L13 Flashcards

(59 cards)

1
Q

describe microglia

A

they are small cells (smallest glia cell) which are highly branched

each normally own domain (15-30µm)

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2
Q

what % of glial cells do microglia make up

A

5-20%

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3
Q

how are you able to identify microglia

A

whith

Immuno-cytochemical identification

Iba1 - actin binding proteins

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4
Q

what are the functions of microglia

A

homeostasis – routinely monitor extracellular environment

activity dependent synapse elimination

phagocytosis of surplus neural precursor cells

defence function -> normal (-> exacerbate inflammation)

many roles in disease processes

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5
Q

describe the distribution of microglia

A

Varies dependent on region

Greater in grey matter

Around synapses

With astrocytes

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6
Q

where do microglia stem from

A

development from haemopoietic cells of bone marrow (therefore they have the same generation as other immune cells)

Myeloid origin (not ectodermal)

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7
Q

when do microglia (MG) invade the CNS

A

in late embryonic development

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8
Q

describe the shape of MG

A

they have a variable shape depending on the arrangement of the actin cytoskeleton

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9
Q

what is Iba1 (actin binding protein 1) involved in

A

shape changes of the MG

We used this to identify microglia and it is involved in them dividing

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10
Q

are microglia able to divide

A

yes

Renew slowly at a median rate of 28% per year, and some
microglia last for more than two decades.

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11
Q

describe the ultrastructure of MG (what they would look like in an electron micrograph)

A

elongated nuclei “bean” shaped
with peripheral heterochromatin

scattered cisternae of rough endoplasmic reticulum and Golgi
complexes at both poles

a microglial cell is adjacent to a neuron there is usually a thin astrocytic process

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12
Q

the microglia cells form depends on its function

what are the 2 forms that they can have

A

resting and activated

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13
Q

describe the resting state of MG cells

A

Resting (not moving)
but Ramified (branched) processes survey the
microenvironment (Surveying microglia),

Maintain a constant level of available microglia to
rapidly detect and fight infection

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14
Q

describe the activated state of MG cells

A

also known as Ameoboid

free movement throughout the neural tissue as it is scavenging,
phagocytose debris,

this is also the state in Development/pruning

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15
Q

what are the 3 reasons we are interested in MG function

A

we are interested in their

resting/servalent state

ability to detect injury

response to injury

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16
Q

why are we interested in MG resting state

A

we are interested in their ability to …

sense the condition of the extracellular milieu

synaptic pruning and developmental apoptosis, neurogenesis

assessing synapses

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17
Q

why are we interested in MG ability to detect injury

A

we want to know more about receptors in the microglial cell membrane and how they initiate the process of active response

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18
Q

why are we interested in MG cells response to injury

A

we are interested in the….

synthesis and release of chemokines – attract other microglia

Proliferation or entry of monocytes via BBB (often faulty in disease)

