Glial Cell Biology Flashcards
Glial cell General Characteristics
– non-neuronal brain cells; 10-50x more abundant in the brain than neurons
o Majority of CNS cells
o Fraction of glia cells is proportional to the size of the animal (fruit fly has less than humans)
o DON’T directly propagate action potentials
o Do not retain ability to divide
o Derived from mesoderm or neuroectoderm
o 5 Types in CNS – astrocytes, oligodendrocytes, microglia, NG2 cells, ependymal cells
o 2 Types in PNS – satellite cells, Schwann cells
Astrocyte Characteristics
o “star-shaped”; most abundant and largest glial cell (20-50% of brain volume)
o Present in both gray and white matter
o Highly branched single astrocyte can contact 100,000 synapses
o Processes can contact neuronal cell bodies, dendrites, and axonal surfaces; blood vessels and capillaries
Varicose projection astrocytes – found in human and primate brains but NOT rodents
• Contain a lot of mitochondria indicating that they require a lot of energy and have function beyond interconnecting matrix
Varicose projections – “bumps/beads” along astrocytes
Astrocyte Derivation
o Derived from radial glial cells
Radial glial cell processes retract during CNS maturation and become progenitors of adult astrocytes
Bergmann glial (adult cerebellum) and Muller cells (adult retina) are radial glial cells remaining in adult brain
Astrocyte Structural Organization
Bidirectional communication with neurons through contact and chemical transmission
Form tripartite synapse – presynaptic neuronal element, postsynaptic neuronal element, and astrocyte
Gliotransmitters (glutamate, D-serine, ATP, TNFalpha) are released from astrocytes
o NOT all astrocytes are the same (depends on environment in portion of the brain)
Regional Heterogeneity exists but not understood
• Example: brain tumors occur in temporal lobe – something specific about the cells in this area makes it susceptible to tumor formation
Glial Fibrillary Acidic Protein (GFAP)
– intermediate filament that differentiates astrocytes from other CNS cells
• Protoplasmic – thick, short, and highly branches processes
o Found in gray matter; associated with neurons
o End in expansions called “end-feet” that form glia limitans (glia-limiting membrane)
Wrap around blood vessels and capillaries and release vasoactive substances that control blood flow
Surround epithelial cells of BBB – serve as “passageways” for the transfer of nutrients from the blood to neurons
Surround neuronal cell bodies, dendrites, and some axons
• Fibrous – thin, long, smooth, and less branched processes
o Found in white matter between nerve fibers; associated with axons
• Muller cells – unique to the retina
Astrocyte Function
o Neuronal migration and guidance – radial glia cells assist in migrating neurons during development
o Produce and secrete growth factors – regulate morphology, proliferation, differentiation, and survival of neurons
o Major source of extracellular matrix proteins and adhesion molecules
o Act as physical barrier (Protoplasmic astrocytes)
o Response to injury: Reactive Astrogliosis (fibrous astrocytes)
o Maintain brain homeostasis
o Formation and Modulation of Synapse
Astrocytes as Physical Barrier
End feet and Glial limitans
• Glia-limiting membrane (glia limitans) is a thick layer of joined end-feet at the surface of the brain covered by an outer basal lamina making contact with pia mater
o Passageways for the transfer of nutrients from blood to neurons
• End feet wrap around blood vessels and capillaries releasing vasoactive substances that control local blood flow
• Perivascular lining membrane - surrounds endothelial cells of blood brain barrier
o Also surround neuronal cell bodies, dendrites, and some axons
Astrocytes Response to Injury
Perform a defensive brain reaction by complex astrocyte remodeling
• Isolate damaged area by a local response to fill space left by lesion and a distal response to facilitate neuronal remodeling
Source of innate inflammatory mediators (microglia also perform this function)
• Astrocyte-microglia communication is key for innate immune respone
Astrocytes Maintaining Brain Homeostasis
Control blood flow by signaling blood vessels about need for oxygen and glucose
Buffer extracellular space by rapidly removing neurotransmitters and ions from the synaptic cleft after neurotransmission
• Provide energy and substrates for neurotransmission
• Ex: Glutamate-Glutamine Cycle
Astrocytes and Formation/Modulation of Synapse
Astrocytes release TNFalpha for “synaptic scaling”- form of neuronal plasticity
Bidirectional communication with neurons
Release chemical messengers
Astrocyte Clinical Diseases
o Glial scar – forms during spinal cord injuries
o Amyotrophic Lateral Sclerosis (ALS; Lou Gehrig’s Disease) – astrocyte release toxic factors that kill motor neurons
o Gliomas – astrocyte tumors (most common type of glial cancer)
