L12 (C4) Flashcards
how many glia are there per neuron
1-2
Glial cells outnumber neurons in the human brain
Involved in almost all neural functions. what are some of these functions
Brain metabolism
Neuronal survival
Modulate synaptic activity
Communication
what are the key characteristics of neurons
they are excitable cells used for communication
there are 10^11 neurons and 10^14 synapses
they are post mitotic (meaning the neurons we had at birth we will have at death
they have a high metabolic rate (which is supported by glia)
what are the key characteristics of glia
they are not excitable however they can be stimulated by Ca in astrocytes
they main role is support, nutrition and glue but they can communicate with themselves and other neurons
there are 10x more glia than neurons and they make up 50% of the brains volume
they undergo mitosis (regenerate)
what do glia NOT have than neurons do
No chemical synapses,
action potentials,
neurotransmitters
but hey do have glial transmitters
what does oligodendrocytes mean
Greek: Oligos=few; Dendron= tree
tree like structure
what is the main role of oligodendrocytes
myelination and metabolic support
what are satellite oligodendrocytes
they are considered to be part of the gray matter whereas myelinated oligodendrocytes are part of the white matter
their role is to support metabolic function
how can the processes of the oligodendrocytes be recognised and distinguished from the
profiles of axons,
by their electron dense cytoplasm and their closely packed
microtubules.
what is the process of myelination
the order in which things get myelinated
15 - 16 months we have full milination
16 weeks is the starts of milneation
4-6 is he formation of the corpus callosum
Anterior cerebral hemispheres 7 -10 months
Occipital 9-12 months
Parietal 9-12
Temporal lobe 11-14
what was a key driver in evolution
myelination
what are the 4 reasons why myelination is an evolutionary advantage
- Myelination strongly reduces energy consumption
- Rapid impulse propagation/increased conduction velocity
- Muscle control
- Neurotrophic contribution
how is neurotrophic contribution an evolutionary advantage
required for the long-term integrity and survival of axon
how is muscle control an evolutionary advantage
became the basis for the development of complex predatory
and escape behaviour, which ultimately drove body size and vertebrate evolution
This means that we would be able to run faster/respond faster from things that were trying to kill us
how is rapid impulse propagation/increased conduction velocity an evolutionary advantage
allowed complex yet compact higher nervous systems to evolve.
makes APs 10x faster
how is myelination strongly reduces energy consumption an evolutionary advantage
action potentials and ion currents are restricted to less than 0.5% of the axon’s surface.
Myelin strongly reduces energy consumption because it is all focused at one point which also allows for rapid propagation and conduct velocity
what is the difference between myelinated axons in the CNS and the PNS
In the CNS this is the oligodendrocytes. One oligo can myelinate multiple internodes
The swann cells in the PNS only myenate one segment of one neuron
Therefore in the CNS myelination happens around more than one axon and in the PNS a schwann cell will only go around one but can be associated with many
why are very thin axons unmyelinated
In order to be myelinated the acon needs to have a diameter more than 1um because otherwise it won’t have an effect. Therefore small axons won’t be myelinated
naked axons are found where
in the CNS
why are unmyelinated axons in the CNS referred to as naked but unmyelinated in the PNS are not
In the PNS unmyelinated are still surrounded by membrane of the schwann cell. This is because thee swann cell needs to protect the axon therefore its membrane, although it is not completely covering it, they are associated
NOTE: PNS schwann cells are associated with many axons but you don’t completely encase the axon
why is it adventitious in the PNS to have schwann cells associated with many neurons
This is adventitious in the PNS as if one swann cell dies then it will only effect on axon where as in the CNS it will effect multiple
describe the structure of an oligodendrocyte
There is a inner cytoplasmic and a outer cytoplasmic ridge
When you cut away the myelin you can see that it comes in a bit in the nodes. This part is called the parra node
Oligodendrocytes have a wide reach
what causes myeline gene expression
NRG 1 type 3
how does NRG 1 type 3 cause myelin gene expression
When NRG 1 type 3 is expressed in the axon and when it recognised that then it starts a signal cascade cascade which causes myelin gene expression
what is the inner and the outer part of the myelin called
The inner mesaxon is the inner part of the membrane and the otter mesaxon is the outer part
what is important about the myelins thickness
The bigger the diameter the bragger the myelin sheath
if there are issues with the thickness it means means that there is a problem with that axon
what is the g ratio (thickness) for myelin wrapping
0.6 - 0.7
what is the equation for g ratio
g ratio = d/D
d = axon diameter
D = axon + myelin diameter
is remyelination of an axon possible
yes but the remyelination will never be as thick as it originally was
describe the process of lateral radial wrapping in oligodendrocyte myelination
The oligodendrocyte has a precursor cell
When it starts growing then it makes more plasma membrane and starts to ensheath the axon. It rolls around it. When it grows it gets wider and longer, this is lateral radial wrapping
While the wapping is happening then the channels become clustered in the nodes
The smitlansion incisures or clefts and these are the cytoplasmic channels which are there to deliver the proteins needed
You then have created the nodes
The incisures close but the incisures around the cleft are still there so it is able to keep growing if it is needed
what are The smitlansion incisures or clefts
The smitlansion incisures or clefts and these are the cytoplasmic channels which are there to deliver the proteins needed
what is the difference between oligodendrocyte and schwann cell myelination
oligodendrocytes have one extension which wrapps one part of one axon for many axons
Whereas schwann cells wrap one part of one axon
why do we need local protein synthesis in the oligodendrocytes
synthesis of myelin proteins needs to happen distal
to the cell body
