Astrocytes

What is the developmental origin of astrocytes, and how does this differ from microglia

Astrocytes derive from neural precursors (same origin as neurons and oligodendrocytes). Microglia are the exception — they migrate into the brain from the blood during embryonic development and are functionally related to peripheral macrophages

What is GFAP, and what does its upregulation indicate

GFAP (glial fibrillary acidic protein) is an intermediate filament protein expressed mostly in astrocytes. Upregulation indicates reactive astrogliosis — the astrocyte has become activated in response to injury, disease, or pathological stimuli

Name all four types of astrocytes and where each is found

1. Protoplasmic — most common; gray matter

2. Fibrous — white matter

3. Interlaminar — cell body in one cortical layer, branches cross into other layers; primates only

4. Varicose — deep layers; branches do NOT cross layers; primates onl

What is the key morphological difference between interlaminar and varicose astrocytes

Interlaminar: cell body in one layer, branches CROSS into other layers. Varicose: cell body and branches STAY within the deeper layers — no crossing. Both are found mainly in humans and non-human primates

What are the three components of the tripartite synapse

1. Presynaptic axon terminal

2. Postsynaptic dendritic spine

3. Astrocyte process The astrocyte is an active participant in synaptic transmission — not just a structural bystander

How many synapses can a single astrocyte contact, and what does this imply

Up to 100,000 synapses per astrocyte. This means a single astrocyte can simultaneously monitor and modulate a massive number of synapses, making astrocytes powerful regulators of neural circuit activity

What are the four key functions of astrocytes

1. Regulate blood vessel size and blood flow

2. Provide neurons with glucose for fuel

3. Release gliotransmitters (e.g., ATP) to communicate with neurons and other cells

4. Maintain the blood-brain barrier

What are gliotransmitters, and what is a specific example from the lecture

Gliotransmitters are signaling molecules released by astrocytes. ATP is the specific example given. Cells expressing ATP receptors (purinergic receptors) on their membranes can detect and respond to extracellular ATP released by astrocytes

What is AQP4, where is it located, and what is its function

AQP4 (Aquaporin-4) is a water channel concentrated at astrocyte endfeet that wrap around blood vessels. It regulates water movement between the brain and vasculature and is critical for the glymphatic system — the brain's waste clearance pathway.

What is the glymphatic system, and how do astrocytes contribute to it

The glymphatic system is the brain's waste clearance pathway — cerebrospinal fluid flows through perivascular spaces, flushing out toxic proteins like tau. Astrocyte AQP4 at endfeet drives this flow. Disruption (e.g., after TBI) allows toxic proteins to accumulate

What happens to AQP4 localization after TBI, and why is this harmful

AQP4 mislocalizes away from astrocyte endfeet after TBI. Since AQP4 at endfeet drives glymphatic clearance, its mislocalization impairs waste removal — allowing phosphorylated tau (P-Tau) and other toxic proteins to accumulate, worsening brain damage

What is reactive astrogliosis and what triggers it

Reactive astrogliosis is the activated state astrocytes enter in response to brain injury or disease. Triggers include TBI, neurodegeneration, and demyelination (as in MS). Signs include GFAP upregulation, cell hypertrophy, and morphological changes

ow are human astrocytes different from mouse astrocytes?

Human astrocytes are significantly larger and morphologically more complex than mouse astrocytes. This was demonstrated by transplanting human astrocytes into mouse brain. Greater complexity allows them to contact more synapses, potentially contributing to human cognitive capacity

How does the astrocyte's position — contacting both synapses and blood vessels — make it suited to link neuronal activity to blood flow

Astrocytes detect synaptic activity at one end (via glutamate uptake and receptors) and signal to blood vessels at the other end (via endfeet). This allows them to dilate/constrict vessels to match blood flow to local neural demand — the basis of neurovascular coupling

What do P-Tau and NeuN each mark in the Iliff 2014 TBI study

P-Tau (phosphorylated tau) = a microtubule protein in axons that becomes pathologically phosphorylated after injury — a marker of neuronal damage and tauopathy. NeuN = marker for neuronal cell bodies (soma). Used to assess neuronal survival after TBI