3 - Glia Flashcards
What is the most abundant glial cell and what are it’s roles?
Astrocytes
- Structural support
- Nutrition
- Remove neurotransmitters
- Buffer
- BBB
Glial cells are smaller than neurons but are greater in number than nerve cells in the brain. Glial cells do not have axon and dendrites. However, they come into play during neural development or recovery from neural injury and during modulation of synaptic action and propagation of nerve signals.
How do astrocytes provide nutrition to neurones?
Glucose-Lactate shuttle
Neurones cannot store or produce glycogen so astrocytes produce lactate from glucose for storage.
Lactate can be converted to to pyruvate when needed
How do astrocytes remove neurotransmitters?
- Removes glutamate from synapses to prevent excitotoxicity
- Too much glutamate is toxic to cells due to increased Ca causing increased excitability
How do astrocytes act as a buffer for the brain ECF?
- When neurones fire lots of A.Ps there is lots of K movement out of the cell
- Increase in K means neurones depolarise so inappropriate A.P firing so increased excitabilty
- Astrocytes have a slightly negative resting membrane potential so take up lots of potassium with chloride to stop this
What is the role of oligodendrocytes?
Myelinate and insulate the neurones in the CNS
Antibodies attack these in MS
What is the role of microglia?
Immunocompetent cells
- Become activated into phagocytes when they recognise foreign material
- Can antigen present to T cells
What components make the BBB?
- Tight junctions between capillary endothelial cells
- Basement membrane around capillary
- End feet of astrocyte processes
Only substances like water, CO2 and lipophilic substances can pass through easily
How do substances get across the BBB?
- Substances like glucose, AA and potassium are all through transporters to allow ECF to be controlled
Why is there a specialised immune response in the CNS?
- Normal inflammatory response would be harmful as skull prevents volume expansion
- T cells enter BBB and microglia antigen present to them.
- CNS inhibits the intiation of the proinflammatory T cell response
How are neurotransmitters released from neurones?
- Depolarisation in the terminal opens VOCC so Ca enters
- Calcium causes vesicles with neurotransmitters to fuse with presynaptic membrane and released into cleft to bind with post synaptic membrane
- Response depends on what receptor it is, e.g GPCR or nAchR
What are the different chemical classes of neurotransmitters?
- Amino acids
- Biogenic amines
- Peptides
Can be excitatory, inhibitory or modulatory
What are the main excitatory and inhibitory amino acid neurotransmitters?
Excitatory: glutamate
Inhibitory: GABA and Glycine
What are the different types of glutamate receptors?
- Metabotropic are GPCRs (same with GABA), these have a modulatory role
How does a fast excitatory response occur?
- Glutamate causes depolarisation of post synaptic cell by acting on LGIC and causing a EPSP
- AMPA LGIC causes initial fast depolarisation as they are linked to an Na/K channel to allow Na influx to depolarise
- When the cell has been depolarised NMDA LGIC are activated and they are linked to a Ca channel to allow Ca in, which is important for memory and learning
How are NMDA receptors activated?
- Cell needs to be depolarised to move Mg from pores and glutamate also needs to be bound
- Glycine can act as co-agonist
How are NMDA receptors involved in learning and memory?
- Low levels of glutamate activates AMPA receptors which depolarise the cell and activate NMDA receptors
- Movement of Ca through NMDA induced long term potentiation and upregulation of AMPA receptors so cells are more sensitive to glutamate
ncluding long-term potentiation and long-term depression, which are important cellular correlates for learning and memory function …
How is excitoxicity caused? How could dead cells cause this?
- Too much glutamate, lots of calcium uptake through NMDA so toxic
- e.g when patients have a stroke their glutamate levels can be toxic as dead cells release potassium which causes depolarisation and activation of NMDA so increasing Ca
The N-methyl-D-aspartate (NMDA) receptor is a receptor of glutamate, the primary excitatory neurotransmitter in the human brain.
How do GABA and glycine act as inhibitory neurotransmitters?
And where specifically?
- GABA mainly in brain, glycine mainly in brainstem and spinal cord
- Receptors have integral Cl- channels so causes hyperpolarisation and IPSP so decreased AP firing
How do barbiturates and benzodiazepines work as drugs?
What are they used to treat?
- Bind to GABA receptors to enhance the response to GABA to decrease neuronal activity
- Barbiturates: anti-epileptic drugs and previously sedative/anxiolytic. Risk of fatal OD and dependence
- Benzodiazepenes: treat anxiety, insomnia and epilepsy. have sedative and anxiolytic effect
What neurotransmitter is involved in reflexes? Example?
- Glycine at inhibitory interneurones
- e.g released on patella reflex to relax hamstrings
What are some neurotransmitters that act as neuromodulators?
Biogenic amines and Ach
Neuromodulators are substances that do not directly activate ion-channel receptors but that, acting together with neurotransmitters, enhance the excitatory or inhibitory responses of the receptors.
Where is most of the Ach in the CNS released?
- Nucelus Basalis releases Ach diffusely into the cortex and hippocampus
- Involved in arousal, memory and motor control
How is the nucleus basalis related to Alzheimer’s?
Where is it in the first place?
- First neurones to die in Alzheimers are here so lack of Ach release leading to memory loss and loss of motor control
- Cholinesterase inhibitors used to help symptoms of Alzheimers as they stop Ach breakdown
Located in basal forebrain
Where is most of the dopamine in the CNS released from?
How is Parkinson’s disease associated with dopamine dysfunction, and how can it be treated?
- Nigrostriatal pathway is the first to die so lack of dopamine to this area of the brain and lack of motor control
- Give levodopa, which is converted to dopamine by DOPA decarboxylase (AADC) in the brain. Give with carbidopa
How does Schizophrenia come about? And how do drugs solve this?
- Too much dopamine release
- Antipsychotic drugs are dopamine receptor antagonists
- Drugs like amphetamines can produce schizophreic like behaviour as they cause NA and dopamine release
What is the role of noradrenaline in the CNS?
- Outside the CNS it acts at postganglionic sympathetic synapses
- In CNS acts on GPCR alpha and beta receptors
- Release from locus cerelus in the brainstem and diffuses through cortex, hypothalamus and cerebellum. Modulates mood and arousal as LC not active in sleep
What is the function of serotonin (5-HT)?
- Helps with mood and sleep
- SSRIs can be used to treat depression and anxiety
(MAKE SURE YOU KNOW THE NUCLEI FOR ALL OF THE NEUROTRANSMITTERS PREVIOUSLY MENTIONED)
What is a peduncle?
White matter connecting a hemisphere to the brainstem
What is the cerebrum?
- Part of the forebrain
- Forebrain = cerebrum and thalamus
Label the different parts of the midbrain, including their roles. (Mickey Mouse)
- Ears: cerebral peduncles (descending motor fibres)
- Eyes: red nucleus (motor control, pigmented in life)
- Eyebrows: substantia niagra (dark in life)
- Tears: medial lemniscus (part of sensory system up to thalamus)
- Mouth: cerebral aqueduct surrounded by periaqueductal grey matter
- Triangle nose with tendrals: CNIII nucleus and EdingerWestphal with fibres of CNIII
- Double Chin: superior colliculus (reflext visual actions. inferior colliculus would be auditory reflex)
