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Printable Handouts
Navigable Slide Index
- Introduction
- The functions of astrocytes in healthy CNS
- Astrocytes also respond to all forms of CNS injury and disease
- The understanding of astrocytes over the years
- Seminar outline
- Key features of astrocyte reactivity
- Astrocyte reactivity is heterogeneous and context dependent
- Astrocyte reactivity is heterogeneous
- Astrocyte reactivity is heterogeneous: summary of influences and responses
- How is astrocyte reactivity transcriptionally regulated?
- Astrocyte reactivity is associated with diverse transcriptional changes
- Transcriptional Regulators (TRs) of astrocyte reactivity
- Astrocyte reactivity differs in different disorders
- Observations of transcriptional changes
- Astrocyte reactivity and DNA-binding motifs
- Expression of TR protein in predicted TRs that do not have DNA-binding motifs
- Astrocyte disease differs from astrocyte reactivity
- Various forms of “diseased” astrocytes that can cell autonomously contribute to disease
- Divergent astrocyte reactivity TRs across multiple disorders
- Greater evidence for transcriptionally regulated loss-of-functions than gain-of functions
- Diseased astrocytes and detrimental effects in CNS disorders
- How can few TRs regulate many DEGs?
- TR regulation of astrocyte reactivity DEGs is combinatorial and complex
- Astrocyte reactivity regulation browser
- What do reactive astrocytes do?
- Two major categories of astrocyte reactivity: non-proliferative and proliferative
- Non-proliferative astrocyte reactivity may influence aspects of CNS ‘normal’ function
- Why do astrocytes proliferate & form borders around CNS lesions
- “Glial scars” have been blamed for the failure of CNS regeneration
- Our results, in contrast to expectation
- Additional findings
- Stimulated regeneration can occur robustly in spite of astrocyte borders (1)
- Stimulated regeneration can occur robustly in spite of astrocyte borders (2)
- Why do astrocytes proliferate & form borders around CNS lesions?
- Evidence for wound-repair border-forming astrocytes
- Newly proliferated astrocytes form borders
- Astrocytes proliferate to form borders around CNS wounds
- Why do astrocytes proliferate & form borders?
- Disruption of astrocyte borders
- Loss-of-function studies
- Astrocyte borders around non-neural cells in tissue lesions and astrocyte limitans borders
- Wound repair astrocytes proliferate & become transcriptionally reprogrammed
- Terminology: It is time to retire the term "glial scar"
- It is time to retire the term "glial scar"
- Conclusion
- Thank you for listening
Topics Covered
- Astrocyte reactivity and its effect on different disorders and contexts
- Regulating differences of astrocyte reactivity in various disorders
- Functions and effects in astrocyte reactivity
- Molecularly diversity and context dependency in astrocyte reactivity
- Contrasting the long standing dogma of scar tissue formation and axon regeneration prevention by reactive astrocytes
- Important functions of reactive astrocytes: regulating CNS inflammation, protecting neural tissue, and facilitating wound repair
Links
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Therapeutic Areas:
Talk Citation
Sofroniew, M. (2023, July 31). Astrocyte reactivity [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved November 21, 2024, from https://doi.org/10.69645/UPGZ8320.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Michael Sofroniew has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
A selection of talks on Neuroscience
Transcript
Please wait while the transcript is being prepared...
0:00
Hello my name is
Michael Sofroniew from
UCLA. Welcome to
this Henry Stewart
Talk on Astrocyte Reactivity.
0:12
Astrocytes are a main cell
type in the brain and
spinal cord where
they constitute
about 30-40% of the cells.
Astrocytes tile the entire
central nervous system
which we'll refer to as the CNS.
The image shows this tiling in
the mouse hippocampus
and cerebral cortex.
White dots represent
astrocyte nuclei
selectively stained for the
transcription factor Sox9
and shows that they are
evenly spaced throughout the
tissue. The green stain
is for GFAP which is
visible in the main
astrocyte branches in
the hippocampus but GFAP is not
detectably expressed by
cortical astrocytes
in healthy tissue.
Astrocytes are highly branched
cells and their branches
interact with multiple other
cell types, in particular
with neurons and synapses
where astrocytes contribute
many functions that
are essential for
maintaining and influencing
synapse function.
As shown in the schematic on
the right these functions
include taking up and
recycling neurotransmitters and
maintaining potassium
homeostasis.
Astrocytes also contact
blood vessels and
help to regulate
blood flow and
interstitial fluid levels
and lymphatic flow.
In addition, astrocytes form
an important border around
the entire surface of the brain
and spinal cord that separates
neural tissue from the non-neural
tissue of the meninges.
1:38
In addition to
their functions in
the healthy central nervous
system astrocytes respond
to all forms of injury
and disease with
changes that are referred
to as astrocyte reactivity.
These responses include
many variable changes
in gene expression and protein
expression as well as changes in
cell structure and potentially
also cell proliferation.
In histological tissue
sections as seen in
the images on this slide,
increased staining
for the protein GFAP is
a prototypical sign of
astrocyte reactivity.
This slide shows examples
of astrocyte changes in
various human disorders or
mouse models including
stroke, traumatic injury,
neurodegenerative diseases like
Alzheimer's disease, tumors,
autoimmune inflammatory diseases
like multiple sclerosis,
and their models and infections.