Astrocytes Flashcards
List the main glial cells of the vertebrate brain
Astrocytes:
- largest and most abundant glial cells in the CNS.
- regulate neuronal environment, participate in synaptic activity, and maintain the blood-brain barrier.
Oligodendrocytes:
- responsible for myelinating axons in the CNS, increasing conduction velocity
- one oligodendrocyte can myelinate multiple axons.
Microglia:
- resident immune cells of the CNS, involved in clearing debris, phagocytosis, and inflammatory responses
- respond rapidly to injury or infection
Ependymal Cells:
Line the brain’s ventricles and spinal cord’s central canal
- produce and circulate cerebrospinal fluid (CSF) via cilia
Schwann Cells:
- found in the peripheral nervous system (PNS)
- myelinate single axons or support multiple unmyelinated axons.
Satellite Cells:
- surround neurone cell bodies in PNS ganglia, regulating the microenvironment
Describe the morphological features of astrocytes:
Star-shaped morphology - characterised by highly branched processes radiating from the soma
End-feet:
- specialised extensions contact
- blood vessels, forming a sheath
- neurones, synapses, and nodes of Ranvier
Intermediate Filaments -composed of glial fibrillary acidic protein (GFAP), a hallmark marker for astrocytes
Heterogeneity - morphology varies by brain region and function (e.g., protoplasmic astrocytes in gray matter vs. fibrous astrocytes in white matter)
Relationship to Other Cells:
- act as intermediaries between neurones and the vasculature
- influence and regulate neuronal activity, synapse formation, and ion homeostasis
Describe the physiological functions of astrocytes in the CNS:
Homeostasis:
- regulate extracellular K+ levels during neuronal activity preventing excitotoxicity
- buffer pH and maintain osmotic balance
Energy metabolism:
- store glycogen, metabolised to lactate, which is shuttled to neurones as an energy source
- critical during high metabolic demand
Neurotransmitter regulation:
- uptake of excess glutamate and GABA from synaptic clefts
- convert glutamate into glutamine, returned to neurones for recycling
Synaptic modulation:
- release gliotransmitters like ATP, D-serine, and glutamate, influencing synaptic activity
Immune role - secrete cytokines and chemokines in response to injury
Describe the role of astrocytes in neurotransmission:
Tripartite Synapse:
- astrocytes, presynaptic and postsynaptic neurones form a functional unit
- regulate synaptic strength by releasing gliotransmitters like ATP and D-serine
Neurotransmitter recycling:
- prevent excitotoxicity by uptaking glutamate through excitatory amino acid transporters (EAATs)
- Glutamate-Glutamine Cycle:
- Astrocytes convert glutamate to glutamine, sent back to neurones
Describe astrocytes role in metabolism:
Energy shuttle:
- convert glycogen into lactate for neuronal use
- support axonal metabolism during periods of intense activity
Oxidative Stress response:
- supply antioxidants (e.g., glutathione precursors) to protect neurones
Define neuroplasticity and identify the roles of astrocytes in this phenomenon:
Neuroplasticity is the capacity of the CNS to alter its structure, connections and function in response to internal or external stimuli and entails both functional and structural changes
Roles:
- release trophic factors e.g., brain-derived neurotrophic factor, or BDNF) to promote synaptic growth
- regulate turnover of dendritic spines
- influence long-term potentiation (LTP) and long-term depression (LTD) through gliotransmitters
- facilitate synaptic formation and stabilisation during development and learning
Recognise the contribution of astrocytes to synaptic pruning and describe how they identify target synapses
Pruning is the removal of weak or non-functional synapses performed by astrocytes in collaboration with microglial cells
Target identification - use complement proteins ( C1q and C3) to tag weak or inactive synapses for elimination
Mechanism - express receptors (MEGF10, MERTK) to engulf and degrade synaptic debris via phagocytosis
Functional significance - refining neuronal circuits during development and adapting to experience
Outline the role of astrocytes in regulation of vascular function in the CNS:
What is the blood brain barrier ?
- Located at vascular endothelial cells of cerebral vasculature.
- CNS neurons intolerant of peripheral blood metabolites, proteins, and immune mediators.
- Controls concentration of active neurotransmitters like glutamate.
- Can withstand destructive actions of immune cells and inflammatory mediators.
- Has mechanisms to identify and exclude toxic chemical species.
- Essential nutrients and metabolites cross the barrier using specific solute transporters.
- Active transport transports amino acids, facilitated diffusion crosses glucose.
- Strategy: no accidental crossing.
Describe astrocytes role in maintenance and functioning of the blood brain barrier:
Induction of tight junctions:
- release factors like VEGF, sonic hedgehog (Shh), and TGF-β to promote endothelial tight junction formation
Maintenance:
- end-feet provide structural support, regulate ion transport, and facilitate nutrient delivery
Selective permeability:
- modulate the exchange of metabolites and block harmful substances (e.g., pathogens, toxins)
Describe neurovascular coupling and the neurovascular unit:
Neurovascular coupling:
- NVC is a complex cross-talk between neurones, astrocytes, and blood vessels
- astrocytes monitor neural activity
- also mediate vessel contraction and dilatation using vasoactive agents like nitric oxide and prostaglandins
- match local cerebral blood flow (CBF) to neuronal energy demands
Neurovascular unit:
- comprises neural processes, astrocytic end-feet and the vascular cells (endothelial cells, pericytes and smooth muscle cells)
- level 1 is capillaries and pre capillary arterioles
- level 2 is parenchymal arterioles
- level 3 plial arterioles
Discuss the embryonic origin of astrocytes and growth potential in injury and disease
Development:
- astrocytes originate from neural stem cells in the ventricular zone during embryogenesis
- their differentiation is guided by Notch and BMP signalling pathways
Reactive astrocytes:
- proliferate in response to CNS damage (gliosis)
- form glial scars that limit injury spread but impede axonal regeneration
Role in Neurodegenerative disease:
- Contribute to pathologies like Alzheimer’s disease by dysregulating neurotransmitters or failing to maintain homeostasis
