023 + 024 Glia

Question 1

what type of cell make up the majority of the brain?

Answer 1

glial cells

Question 2

what is the difference between neurons and glial cells?

Answer 2

• neurons can conduct action potentials
• glial cells cannot conduct action potentials

Question 3

what are the names of main types glial cells in the CNS(5)?

Answer 3

• astrocytes
• oligodendrocytes
• microglia
• ependymal cells
• NG2 cells

Question 4

what are the names of main glial cells in the PNS(4)?

Answer 4

• myelinating Schwann cells
• non-myelinating Schwann cells
• satellite cells
• enteric glia

Question 5

what were glial cells described as when they were first discovered?

Answer 5

’ glue ‘ of the CNS

Question 6

what is the most common glial cells in the brain?

Answer 6

astrocytes

Question 7

what is the function of astrocytes (5)?

Answer 7

• developmental role in migration of neurons and axon guidance
• homeostasis of neuronal microenvironment: ionic, metabolic, neurotransmitter uptake
• Blood-brain barrier induction and maintenance
• nutrition of growth factors
• synaptogenesis and synapse remodeling

Question 8

describe the structure of astrocytes

Answer 8

= star shaped highlt ramified glial cells
- attach to neuron body and axon and connect to ependymal cells to link to vasculature
- interact with synpases, nodes of Ranvier, blood vessels…

Question 9

give some examples of astrocyte subtypes

Answer 9

• protoplasmic astrocytes
• fibrous astrocytes
• radial glial cells
• Bergmann glia
• Muller glia

Question 10

what is the structure and function of protoplasmic astrocytes?

Answer 10

• biggest astrocyte population in grey matter
  -mainly found in hippocampus and cerebral cortex
• very highly ramified (can touch multiple synapses in 1 area)
• involved in neuromodulatory role

Question 11

what is the structure and function of fibrous astrocytes?

Answer 11

• organized along white matter tracts
• less ramified and smaller
• can contact nodes of Ranvier
• maintain homeostasis in their region

Question 12

what is the structure and function of radial glia cells?

Answer 12

• long thin cells stretching from apical to basal
• used in neuronal migration during cerebral cortex development
• known as the main neuronal/glial progenitor present during brain development

Question 13

what is the structure and function of Bergmann glia?

Answer 13

• specific astrocytes for cerebellum
• ensheaths and controls cerebellar synapses
• also involved in granular cell migration

Question 14

what is the structure and function of Muller glia?

Answer 14

• astrocyte type specific for retina
• involved in cell migration, neuronal generation and control of synapses of the retina

Question 15

describe the function of astrocytes and the neurovascular unit

Answer 15

• astrocytes have connections called ‘end feet’ which signal to blood vessels to expand or narrow the blood vessels to control flow of oxygen and nutrients
• astrocytes can release gliotransmitters (like glutamate) to send signals to neighboring neurons
• so this allows a sense of synaptic activity to control delivery of oxygen and nutrients

Question 16

what are pericytes?

Answer 16

• multifunctional cells embedded in the walls of capillaries in the CNS that connect to astrocytes
• important for blood vessel formation, maintenance of the blood-brain barrier, regulation of immune cell entry to the central nervous system (CNS) and control of brain blood flow

Question 17

what is the tripartite synapse?

Answer 17

• 3 part synapse
• pre-synaptic synapse
• postsynaptic synapse
• enwrapped by the astrocytic process
• allows astrocytes to modulate synaptic transmission by increasing or decreasing the amounts of ions or taking up/releasing more or less neurotransmitter like glutamate

Question 18

what are oligodendrocytes?

Answer 18

• type of glial cell
• myelinates neurons in the CNS = white matter

Question 19

describe the structure and function of myelination from oligodendrocytes

Answer 19

• myelin deposition is an active process
• oligodendrocytes wrap around axon in multiple layers
• different lengths and thickness of myelin on axon determines its function and speed of transmission
• it organizes the neuronal network and the types of information transfer
• allows for local communication between neurons and immune cells

Question 20

what is active myelination of the CNS?

Answer 20

• increasing the myelination/white matter of the brain
• increased when learning motor skills
• e.g. study showed increased white matter in forebrain after learning piano

Question 21

what cells myelinate the CNS?

Answer 21

oligodendrocytes

Question 22

what cells myelinate the PNS?

Answer 22

schwann cells

Question 23

what is a Remark bundle?

Answer 23

• Schwann cells bundle unmyelinated C-fibres together to form Remark bundles
• they provide protection and trophic support to unmyelinated axons
• upon injury, Schwann cells recruit macrophages to clear away damaged debris and then actively promote and support axonal regeneration through the synthesis and secretion of growth factors, extracellular matrix molecules and cell adhesion molecules

Question 24

what are NG2 cells?

Answer 24

• also called oligodendrocyte precursor cells (OPCs) or polydendrocytes
• exist throughout grey and white matter of the developing and mature CNS
• they transform into different kinds of glia such as oligodendrocytes and astrocytes, but also into neurons (replace injured cells)
• important in MS

Question 25

what are ependymal cells?

Answer 25

- create CSF and line ventricles of the brain and central canal of the spinal cord - the cells are cuboidal/columnar and have cilia/microvilli to circulate and absorb CSF - regulate osmotic pressure and ion homeostasis

Question 26

what are the functions of microglia (4)?

Answer 26

1. immune cells of CNS = surveillance of the surrounding tissue for infection, if detect then can become phagocytic to remove 2. important for brain development and homeostasis as they prune synapses (remove excess connections in fetus during development) via complement cascade 3. involved in neurodegenerative disorders and pain, can cause programmed cell death of neurons 4. involved in neuroplasticity (ability in nervous system to change in response to damage)

Question 27

what is microglia's immune function?

Answer 27

- surveillance of surrounding tissue in CNS for infection and injury - if detect, move towards damage and become phagocytic to remove

Question 28

what is microglia's function in development?

Answer 28

- synapse pruning - remove excess synapses and connections and strengthen important ones via complement cascade - in fetal and adult development

Question 29

what is a possible theory of microglia's role in autism spectrum disorder?

Answer 29

- problem in microglial complement cascade in pruning synapses - less synaptic pruning in early life (through C3?) - more abnormal connections/synapses left

Question 30

what is a possible theory of microglia's role in schizophrenia?

Answer 30

- mutation in MHC --> higher expression of C4a in complement - causes increased synaptic pruning - loss of grey matter and reduced synaptic density

Question 31

what is a possible theory of microglia's role in Alzheimer's disease?

Answer 31

- mutation in microglial genes - microglia usually attract to and clear away amyloid plaques and debris, but cannot with this mutation = distressed = release cytokines - this causes inflammation = synaptic loss and then cognitive decline in the CNS linked with Alzhiemer's disease

Question 32

what is microglia's role in neuropathic pain?

Answer 32

- peripheral nerve injury --> damaged primary afferent fibres express and release CSF1 in dorsal horn - spinal microglia excessing the CSF1R and adopt a reactive phenotype characterised by the upregulation of P2X4Rs - activation of these receptors stimulate BDNF which in the intercellular signalling molecule - BDNF activates neuronal TrkB, downregulating KCC2 resulting in neuronal disinhibition --> pain neurones hyper excitable