONS
Astrocyte
- Astrocyte end-feet on …
Communicate via … waves
- … binding protein
…. …. channels and …. receptors
Release ….
Astrocyte
- Astrocyte end-feet on BVs
Communicate via Ca2+ waves
- Ca2+ binding protein
VOLTAGE GATED channels and NEUROTRANSMITTER receptors
Release GLIOTRANSMITTERS
Tripartite synapse
L2, page 9
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Astrocytes - active communication
- Release gliotransmitters via ….
- Ca2+ release from … ….
Astrocytes - active communication
- Release gliotransmitters via EXOCYTOSIS
- Ca2+ release from ENDOPLASMIC RETICULUM
Hemichannel
- Gap junction to release into …
Reflexive gap junction
- Gap junction onto …
Hemichannel
- Gap junction to release into ECS
Reflexive gap junction
- Gap junction onto ITSELF
L2, page 13
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Astrocytes and control of blood flow
Gap junctions b/w … & …
Astrocytes and control of blood flow
Gap junctions b/w ASTROCYTES & ENDFEET AT BV
What do astrocytes do?
- Astrocytes ensheath … contacts
- Astrocytes processes have … receptors
- Endfeet at BVs - have … connexin (Cx) expression
- Astrocytes release … ….
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
L2, Page 18
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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
Astrocytes in rat
L2, page 21
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Some complicated shit on L2, page 22
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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
Synchrony
L2, page 24
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Tripartite synapse
Detect … and influence other …
- Diagram on L2, page 25
Tripartite synapse
Detect ACTIVITY and influence other NEURONS
- Diagram on L2, page 25
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)
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
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
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
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
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
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
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
L3, page 22 & 23
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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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Microglia
L4, page 3
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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
L4, page 6-9
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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
L4, PAGE 11
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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
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
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
Maybe learn L4 page 17 - 29
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