what is needed for local protein synthesis to take place in the oligodendrocytes
microtubule based transport takes RNA granules that contain mRNA and ribosomes from the nucleus to the parranodes
what is the major dense line
MDL is the 2 inner layer of plasma membrane – a tiny bit of cytoplasm
toothpaste tube and the little bit of toothpaste left inside
what is the intraperiod line
IPL is the 2 outer layers of plasma membrane and ECS
the outside of the toothpaste tube and the space inbetween the layers
what proteins stop the myelin sheath from unrolling
P0 protein zero (PNS) located from cytoplasm to extracellular space (across the membranes) where it will bind to another PO protein
MBP myelin basic protein (PNS/CNS) only in the cytoplasm
PMP 22 peripheral myelin protein (22kD)
(PNS) transmembrane protein
describe the structure of the internodes
node -> paranodal region -> juxtaparanodal region -> internodeal region
where are the stabilising proteins located in the internode
the ones that stop the myelin sliding along the axon
in the paranodal and juxtaparanodal regions
what proteins stabilise the internode
the ones that stop the myelin sliding along the axon
NF155 - neurofascin – glial/axon cell adhesion molecule
Cntn/Cntn2 – contactin - cell adhesion – glial/axon
Caspr – transmembrane protein on axon – contactin-associated protein
what is the role of casper NF155 and Cntn/Cntn2
seals periaxonal
space to outside
what do we know about NF115
NF stands for neurofilament
I the parranode there is neurophassin this can be 155 or 165 as it is not just produced by the myelin sheath but also the axons
Therefor it goes through the space from the myelination and the axon to hold them together
where is casper produced
Casper is produced in the paranodal regions and it binds to neurophassin
what is casper associated with
Casper is also called contatic associated protein because they are always together and they bine to stabilise the paranodal section
At the juxtaparanodal region there are lots of different contactins and casper
what does casper bind to
neurophassin
what % of a myelinated axon is ensheathed in myelin
99%
when does the axon use nodally sourced energy
Nodally sourced energy is for basal activity or small-diameter
myelinated axons with short internodes as they only fire at low frequencies.
how will they get energy continually along the length of
internode or when demand increases?
through MCTs (monocarboxylate transporters )
these are extracellular
membrane channels which transport lactate, pyruvate, and ketone bodies, along with protons, down their concentration
gradient across membranes
how many MCTs (monocarboxylate transporters ) do we know of
there are 14 or more
how many MCTs (monocarboxylate transporters ) in the CNS
MCT1, 2 and 4 are in the CNS
which MCTs (monocarboxylate transporters ) is located in oligodendrocytes
MCT1
how do Oligodendrocytes uniquely provide metabolic support to neurons/axons
they carry molecules with one carboxylate group (monocarboxylates), e.g. lactate and pyruvate, across
biological membranes.
where are MCT1 and 2 located and how does their location get energy into the axon
MCT1- oligo plasma membrane
MCT 2 - axon plasma membrane under
Myelin
This is about getting energy into the axon, it gets it from the outside of the oligodendrocyte and brings it into the paraxonal space (1) and then from the space into the axon (2)
what is the principal
metabolic supplier of lactate to neurons an axons
oligodendrocytes
´Why is this important? Expression
of MCT1 reduced in motor
cortex of ALS patients
ALS = amyotrophic lateral sclerosis
what is ALS
amyotrophic lateral sclerosis
Expression
of MCT1 reduced in motor cortex of ALS patients which causes issues with voluntary movement
why do you want lactate in the oligodendrocytes
It can get latate from the blood or it can get glucose which it breaks down into lactate which is then converted to pyruvate by lactate dehydrogenase which is used by mitochondria for oxidative phosphorylation to make ATP
how does glucose get into the oligodendrocyte
through GLUT
what is the NMDA receptors role in the e metabolic supportive function of oligodendrocytes
The neuron releases glutamate into the synaptic cleft which binds to NMDA receptors on the oligodendrocyte which then sends a signal to transport lactate into the neurons
what is the effect of excessive NMDA signaling
Deleterious (damaging) effect of excessive NMDA receptor signaling in
oligodendrocytes is now
confirmed to be closely related with demyelinating white matter diseases, such as cerebral palsy,
multiple sclerosis, schizophrenia,
and Alzheimer’s disease
Multiple sclerosis
Guillain Barr syndrome (both autoimmune diseases) which involve disruption of myelin, loss of myelin. what does this cause
Changes in function (CNS and PNS)
Slowed nerve conduction because AP are not saltatory
this affects movement, bodily functions and causes loss of sensations, co-ordination, and balance
it also causes muscle weakness, difficulty with walking, Numbness and Visual disturbances
what does Multiple sclerosis refer to
sclerosis = scars
Multiple sclerosis refers to scars (sclerae- known as plaques or lesions) particularly in the white matter of the brain and spinal cord
this is from the immune system targeting the myelin
Multiple sclerosis causes…
Loss of oligodendrocytes, Microglia and Astrocytes
Degradation of myelin
Immune response- inflammatory response
when does onset of MS usually happen
20-40s
what is the initial cause of MS
Within the cellular system we have T cell which are not supposed to be in the brain.
Somehow they get into the brain
These express lots of cytokines which recruit other T cells and macrophages to attack
They also propagate they cycle of inflammation
It also causes the release of antibodies which means that the macrophage will attack the myelin sheath
every clinical episode of MS how many new plaques will they develop
10
what are some hypothesis for the cause of MS
people think that it could be from stress or about the latertude
Further away from the equator more common
there are 3 stages to MS damage what are these
- lymphocyte driven inflammation
- microglia activation
- chronic tissue injury (astrocytic gliosis)
what causes the microglia to be activated
the role of microglia are for inflammation and repair
at the start they removal of myelin debris and Promote remyelination
But: Chronic activation of microglia leads ultimately to neuronal loss in late stage (because of their inflammatory response)
