The lectures will cover the function of glia in neuroscience.
The slides are available online.
Rules of engagement:
Communication is encouraged.
Ask questions if anything is unclear.
The lectures present the state of the art, not universal truth.
Alternative explanations will be provided.
It is up to the student to elaborate with additional reading.
The lecturer may be wrong about some things.
Take notes and ask questions.
To challenge the neurocentric view and highlight the importance of glia.
To give examples of why glia are the somewhat forgotten cells when we understand the complexity and the function of the brain.
Many historical and contextual reasons exist for the neurocentric view of neuroscience.
The lecturer's hidden purpose is to inspire interest and passion for glia.
Development of different glial cell types and their lineages.
Interconnection of glial cell development with brain development.
Specific functions of each glial cell type.
Relevance of glial cell dysfunction in brain disorders.
Methods used in glial research differ from those used in neuron studies.
Action potential recordings are not common in glial research.
The lecturer will explain the methods used in glial research.
Understand the development of glia, including timing and steps.
Understand the functions of glia in the brain environment, both in steady state and in the adult and aging brain.
Identify critical molecules and steps for the specification of specific glial cells.
Explore the role of glia in aging and disease.
Explore diseases particularly linked to the function of a given glial cell type.
The content will be continued in the neurodegenerative diseases module next year.
This module covers pieces not only for glia but for just generally neurodegenerative diseases.
Microglia ethics tissues name: means the opposite.
Microglia: a specific type of glial cell.
Glia: everything that is not microglia.
Glial cells essential for development and function neurons, despite not carrying synaptic input.
Neurons comprise only 10% of cells in the central nervous system, while glia make up 90%.
The high percentage of glia suggests their critical role in brain function.
In the peripheral nervous system, Schwann cells are the main glial cell type.
In the central nervous system:
Microglia constitutes 10-15% of glia.
Astrocytes are the majority within microglia.
Ependymal cells and oligodendrocytes are also present.
Astrocytes are the most abundant cells in the brain.
Provide physical support to neurons.
Supply nutrients and oxygen to neurons.
Insulate neurons, facilitating synaptic communication.
Destroy and remove cell debris and waste.
Critical developmental roles.
Participate in global migration.
Participate in the growth and direction of axons and dendrites.
Modulate synaptic transmission directly (astrocytes) or indirectly (microglia).
Critical role in brain disease and degeneration.
The percentage of glia increases with the complexity of brain function across species.
Glia to neuron ratio is unbalanced, with more glia in complex brains.
Astrocytes in humans are larger than those in rats, allowing for greater signal integration.
The increase in neuron size is not proportional to the increase in the size of the astrocyte.
The period of 70 years is considered the golden age of glial research.
Discoveries were driven primarily by improvements in technology.
Being a neuroscientist meant being an anatomist, using staining techniques and microscopy.
Rudolf Virchow (1856) first described glia, calling them glue (glia in Greek).
Otto Dieter described functional characteristics, noting the lack of axons in glia.
Debate focused on developmental origin, with Dieter suggesting a similar origin to neurons.
Subdivision of glia into different types occurred, with varying theories on their origin.
Ramón y Cajal postulated different types of glia from the ectoderm, identifying a third element.
del Río-Hortega challenged Ramón y Cajal, proposing four types of glia.
Proposed two types of glia in white matter and one in grey matter.
Identified mesodermal microglia.
Named them microglia for the first time, and he said that they would derive from the mesoderm.
He called another type of glia, which is what we know these days as oligodendrocytes.
This contradicted Ramón y Cajal, causing him to leave Spain until his discoveries were proven correct.
Functions such as plasticity, electrical insulation, and roles in pathology were attributed to glia.
After this golden era, there was a gap in glial research until the 1980s and 1990s.
From the 2000s onward, glia research regained attention due to the significant knowledge gap.
Based on historical perspectives, the ectoderm gives rise to the neuroepithelium, which forms the brain.
From the neuroepithelium, neuroblasts give rise to neurons.
Glial blasts were thought to have bipotent capacity to generate astrocytes and oligodendrocytes.
The neuroepithelium also generates ependymal cells.
Astrocytes can specialize into different types depending on brain region and function.
Microglia were believed to derive from the mesoderm, originating from a missing old cell in the janitor.
These entered the brain and completed the picture.
It is uncertain whether all cells derive from a single astrocyte progenitor.
The diversity of astrocyte states is not fully understood.
In what is known: Microglia do not derive from the mesoderm- acc primitive myeloid progenitors?
In the central nervous system:
Oligodendrocytes
Astrocytes
Microglia
Ependymal cells are also present.
In the peripheral nervous system, Schwann cells are the main type.
They follow a very similar developmental stepwise development as oligodendrocytes do.
Satellite cells are glial-like cells in the dorsal root ganglion.
Brain and embryo development involves complex interactions between organs and systems.
Embryonic layers (ectoderm, mesoderm, endoderm) differentiate into various organs.
The embryo is connected to the yolk sac, which is important for glial cell development.
Myelination and synaptic pruning continue into late life.
Glia become important when neurons start connecting, except for microglia, which arrive earlier.
Microglia arrive around eight weeks post-conception, before the blood-brain barrier closes.
The neuroepithelium generates neuronal stem cells and glial stem cells.
These stem cells share a common progenitor, allowing for the generation of both glia and neurons.
Radial glia, found in layered structures like the cortex, serve as a scaffold for neurons.
Radial glia also have the ability to generate astrocytes.
A neuroepithelial stem cell (e.g., radial glia) can generate any cell in the brain.
From that stem cell, you will generate what is called an oligodendrocyte progenitor.
From an oligodendrocyte progenitor, it will start to cycle, it will start to replicate, and the cells that it will produce will be terminally differentiated into astrocytes.
The oligodendrocyte progenitor converts into an NG2 cell (expressing NG2 molecule).
NG2 cells persist into the adult brain and can reactivate to produce mature oligodendrocytes.
NG2 progenitors transition to immature oligodendrocytes (losing NG2 expression, expressing O4).
Immature oligodendrocytes progress to a mature oligodendrocyte state.
Mature oligodendrocytes express myelin proteins like GC or MBP.
Transcription factors like Notch1 and Prox1 regulate these transitions. when lose expressiob if notch1 get increase of prox1
The NG2 cells express high levels now survive into the adult brain and they can produce more astrocytes.
Notch1
Prox1
Schwann cells are related to oligodendrocytes, sharing functions in the peripheral nervous system.
They develop similarly, starting from neuroepithelial cells to Schwann cell precursors and immature Schwann cells.
There are myelinating and non-myelinating Schwann cells.
Myelinating Schwann cells contain the axon within their cytoplasm and wrap it with extensions.
Non-myelinating Schwann cells provide trophic support for neighboring axons and neurons.
Astrocytes transition from neural stem cell progenitors to astrocyte precursors and mature astrocytes.
Mature astrocytes express proteins essential for function, such as GFAP.
Specific pathways define these transitions, with Sox9 essential for stem cell to astrocyte precursor transition.
Activation of the Jak-Stat pathway is critical for terminal differentiation.
There is functional and morphological heterogeneity in astrocyte populations.