Intro to Neuropharmacology Flashcards
What are macroglia vs microglia? What are they derived from?
Macroglia - oligodendrocytes / Schwann cells, and astrocytes - derived from neuroectoderm
Microglia - macrophage-like cells - derived from myeloid lineage
What is one major function of glial cells as it relates to neuropathic pain?
Induction of central sensitization via chemokine interactions
-> glial cells like astrocytes are not just structural!
Why do inhibitors of mitosis (i.e. cancer chemotherapy) interfere with learning and memory?
Newly formed neurons from neural stem cells located in the dentate gyrus are responsible for learning. They are then taught the “rules of the road” from existing neurons.
What class of drugs has been shown to increase neuron production?
Antidepressants
What is the primary site of integration of synaptic inputs, and what type of channels do they contain?
Dendritic spines
Typically contain ligand-gated ion or metabotropic channels. Remember, there are NO voltage-gated sodium channels until the axon hillock
How are dendrites related to learning and memory?
Changes in the dendritic shape and architecture occur in response to synaptic activity. Connections that are used tend to grow, dendritic spines that do not make contact with active nerve terminal contract
Is potassium high on the inside or the outside?
High on the inside -> channels open to leak outward to hyperpolarize (positive charge leaving the cell causes relative negative charge inside)
What is anterograde axonal transport used for?
Shipping of organelles such as mitochondria, secretory vesicles, soluble and membrane proteins required for neurotransmitted synthesis and axon / nerve terminal maintenance
These are synthesized in the cell body
What is the primary usage of retrograde axonal transport? Why is this clinically relevant?
Transportation of neurotrophic factors, which are synthesized by the target cell, back to the cell body to provide the information needed for the neuron to continue surviving
Process of Wallerian degradation starts upon cutting off supply of neurotrophic factors
Where does classical neurotransmitter synthesis occur?
In the axon terminal. This is why there are many mitochondria around, for generating energy
What are the three major types of synapses, and do they tend to be excitatory or inhibitory?
- Axodendritic - excitatory
- Axosomatic - excitatory
- Axoaxonic - inhibitory -> hyperpolarizing
What happens when an action potential reaches a nerve terminal?
- Voltage-gated calcium channels open, allowing Calcium influx
- Calcium causes synaptic vesicles containing neurotransmitter to fuse with presynaptic membrane
- Released neurotransmitter diffuses across synaptic cleft and binds to receptors on postsynaptic membrane (ionotropic or metabotropic)
What is metabotropic called “indirect gating”
metabotropic processes are very slow -> utilize second messengers, and ultimately still lead to the activation of a channel.
I.e. Gs pathway leads to activation of protein kinase A, which phosphorylates a channel on the membrane to make it more active
What are the primary amino acid neurotransmitters? Excitatory or inhibitory?
- Glutamate - excitatory
- GABA - from decarboxylation of glutamate - inhibitory
- Glycine - inhibitory
What are the biogenic amines and their functional groups?
- Dopamine
- Norepinephrine
- Epinephrine
(all three made from tyrosine, have catechol group) - histamine - imidazole - from histidine
- serotonin - indole - from tryptophan
Why is nitric oxide considered an atypical neurotransmitter?
It is made on demand and released by diffusion, rather than being stored and released in vesicles
What are some examples of peptide neurotransmitters?
Opioids - enkephalin, dynorphin, POMC
Tachykinin - Substance P and Substance K
How are peptide neurotransmitters made and transported?
Made as large peptides which are cleaved from precursors to the active neurotransmitter via proteases
Transported to axon terminal from the cell boxy via anterograde transport (not made in nerve terminals)
Why is the transport mechanism of peptide hormones relevant?
Since they need to be transported, sustained stimulation of these nerves can lead to depletion of peptide neurotransmitter stores
How is inhibition of phosphodiesterase relevant as a druggable target?
Can prevent signal terminal via blocking cAMP breakdown, which is needed for metabotropic action
How can transporters be drugged?
Channels are needed to bring some neurotransmitters back into the neuron from the synaptic cleft (i.e. serotonin)
What is the function of endogenous cannabinoids?
Retrograde neurotransmitters -> transcellular signalling from the postsynaptic neuron to the presynaptic neuron, decreasing the excitability.
This is why these can be used to decrease pain and cause relaxation
How does direct beta-gamma G-protein gating work?
Ach binds the Type 2 muscarinic receptor, and beta-gamma subunit activates the G-protein gated K+ channel (GIRK)
What produces the slow EPSP via acetylcholine and what is the mechanism?
Muscarinic Ach receptor activation -> stimulates PLC to hydrolyze PIP2 to IP3 and DAG
Decrease in PIP2 causes the closure of M-type delayed rectifier K+ channel -> depolarizes the neuron
Where are dopaminergic neurons found?
Ventral tegmental area -> substantia nigra
They project to striatum in the basal ganglia (include caudate and putamen), and function in movement and brain reward pathways
What are the main cholinergic areas of the brain?
- Nucleus basalis - degrades in Alzheimer’s
- Pedunculopontine nucleus - motor control, reticular activating system
- Medial septal nuclei - emotions and sensations
What is the major norepinephrine releasing group of neurons in the CNS and what is their function?
Locus ceruleus - function in reticular activating system
Where are serotonergic neurons located in the CNS and what is their role?
Raphe nuclei
Project to diencephalon, basal ganglia, and basal forebrain among others.
Involved in modulating affect (mood) and pain, as well as excitability
