glial cells Flashcards
what are the 4 glial cells?
astrocytes
oligodendrocytes
microglia
ependy,a;
where do astrocytes, oligodendrocytes and neurons orginate from?
neural stem cells in the ventricular and subventricular zones in the embryo
where do microglia originate from?
peripheral macrophage-like cells which migrate into the CNS
what is a common feature of all glial cells?
they are not electrically excitable, which means they cannot generate action potentials
cajal and astrocytes
- noted existance of large/principal cells (neurons) and cells that connected to these principal cells and blood vessels
- these cells often showed a star shaped body so were named astrocytes
types of astrocytes
- protoplasmic
- fibrous
- radial (bergman glia)
where are protoplasmic astrocytes found?
grey matter
where are fibrous astrocytes found?
white matter of brain and spinal cord
where are radial astrocytes found?
predominantly located in regions like the ventricular zone and the subventricular zone during brain development
characteristics of astrocytes
- small size of their cell body (typically <10micrometres)
- numerous (often hundred) of thin (<1micrometres) hair-like processes which spread in all directions and infiltrate all spaces between neurons
processes of astrocytes
- do not propagate APs and TF lack specialisation
- no axons or dendrites in astrocytes
- most located in grey matter spread their processes in all directions (protoplasmic) but there are also polarised aysmmetric astrocytes which have processes arranged in longitudinal bundles (bergman glia in the cerebellum)
- processes with end feet are often located on the surface of blood vessels where they for the key element of the BBB
astrocytes insulate blood vessels from the parenchyma side and control BBB
the extensions of astrocytes, called astrocytic end-feet, wrap around blood vessels, especially in the capillaries (neurovascular unit)
astrocytic end-feet influence the function of the endothelial cells in the blood vessels, contributing to the formation and maintenance of tight junctions that control the passage of molecules
barriers for diffusion of molecules via BBB:
- endothelium (2 membranes)
- basal lamina
- astrocyte end-feet (2 membranes)
what molecules can pass the BBB via diffusion?
only lipophilic molecules can pass BBB via diffusion
all other molecules need either carriers/transporters or specialised
channels
how does water move across the BBB?
via aquaporins
how does glucose move across the BBB?
assisstance of transporters from GLUT family
how does lactic acid move across the BBB?
lactate moves using
monocarboxylate transporters (MCT)
why do astrocytes no generate action potentials?
astrocytes do not generate action potentials but they have a very negative membrane potential
(usually below -80 mV) which can slowly change within a few millivolts
astrocytes cannot generate action potentials because they do not express any significant quantity of voltage gated
sodium channels
why are astrocytes strongly polarised?
astrocytes have many very active potassium
channels (kir type)
this is the reason why they are so strongly polarised but also why their membrane has very low electrical resistance
astrocytes and calcium excitability
since the membrane of astrocytes does not depolarise sufficiently, they cannot operate voltage-gated
calcium channels, which are the key mechanism for initiating fast vesicular exocytosis in neurones or endocrine cells.
astrocytes can, however, release Ca2+ from intracellular stores, particularly in response to stimulation of
G-protein-coupled receptors
the resulting Ca2+ increase can trigger vesicular exocytosis of transmitters
what do astrocytes often form?
gap junctions
- ions (especially k
+ ions) and also larger molecules (e.g. glutamate, D-serine, lactate, glucose) can pass through
gap junctions
- they can therefore spread though the “astrocytic syncytium” and be widely distributed across
large areas (thousands of micrometers)
- this helps to keep the extracellular concentration of k
+ stable and also
to deliver molecules such as lactate and glucose to the network of neurones
why is redistribution of potassium across wider areas important?
it helps prevent exessive local build up of potassium, depolarisation of neurons and generation of epileptic activity
what do astrocytes release?
gliotransmitters
examples of gliotransmitters
ATP
D-serine
glutamate
L-lactate
anandamide (endocannabinoid)
how do astrocytes release gliotransmitters?
- can be triggered by an increase in intracellular Ca2+, for example for release of ATP via exocytosis
- can be gradient-dependent via diffusion through connexin hemichannels or transporter activity, for example for lactate
ATP as a gliotransmitter
the main excitatory transmitters of astrocytes are purines, such as ATP (and
adenosine which is formed from ATP in the extracellular space)
ATP stimulates receptors on adjacent cells (neurones and glia) and raises
intracellular Ca2+
this leads to “Ca2+ waves“ propagating through the astrocytic
network
astrocytes recycle neuronal glutamate
- astrocytes take up glutamate released in the synapses
- in the astrocyte, glutamate is converted into glutamine which is then returned back to the neurones which can again re-convert it to glutamate, package it into vesicles and use it for synaptic transmission
- this is known as glutamate-glutamine
cycle that sustains glutamatergic neurotransmission
key neuro-anatomical features of astrocytes
- small soma and numerous processes but no dendrites or axons
- end feet insulate the outer wall of all BB vessels, they control access to the brain for many essential molecules
- connected by gap junctions and may form a synctium which ions and small molecules may be distributed between multiple cells
essential physiological characteristics of astrocytes
- astrocytes are not excitable (cannot generate action
potentials) but usually have very negative membrane potentials - astrocytes display “calcium excitability” – fairly rapid elevations (seconds) of intracellular calcium
- they release “glio-transmitters”, signalling molecules which affect neighbouring neurones and other astrocytes
key functions of astrocytes in mammalian brains
- they play an essential role in control of glutamate metabolism and removal from
the synaptic cleft, this has a major effect on excitatory transmission in the brain - they control access of energy (glucose and lactate) to neurones; this has direct impact on the activity of neurones when the consumption of energy dramatically increases
- astrocytes are not “passive” cells: they can actively participate in physiological processes by modulating adjacent neurones
processes modulated by astrocytes
- astrocytes on the ventral surface of the medulla are chemosensitive and
participate in responses to blood CO2 - astrocytes are highly mechano-sensitive, the slightest mechanical
disturbance of their membrane causes powerful release of ATP. they may be
participating in regulation of cerebral blood flow. - astrocytes in the hippocampus affect neuronal circuits involved in memory
formation, this could be via supply of energy (lactate) on demand
