Since choosing a chalk talk to write about was so hard (everyone’s projects are so cool), I decided to go with the topic I found most intellectually intriguing. Martin Acosta’s presentation on ‘Rapid Tryptophan Depletion: Sex-mediated Differences in Rats’ stuck with me because of the parallels between our projects.
Tryptophan is an important amino acid which we obtain through our diets and which is metabolized into serotonin (an important neurotransmitter) in the brain after passing through the blood-brain barrier (BBB). Martin’s project offers an alternative to the social defeat (SD) paradigm to induce depression in rodents since SD is not effective in females and hence cannot be used to study sex-differences in depression. In their protocol, the Kuhn lab feeds rats a mixture of several large neutral amino acids (LNAAs) or a mixture of LNAAs & tryptophan. LNAAs compete with tryptophan molecules to pass through the transport proteins in the BBB. Therefore, rats fed only LNAAs have a higher proportion of them which prevent tryptophan from passing into the brain and being converted into serotonin (serotonin deficiency is associated with depression).
Although preliminary results from Martin’s study (which measures the levels of various metabolites in the rats’ blood and brains) have shown no differences in how male and female rats are affected, this is not the aspect interests me. Tryptophan plays an important role in the gut-brain axis—some bacteria are known to use up tryptophan leaving less to be metabolized by our bodies, while others produce it. Additionally, the kynurenine pathway is another important pathway for tryptophan metabolism. Kynurenine is produced from tryptophan and can be further metabolized in two ways with opposite effects—the end product of one pathway is neuroprotective while the other is neurotoxic. Altogether, tryptophan and its metabolites seem to play an important role in depression and are an important signaling pathway between the gut and brain. This is where my project comes in: I can’t wait to see the bacterial DNA sequencing results from the feces of the SD mice in my project to determine whether the bacterial species which are more/less abundant are implicated in the tryptophan pathway.
P.S. Tryptophan is one of my new favorite sounding words—try saying it, it’s addicting!