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