Session 2 - The Environment of the Brain Flashcards
What are the two main consitutients of the CNS?
Neruones and Glial cells
What are the two main roles of neurones?
Sense changes
Communicate with other neurones
Give the five roles of glial cells
Support
Nourish
Insulate neurones
Remove waste
What are the three main types of glial cell?
Astrocytes
Oligodendrocytes
Microglia
What are the four main roles of astrocytes?
Offer structural support
Help to provide nutrition for neurones
Help to remove neurotransmitters
Help to buffer K+ in brain ECF
Why is it necessary that astrocytes provide nutrition for neurones?
Neurones cannot store glycogen, and thus get most of their glucose from blood. This causes issues when they need a LARGER supply of energy
How do astrocytes provide nutrition for neurones?
Act as a store of glycogen
Produce lactate, which can be transferred to neurones to supplement their supply of glucose
How do astrocytes help to remove neurotransmitters?
Uptake spare neurotransmitters from synaptic cleft, removing them from functional circulation.
Why is it important astrocytes remove neurotransmitters?
- Helps to stop transmitter spilling over to neighbouring cells
- helps terminate the synaptic response
- Helps to recycle transmitters or breakdown product back to terminal
- Also keeps glutamate levels down, as too much is toxic to neurones
HOw is glutmate toxic to neurones?
Causes opening of NMDA receptors, leading to calcium entry - excessive glutamate causes excessive opening and excessive activation
How do astrocytes help to buffer K+ in the brain?
K+ ions move out of neurones during repolarisation after an action potential, an event which occurs a huge amount in the brain.
Astrocytes take up K+ via action of Na-K-ATPase
What is the role of oligodendrocytes?
Responsible for myelination of axons in the CNS
What do microglia do?
o The macrophages of the brain - immunocompetent cells, which recognise foreign material. When activated they phagocytose foreign material and debris.
o Can also act as an antigen presenting cell to T cells.
What is the blood brain barrier?
A theoretical dividing walls which exists to maintain the environment of the brain in a steady state, protecting it from extracelluar ion changes, peripheral hormones and drugs. Also prevents circulation neurotransmittes from entering CNS.
Outline the structure of th eblood brain barrier
o Endothelial cells of cerebral capillaries have very high resistance tight junctions between them
Even small ions cannot permeate between the cells
Also basement membrane of capillaries
o Astrocytes have foot processes that adhere to the capillary endothelial cells, so they are entirely enclosed.
Also secrete factors that help to maintain the endothelial cell tight junctions
What molecules can simply diffuse across the BBB?
Water and lipid soluble molecules can diffuse across
Sustances such as glucose, amino acids and potassium are transported across (conc can be controlled)
What is mean by stating that the CNS is immunopriveledged?
Less vulnerable to the vagaries of the immune system
Why does the CNS have to be immune privileged?
Rigid skull will not tolerate volume expansion, so too mcuh inflammatory response would be harmful
How do immune reactions occur in the CNS?
o Microglia act as antigen presenting cells to T cells, which can enter the CNS via post-capillary venules
o CNS inhibits the initiation of the pro-inflammatory T-cell response
Give four main structural features of a neurone
o Cell body (Soma)
o Dendrites
o Axon
o Terminals
Outline the course of neurotransmitter release
Opening of Voltage gated Ca2+ channels
The action potential arrives at the presynaptic membrane. This causes the opening of voltage-gated Ca2+ channels and the subsequent influx of calcium ions down their concentration gradient.
Formation of Snare Complex and Neurotransmitter Release
This increase in intracellular calcium concentration leads to Ca2+ binding to Synaptotagmin, leading to the formation of the Snare Complex and Ach release.
