Lecture 6 - Serotonergic System

Question 1

Serotonin

Answer 1

• Involved in all aspects of the body (sex, development, sperm morphology)
  
  • Systems compete for energy and respond in kind (immune system for instance)
  • anorexia, depression, anxiety, alzheimers
• 5-HT (hydroxytryptomine)
• 5-HIAA = 5 Hydroxyindoleacetic acid
• Contained in besicles at the synapse, bind with the membrane and release serotonin into the synapse
  
  • Some is returned (SERTS) and binds to on a receptor back on itself (feedback loop)
    
    • By MAO-A: monoamine oxidase
• 5% in the brain, 90% in the intestines
  
  • Cannot pass the blood brain barrier and is made in the brain locally
• Evolutionarily ancient (1.2 billion)
• bidirectional control over many systems
• Also inhbiitory/excitatory in the brain
• It’s an upper and a downer, an energy regulator.

Question 2

SERT

Answer 2

• Serotonin Transporter: found in platelette cells and is necessary for clotting
  
  • Also regulates the amount of serotonin in the blood straem
• SERT is in every part of the body/organ

Question 3

Sertonin process

Answer 3

• Synthesized from tryptophan
• Regulated by SERT
• Precursor to mealtonin
• Main metabolit = 5-HIAA
• 14 different receptors, 7 excitatory, 7 inhibitory
  *

Question 4

5-HT and mitochondrial function

Answer 4

• Promotes electron transport (ATP)
• Transport becomes more efficient and doesn’t release ROS
• Serotonin used in every major system of the body and serves a specialized function (having different functions for different systems)
  
  • Bidirectional influence of vascular system, appetite, blood flow to where we are damaged, immune response when infected
  • Ingestion and digestion: storing/releasing of glucose/fat
• Metabolism/Serotonin graph
  
  • 5-HT = serotonin, 5-HIAA serotonin uptaker
    
    • Lots of serotonin in spleen, lungs(lots of uptake too), and heart (medium amount)

Question 5

Dorsal Raphe Nucleus

(And serotonin process, chalk board stuff)

Answer 5

• DRN: Involved in serotonin and connects to everywhere in the brain
  
  • Long axons terminate in various cortical regions in the brain
  • Also SERT in the cell body and exerts negative feedback loop (homeostatic regulation)
• Serotonergic neurons do not form tight synapses and are spread out
• All SSRI’s block about 70-80% of your sertonin
• Serotonin is not taken up by post-synapse. It binds, then is release and taken back up by SERT

Question 6

Homestatic Regulation Factors

Answer 6

1. Neuronal Firing: increased/decreased as required
2. Serotonin 1A found on the soma
3. SERT: Anti depresssants block SERT and has to resort to other factors to restore homeostasis
4. Synthesis of serotonin increase or decrease as the situation requires

Question 7

Evolution of the serotnergic system

Answer 7

• Argued that the function is to help the brains homestasis and/or phenotypic plasticity
  
  • Locusts use sertonin to move from solitary to swarming phase
• Probably both, because it’s very ancient (requires oxygen and cant be at a time where we had mitochondria and could convert it)

Question 8

Mitochondria

Answer 8

• Can go through oxidative phosphorylation or glycolysis
• OP = 32/36 per glucose
  
  • Takes place in the cytosol and glucose turns to pyruvate, goes through krebs cycle and moves through electron transport for ATP production
  • Needs oxygen to carry the electron. Oxygen destabilizes at end of cycle and damages the cell. ROS
• Glycolysis = 2 ATP but way faster. Less efficient.
• MAO-A (metabolizes sertonin) found in mitochondria on outer membrane and 2 enzymes involved in synthesis of sertonin are IN the mitchorndria
  
  • Provides some evidence for this
  • Thought to have evolved from an alpha protobacteria and these enzymes exist in these. Gene transfer explains why 2 enyzmes are inside

Question 10

Spleen and Lungs explanation

Answer 10

• Spleen: Contains serotonin for clotting process, build up stores for t/b-cell function
  
  • Explains why it has so much and not many 5-HIAA
  • Can produce it’s own sertonin
  • 5-HT also necessary for the proliferation of T/B-cells
• Lungs: Lower metabolisim but obviously vulnerable to ROS
  
  • 5-HT is more important under low oxygen
  • Suggests higher serotonin uptake by the high 5-HIAA is to increase efficiency of ATP and reduce ROS
  • 5-Ht produced in the lungs
  • Fisher experiment

Question 11

Fisher Experiment

Answer 11

• Bathed lungs in 5HT in a bath of oxygen, nitrogen and a solution that reduces mitochondrial activity.
  
  • Only in the condition with the a reduced mitochondrial activity had less serotonin in it
  • The rate at which serotonin is taken up depended on mitochondrial acitivity

Question 12

Hypothalamus

Answer 12

• Responsible for how energy is allocated

Question 13

Smirga Mice Running Experiment

Answer 13

• Put mice on a running wheel for an hour, then made to run really fast or slow
  
  • Mouse at faster pace had a serotonin increase in the lateral hypothalmus (released serotonin) and slowly came down to baseline
    
    • Mirrors what happens with blood/glucose levels
    • Serotonin regulates energy of blood/glucose
• This regulation is controlled by serotonin for all kinds of things
  
  • Like sexual exhaustion (serotonin is highest at this point, and only when responsivity to sex returns is it coming down)