Become motile, apoptosis, phagocytic

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19
Q

how often is the entire volume of the brain surveyed by microglia cells

A

every 4-5 hours

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20
Q

Microglia actively survey and shape
neuronal circuit structure and function

why is this important

A

for homeostasis of the synapses

surveillance, pruning, phagocytosis, synaptic plasticity

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21
Q

what are some examples of neurological disorders that MG are associated with

A

OCD and retts syndrome

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22
Q

what is Apoptosis

A

Apoptosis is the process of programmed cell death

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23
Q

what 2 things have effects on synaptic and neural development

A

cytokines/inflammation factors and growth factors

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24
Q

what is the effect of cytokines/inflammation factors on synaptic development

A

synaptic pruning

25
what is the effect of cytokines/inflammation factors on neural development
apoptosis
26
what is the effect of growth factors on synaptic development
synaptic plasticity
27
what is the effect of growth factors on neural development
neurogenesis (formation of new neurons)
28
what happens when a single protein in microglia is disrupted
If there is a mutation then it can reach out to grap the protein but it wont be able to pull it in and engulf it
29
how do the microglia affect neurotransmission and synaptic plasticity
It affects basal neurotransmission and synaptic plasticity by releasing soluble factors They also act on astrocytes
30
what is fraktaline signaling
Fractalkine signaling happens via soluble fractalkine that is released by the neurons and the glia have the fractaline receptors for it This is how the neuron and the microglia talk to each other This modulates the microglial synappes interactions to effect LTP (long term potentiation)
31
how do microglia know what syannapes to phagocytose
via fractalkine signaling
32
what are the implications in neurogenesis for healthy MG
phagocytosis of apoptotic and dysfunctional progenitors support progenitor migration synaptic mantaniace secretion of trophic factors fine tuned fractalkine signaling pathway
33
what are the consequences on neurogenesis from pathologically activated MG
impeared phagocytosis of apoptotic and dysfunctional progenitors dysfunctional progenitor migration failure of synaptic mantaniace secretion of cytotoxic factors deregulated fractalkine signaling pathway
34
Microglia actively survey the environment with pattern recognition receptors (PRRs). what do these receptors detect
That recognise molecular patterens of pathogens
35
what do toll like receptors recognise
bacterial lipids and viral DNA
36
describe the toll like receptors (TLR) and what each side does
Extracellular side of TLR-recognition of the microbial product Cytoplasmic side of TLR - TIR domain - recruit signalling molecules - alter kinase activation / transcription factors - > Modify gene expression
37
what is the overall response to TLR activation
Tailors immune response to the specific pathogen | causing inflammation / defense
38
why do microglia also have receptors for neurotransmitters
They also have receptors for neurotransmitters eg NMDA and AMPA sol they can limit the inflammatory environment so it doesn't interfere with the synapps
39
what happens when MG become overactivated
they produce cytotoxic factors which are (in high doses) neurotoxic
40
when MG are overactivated they produce cytotoxic factors which are neurotoxic what are some examples of these
Superoxide, nitric oxide, tumour necrosis factor-α
41
Causes of MG overactivation are not well understood what could be some reasons as to why this happens (2 reasons)
in response to environmental toxins - pesticide many neurodegenerative disease cause overactivation of many microglia - eg Alzheimer’s disease, microglial activation increases as disease progresses
42
when do MG produce reactive oxygen species
when toll like receptors are activated
43
why would MG make reactive oxygen species
because it is important for cell signaling
44
what happens when reactive oxygen species get too high
microglial apoptotic cell death or – too much proinflammatory gene expression causing neurotoxicity NOTE: overactivity ROS acts extracellularly
45
Toxins can cause neurotoxicity through activation of the NADPH oxidase -> which leads to increased ROS (reactive oxygen species) what are some examples of these toxins
Lipopolysaccahride (E coli), paraquat (chemical herbicide), MPTP (synthetic heroin -> acute Parkinsonian symptoms), amyloid beta, thrombin etc.
46
in what diseases is NADPH oxidase activation to produce ROS
Alzheimer’s disease Parkinson’s disease Involved in the neural damage in response to cerebral vascular dysfunction
47
how do MG cause astrocytic dysfunction
The ROS inhibits the glutamate transporters in the astrocytes therefore it is not being mopped up. This causes problems to the neurons as extra glutamate will bind to extracellular/extrasynaptic receptors increasing Ca influx at the synappes leading to excitotoxicity neuron cell death
48
Air pollution is an environmental factor that causes activation of MG what does this cause
prenatal air pollution exposure - increased risk of neurodevelopmental disorders – eg autism spectrum disorder (ASD). increased inflammatory cytokine protein altered the morphology of microglia, = activation or a delay in maturation, only male mice - this was because there was increased overlap between MG and neurons when offspring was prenatally exposed to DEP NOTE: Diesel exhaust particles (DEP)
49
how could targeting MG be a potential treatment of AD
TAU attracts the immune cells APOE collects inside MG transforming them into their activated form causing them to attack the neurons as well If you can limit the microglia when they are in there activated form (late in the disease process) can stop then from killing the neurons (stop it from getting worse)
50
what causes the overactivation of MG in AD
They found that there was a inituall stage change in gene expression and then there is a decrease in the immune checkpoints causing them to become more of a phagocytosis factor
51
why do we want to understand gene expression on MG
Gene expression can show how MG switch states in disease If we can understand the gene expression then we can target the diseased microglia
52
where are ependymal cells found
They line the fluid filled cavities of the brain They are within the ventricle and the choroid plexus villi forms the CSF
53
what do ependymal cells form
a barrier between the brain and the CSF
54
describe the structure of ependymal cells
Cuboidal - columnar shape with apical microvilli, cilia they also contain intermediate filaments
55
what are some functions of ependymal cells (5 roles)
Brain-CSF barrier and filter Inflammatory response A regulator of osmotic pressure Control the concentrations of regulatory peptides control CSF flow Trophic and metabolic support In specialized locations secrete cerebrospinal fluid Function as neural stem cells, (self-renewal and multipotency)?
56
how do ependymal cells control CSF flow
They do it by recovery stroke
57
what is brain washing
We have brain washing when the brain washes itself with new CSF This helps clear the brain of the toxic waste
58
how often does brainwashing occur
The brain is rinsed every 20 min
59
how do ependymal cells provide Trophic and metabolic support
There are several growth factors in the ependymal cells and there are particular regions in the brain where they can make CSF as well but majority of their role is for movement