o Tuberous Sclerosis & Epilepsy – from GFAP and astrocyte in tubers with impairment of astrocyte buffering of glutamate and potassium
Oligodendrocyte Structure and Function
o Smaller than astrocytes and only few branches
o Found in both gray and white matter
o 2 types
Interfascicular oligodendrocytes – in white matter
• Myelinate axons-1 oligodendrocyte can construct/maintain several myelin sheaths
Perinueral oligodendrocytes – in gray matter
• Lie next to neurons; unknown function
Oligodendrocyte Clinical Diseases
o Multiple Sclerosis (MS) – inflammatory demyelinating disease with oligodendrocytes and myelin sheath degeneration autoimmunity plays a role
o Progressive Multifocal Leukoencephalopathy (PML) – degeneration of oligodendrocytes and myelin sheaths
o Changes in myelination associated with cerebral infarcts, infections, premature infants with hypoxia/ischemia, leukodystrophies
o Clinical Depression – loss of oligodendrocytes and myelin
o Oligodendrogliomas (tumors) – usually slow growing and arise from perineural oligodendrocytes
Microglia Structure
o Smallest glial cells scattered throughout CNS
o Second most abundant glial cell (make up 20% of total brain glia); in both gray and white matter
o Derived from hematopoietic cells of monocyte-macrophage lineage (mesoderm) and yolk-sac-derived myeloid cells
o Few short branching processes with thorn-like endings
o Resting microglia – small rod-shaped with symmetrical processes; ramified processed
o Active microglia – thicker processes and larger, rounder cell bodies; can form more ameboid shape for easy movement
Microglia Function
o Resident immune cells of the brain – hallmark is their ability to become quickly activated and respond to pathological changes
o Survey the brain for damage and infection – once activated they phagocytose debris
o Mediate CNS inflammatory response – produce and secrete cytokines/chemokines and proinflammatory molecules (TNFalpha; IL1b; nitric oxide)
o Important during CNS development – phagocytose degenerating cells during normal developmental programmed cell death
o Synaptic Health – “Quad-partite Synapse” – may be involved in strengthening of synapse
Microglia Clinical Disease
o Stroke – leads to secondary cell death and some of the molecules secreted by activated microglia are neurotoxic (TNFalpha, IL1b)
o Bacterial Meningitis – blood brain barrier opened by excessive TNFalpha and IL1b which worsens infection as leukocytes infiltrate
o HIV – microglia are targeted by the virus, causes proinflammation
o Neurodegenerative disease – increased microglial activation
o Others: MS, autism, environmental toxins
Satellite Cell Structure and Function
o Surround cell bodies of sensory and autonomic ganglia
o Regulate the external environment; respond to ATP
o Connected by gap junctions
o Respond to injury and produce proinflammatory molecules
Schwann Cells Structure and Function
o Derived from the neural crest
o Provide myelin sheaths around peripheral axons; surround some unmyelinated axons too
o Other Roles: Developmental and Regenerative Role
Phagocytose damaged axons
Guide regeneration by forming a “tunnel” toward the target neuron
Produce neurotrophins
Needed for preservation of healthy axons
Schwann Cells Clinical Diseases
o Guillain-Barre syndrome – acute inflammatory demyelinating polyneuropathy where inflammation results in conduction block and muscle paralysis
Unknown etiology; ½ cases are triggered by acute infection
Autoimmune disease that destroys Schwann cells
Progresses from lower limbs upwards
o Chronic inflammatory demyelinating polyneuropathy
o Tumors – Schwannoma are encapsulated and easily removed
o Charcot-Marie-Tooth disease – NONfatal autosomal dominant demyelinating peripheral neuropathy causing weakness of foot and lower leg muscles (foot drop)
Most common inherited neurological disorder
Adolescent onset with varying severity
Distinguishing between CNS and PNS Myelination
CNS – white matter – made by interfascicular oligodendrocytes
Produce flattened process of plasma membrane that wrap tightly around the axon repeatedly; cytoplasm is removed as layers accumulate mature myelin sheath
Single oligodendrocyte can construct and maintain several myelin sheaths
PNS – made by Schwann cells
Wrap around axon and cytoplasm is excluded as the inner layers fuse; forms around peripheral axons; slightly more cytoplasm than in oligodendrocytes
1 schwann cell = 1 internode/axon
Myelination
o Myelin sheaths – electrochemically-insulating sheaths that conduct action potential quicker
Good insulators due to high lipid-protein ratio (80:20)
o Internodes – myelinated sections of axons
o Nodes of Ranvier – unmyelinated section of axon following each internode
o Salutatory conduction – process by which actin potential leap from node to node; facilitated by low resistance and high presence of sodium channels in Nodes of Ranvier