Give three different classes of CNS neurotransmitters
Amino acids
Biogenic amines
Peptides
Give an excitatory amino acid based neurotrasmitter
Glutamate
Give an inhibitory amino acid neurotransmitter
GABA (brain) and glycine (Brainstem and Spinal Cord)
Give three biogenic amines NTs
Acetylcholine, Noradrenaline, Dopamine, Serotonin (5-HT), Histamine
Give three pepitde NTs
Dynorphin, enkephalins, Substance P, somatostatin, Cholecystokinin, Neuropeptide Y
Give three glutamate receptors
o AMPA Receptor – Ion channel is Na+ and K+ permeable
o NMDA Receptor – Ion channel is Ca2+ permeable
o Kainate receptor
What makes up 70% of CNS synapses?
o Over 70% of CNS synapses
o Have both AMPA and NMDA receptors
o NMDA receptors need glutamate to bind and the cell to be depolarised to allow Ca2+ entry (and subsequent neurotransmitter release)
What is synaptic plasciticity?
Glutamate receptors are thought to have an important role in learning and memory
o Activation of NMDA receptors and mGluRs can lead to up regulation of AMPA
o Strong, high frequency stimulation can cause Long Term Potentiation (LTP)
This is thought to be the basis of long time synapse strengthening and learning
What is excitotoxicity?
o Ca2+ entry through NMDA receptors is important in Excitotoxicity.
o Too much Glutamate Excitotoxicity
o Astrocytes take up glutamate from the synaptic cleft to prevent this (see above)
What causes inhibition of GABA and glycine receptors?
have integral Cl- ion channels. The opening of these channels causes hyperpolarisation, decreasing action potential firing (inhibitory post-synaptic potential IPSP).
o GABAA is the main inhibitory neurotransmitter in the brain, and is bound by barbiturates, benzodiazepines. Both of these enhance channel response to GABA.
o Glycine is present in high concentrations in the spinal cord and brainstem
Name four biogenic amines
o Acetylcholine, Noradrenaline, Dopamine, Serotonin (5-HT)
What do biogenic amines do?
o Mostly act as neuromodulators
o Confined to specific pathways
Give three places in which acetylcholine is a neurotransmitter
o Neurotransmitter at neuromuscular junction, ganglion synapse in autonomic nervous system, postganglionic in parasympathetic nervous system
What does acetylcholine act on in the CNS?
o In CNS acts on both nicotinic and muscarinic receptors in the brain
Mainly excitatory
Receptors often on presynaptic terminals to enhance the release of other transmitters
Main functions are arousal, learning and memory and motor control
Where are the chlinergic pathways in the CNS located?
o Neurones originate in the basal forebrain and brainstem
o Diffuse projections to many parts of the cortex and hippocampus
o Also local cholinergic interneurons (e.g. corpus striatum)
What is the pathology of alzhermiers disease?
o Degeneration of cholinergic neurones in the nucleus basalis of Meynert is associated with Alzheimer’s disease
o Cholinesterase inhibitors are used to alleviate symptoms of Alzheimer’s disease
Give three pathways in brain involving dopamine
o Nigrostriatal Pathway
Motor control
o Mesocortical and Mesolimbic Pathways
Mood, arousal, reward
What is parkinson’s disease associated with?
The loss of dopaminergic neurones in the substantia nigra
How can parkinsons be treated?
With L-DOPA (converted to dopamine by DOPA decarboxylase)
What is a possible aeitology of schizopherenia? Back up with example
May be due to release of too much dopamine
- Amphetamines release dopamine and noradrenaline, which produces a schizophrnic like behaviour
What do anti-psychotic drugs target?
Dopa,mine D2 receptors
Where does noradrenaline in the brain come from?
Lcus ceruleus
When are locus ceruleus active (and not)?
Locus Ceruleus neurones inactive during sleep
Activity increases during behavioural arousal
- Amphetamines increase release of noradrenaline and dopamine and increase waefulness
What is the relationship between mood and state of arousal?
Depression may be associated with a deficiency of NA
What are the functions of serotnin?
o Functions include sleep/wakefulness, mood, vomiting centre in brainstem
What do SSRIs do?
o Selective Serotonin Reuptake Inhibitors (SSRIs) increase the concentration of serotonin in synapses, treating depression and anxiety
