Week 2 - Drewes

Question 1

What are the main categories of neurotransmitters?

(List examples)

Answer 1

• Biogenic amines
  
  • Biogenic amines (Acetylcholine, Epi, NE, 5HT)
  • Amino Acids (GABA, glycine, glutamate)
  • Nucleotides/Nucleosides (adenosine/ATP)
  • Other (NO, CO)
• Neuropeptides
  
  • Opioid peptides (Neoendorphins)
  • Posterior pituitary peptides (Oxytocin)
  • Tachykinins (Neurokinin A/B)
  • Glucagon-related peptides (Glucagon)
  • Pancreatic polypeptide-related peptides (Neuropeptide Y)
  • Other (Somatostatin)

Question 2

What are the differences between a classical small molecule NT and a peptide NT?

Answer 2

• Small molecule NT
  
  • Synthesized in pre-synaptic terminal by enzymes made in the nucleus
• Peptide NT
  
  • Synthesized in nucleus and transported to pre-synaptic terminal

Question 3

What criteria is used for identifying a NT?

Answer 3

​1. Needs to be present at nerve terminal

2. Needs to be released
3. Must have a receptor to bind to
4. Response should be able to be blocked or activated

Question 4

What is the metabolic pathway for glutamate biosynthesis?

Answer 4

• Glutamate is released by neuron →
• then Inactivated by being taken up by astrocytes →
• converted to glutamine in astrocyte →
• transported back to the neuron for reuse

***Glutamate is not degraded

Question 5

Describe the metabolic and cellular pools of brain glutamate.

Answer 5

***

Question 6

What are the subtypes of glutamate receptors?

Answer 6

• Ligand gated ion channel (Na+) → fast
  
  • AMPA
  • NMDA
  • Kainate
• Metabotropic → uses 2nd messenger (GPCR), slow
  
  • Quisqualate B

Question 7

What are the key features of the NMDA receptor?

Answer 7

• both ligand-gated and voltage-dependent
• requires co-activation by two ligands: glutamate and either D-serine or glycine
• predominant molecular device for controlling synaptic plasticity and memory function

Question 8

How are glutamate receptors involved in ischemic cell damage?

Answer 8

***

Question 9

What is excitotoxicity?

Answer 9

• Excitotoxicity → when too much glutamate is released, it lets too much Na+ and Ca2+ enter cell →
  
  • Na+ influx water follows (osmosis) and cell dies!
  • Ca2+ influx causes mitochondrial damage and nuclear damage

Question 10

How is the NT glutamate inactivated?

Answer 10

Glutamate taken up by astroglial cells is converted to glutamine. Glutamine is inactive in the sense that it cannot activate glutamate receptors, and is released from the glial cells into to extracellular fluid. Nerve terminals take up glutamine and convert glutamine back to glutamate. This process is referred to as the glutamate-glutamine cycle, and is important because it allows glutamate to be inactivated by glial cells and transported back to neurons in an inactive (non-toxic) form.

Question 11

What role do glutamate receptors play in human disease?

Answer 11

***

Question 12

What neurodegenerative disorders involve glutamate receptor activation?

Answer 12

MS, ALS, Parkinson’s, Alzheimer’s

Question 13

What is Anandamide?

Answer 13

an endogenous cannabinoid neurotransmitter

Question 14

What is unique about Anandamide’s place of synthesis and its receptor?

Answer 14

• Anandamide → made and packed in postsynaptic then sent up to presynaptic to react on what is usually being released to cause release of NT
  
  • Retrograde transport → synthesized in postsynaptic and receptor is on presynaptic neuron

The presynaptic receptor is the same receptor that THC (Tetrahydrocannabinol) works on.