Tutorial 01 – Part 2 Flashcards
What does „sugar“ commonly refer to?
Sucrose, a disaccharide consisting of one glucose and one fructose molecule
Where is the intramolecular bond cleaved in?
The gut
Via which pathways are glucose and fructose absorbed?
Via different metabolic pathways
Sugar vs fructose (caloric value and physiological responses)
Sugar generally signals high caloric value and the physiological responses are generally much stronger to glucose than to fructose
What is the only nutrient neurons/the brain can use for energy production?
Glucose
How is sugar conditioning possible?
Even without tasting the sweetness (e.g. in direct intestinal infusion via gastric tube)
Where are the cells necessary and sufficient for sugar conditioning found?
In the proximal small intestine (duodenum, jejunum)
What is a cell type with neuron-like behavior in the mucosal lining of gut called?
Neuropod cells
Where can neuropod cells be found?
In the mucolsal lining of gut
What happens when neuropod cells bind to sodium-glucose co-transporter channels
Influx of sodium
What happens after the influx of sodium (neuropod cells)?
Taste-receptor like receptors start second-messenger cascade with release of Ca2+ from intracellular storages, which opens a second set of Na+ channels
What happens after the second set of Na+ channels are opened (neuropod)?
KATP-channels close on intracellular binding of ATP increase (after intracellular glucose metabolization)
What do the three processes (influx of sodium, Na+ channels are open, KATP channels close on intracellular binding of ATP-increase) cause in neuropod cells?
Depolarization
How are the extensions of neuropod cells and where do they go to (also what potentials does it cause)?
Axon-like extensions harbor vesicles with glutamate, which is released onto dendrites of the vagal nerve and cause excitatory post-synaptic potentials
Where does the vagus nerve forward the signal to (neuropod)?
To the nucleus tractus solitarius (NTS) in the medulla
What is taste receptor called (neuropod)?
T1R3
What happens from T1R3 on?
- second messenger cascade
- Ca2+ release
Na+ influx via TRPM5 channels
What is the sodium-glucose co-transporter called and what does it do?
SGLT1: direct Na+ influx
What closes upon ATP binding
KATP channels
What are voltage-gated calcium channels doing?
VGCC amplify process and induce hormone release
What are KATP channels doing?
Closes upon ATP binding
What is responsible for direct Na+ influx?
SGLT1 (sodium-glucose co-transporter)
Where does nucleus tractus solitarius receive input from?
Gut, but also oral cavity (sensation of sweetness and intestinal sugar signaling), as well as olfactory and visual cues (motivational)
Where does the NTS (nucleus tractus solitarius) project to?
To the hypothalamus, central nucleus of amygdala, locus coeruleus (release of noradrenaline increases arousal), dorsal raphe (serotonin increases motivation and mood), SNc and VTA
In which pathways does sugar intake increase activity?
In Mesolimbic and Nigrostriatal pathways
Which pathway shows activity in sham-fed rats and which pathway does not (taste of sweetness, but no glucose intake)?
Mesolimbic activity increase but not nigrostriatal
Which side of the vagus nerve causes increase in which activity?
Left vagus nerve shows increase in mesolimbic activity, right vagus nerve increases nigrostriatal activity
How is the Nigrostriatal dopamine?
Post-ingestive only
How is the mesolimbic dopamine?
Pre-ingestive and post-ingestive
What can the midbrain dopaminergic system be divided into?
Substantia nigra pars compacta (SNc) and ventral tegmental area (VTA)
But separation is not strict with overlap and dopaminergic cells extending beyond boundaries
Which pathways is the midbrain dopaminergic system origin of?
Nigrostriatal ( ventral SNc, important for locomotion), mesolimbic and mesocortical pathway (dorsal SNc and VTA, important for reward signaling
By what is sugar perceived in the body?
Sugar is perceived by taste receptors in the mouth, but also by epithelial cells in the intestine that have neuron-like properties, e.g. the capacity to depolarize and release neurotransmitters onto dendrites of the vagus nerve
Signals of sugar are conveyed to which part of the brain?
The nucleus tractus solitarius of the medulla and forwarded onto reward circuitry in midbrain, but also hypothalamus and amygdala
Nigrostriatal dopamine pathway
Hepatic portal vain -> left vagus -> cNTS
Intestine -> right vagus -> cNTS -> PBN -> SNOc ->dorsal str -> cortex
Mesolimbic dopamine pathway
1) hepatic portal vain -> left vagus -> cNTS
Intestine -> right vagus -> cNTS -> VTA -> ventral str -> cortex
2) tongue -> cranial nerves 7, 9, 10 ->rNTS -> VTA -> ventral str -> cortex
Hoe does sugar travel trougj the body (simple)?
Gustation ( taste receptor cells) -> vagus nerve shows increase-> gut sense (neuropod cells)
