The Role of Neurones and Glia Flashcards
An important source of dopamine for the motor system can be found in which structure?
Substantia nigra
Which cell type can assume a macrophage-like appearance when activated?
Microglia
Which cell type is primarily responsible for maintenance of the BBB?
Astrocytes
What are the peripheral side effects of L-DOPA?
Tend to be GI related
- nausea
- anorexia
How are the side effects of L-DOPA ameliorated by giving carbidopa?
1) L-DOPA to dopamine by AADC (aromatic amino acid decarboxylase)
2) increased dopamine = GI side effects
3) carbidopa inhibits AADC = decreased side effects
What is the somatic nervous system?
Part of the peripheral NS
Responsible for voluntary muscle and reflex arc
What is the autonomic nervous system?
Parasympathetic and sympathetic NS
Controls bodily functions not consciously directed
What structures are in the peripheral NS?
Dorsal and ventral roots
Spinal nerves
Peripheral nerves
What structures are in the central NS?
Cerebral hemispheres
Brainstem and cerebellum
Spinal cord
Describe the blood supply of the brain
Anterior, middle and posterior cerebral arteries
Describe the cranial meninges
Dura mater - tough fibrous layer, adhered to bone (periosteal, meningeal)
Arachnoid layer - CSF present in subarachnoid space
Pia mater
What types of glia cells exist in the nervous system?
Astrocytes
Oligodendrocytes
Microglia
Astrocytes
Most abundant glial cell
Structural support
Provide nutrition for neurones = glucose-lactate shuttle
Remove excess neurotransmitters = important for glutamate as its toxic
Though K+ buffering = maintain ionic environment
Help form BBB
How do astrocytes provide energy for neurones?
Astrocytes supplements their supply of glucose
2 lactate is produced and transferred into the neurone
Lactate is then transformed into pyruvate
Why do astrocytes need to buffer K+?
High levels of neuronal activity = [K+] rise in brain ECF
Astrocytes take up the K+ to prevent this
Otherwise would change the pH and damage neurones
What cell type myelinate in the CNS vs the PNS?
CNS = oligodendrocytes
PNS = schwann cells
Outline the role of oligodendrocytes
Insulators
Responsible for myelinating the CNS
Describe microglia
Immunocompetent cells
Recognise foreign material = activated = change shape = phagocytose
Can act as APCs and present Ags to T cells that can enter the CNS
What is the role of the blood brain barrier?
Limits diffusion from blood to brain extracellular fluid = maintain environment for neurones
Formed by tight junctions between endothelial cells in the capillary, surrounded by astrocytes
What substances are transported across the BBB?
Glucose
AA
K+
What substances can get freely through the BBB?
H2O
O2
CO2
Hormones
How does the immune system in the CNS vary from the immune response in the rest of the body?
CNS inhibits initiation of pro-inflam T cell response = don’t want to much inflam in a bone box
Does not undergo rapid rejection of allographs
Outline the structure of a typical neurone
Cell soma
Dendrites
Axon
Terminals
Describe the neruotransmitter release
Depolarisation in terminal = opens voltage-gated Ca2+ channels = Ca2+ ions enter terminal
Vesicles fuse = release transmitter
Neurotransmitter diffuses across the synaptic cleft = binds to receptors on postsynaptic membrane
What types of receptors can be present on the postsynaptic membrane?
Ligand-gates
GPCR
What are the 3 main classes of neurotransmitters?
AA
Biogenic amines
Peptides
Describe AA neurotransmitters
Excitatory AA = glutamate
Inhib AA = GABA, glycine
How can glutamate receptors be classified?
Ionotropic = ion channels permeable to Na+/K+, activation causes depolarisation
Metabotropic = GPCR, changes in IP3 or inhib of adenylate cyclase
Explain glutamate receptors role in learning and memory
Activation of NMDA receptors (and mGluRs) can up-regulate AMPA receptors(initial fast depolarisation)
Strong, high frequency stimulation causes long term potentiation (LTP)
Ca2+ entry through NMDA receptors important for induction of LTP
Where are inhibitory AA neurotransmitters found?
GABA – brain
Glycine – brainstem and spinal cord
Explain how GABA and glycine receptors are inhibitory
GABA and glycine receptors have Cl channels
Open Cl = hyperpolarisation = inhibitory post-synaptic potential = decreased AP
What drugs enhance the response to GABA?
Barbiturates = anti-epileptic
Benzodiazepines = sedative, anxiolytic
What biogenic amines exist?
Acetylcholine
Dopamine
Noradrenaline
Serotonin (5-HT)
mostly act as neuromodulators
confined to specific pathways
What is the role of acetylcholine as a neurotransmitter?
neuromuscular junction
ganglion synapse in ANS
postganglionic parasympathetic
Outline the cholinergic pathways in the CNS
Pathway arising the the nucleus basalis (first to die in Alzheimer’s)
Projects throughout the cerebral cortex
Septal neurones projecting into the hippocampus (LTP)
Involved in arousal , learning & memory
Outline the dopaminergic pathways in the CNS
Substantia nigra (first to die in parkinsons) to striatum involved in motor control
Mesolimbic pathway to amygdala and hippocampus – control of mood, arousal, reward
What conditions are associated with dopamine dysfunction?
Parkinson’s = loss of dopaminergic neurones, treat: levadopa converted to dopamine
Schizophrenia = too much dopamine, treat: antagonists at dopamine D2 receptors
Outline noradrenaline as a neurotransmitter
transmitter at postganglionic – effector synapse in ANS
Also acts as a neurotransmitter in the CNS
Operates through G protein-coupled α- and β-adrenoceptors
Outline the noradrenergic pathways in the CNS
Locus coeruleus contain noradrengeneric neurones (pons/medulla)
Diffuse release of NA throughout
Outline how noradrenaline effects behavioural arousal
Locus ceruleus inactive during sleep
Activity increases during behavioural arousal
Depression associated with deficiency of NA
Where does noradrenaline come from?
NA comes from neurones in the locus ceruleus
Outline the serotonergic pathways in the CNS
Serotonin from the raphe nuclei to the rest of the brain
Function: sleep/wakefulness, mood
What can be used for the treatment of depression and anxiety disorders
SSRIs = selective serotonin reuptake inhibitors
