As I have anticipated last week (have a look here to figure out some of the new therapeutic targets for migraine), the main character of my master thesis in Neurobiology is the kynurenic acid (KYNA), one of the neuroactive compounds produced during the metabolism of tryptophan, an amino acid used in the biosynthesis of proteins.
Indeed, tryptophan is the precursor for the synthesis of serotonin (have a look at this post to know what serotonin is and why it is defined the molecule of happiness) and it is one of the few privileged compounds that is transported across the blood-brain barrier (BBB) (a highly selective semipermeable border that separates the circulating blood from the brain and extracellular fluid in the central nervous system (CNS)). 95% of the tryptophan transported in the brain is metabolized in the kynurenic pathway, rather than the serotonin one, and, during its metabolism in the kynurenic pathway, the tryptophan produces several compounds, of whom the KYNA seems to be a very promising alternative for the treatment of some pathologies of the nervous system, one of them being migraine.
Evidences show how KYNA has antinociceptive effects on neurons in charge of transporting the pain signals (the administration of KYNA has basically has an antipain effect), probably through an inhibitory action on the brain areas responsible for generating migraine (see my previous post for a schematic of these sites). Unfortunately, KYNA does not cross easily the BBB, but researchers showed how one analogue (a compound having a structure similar to that of another compound, but differing from it in respect to a certain component) called KYNA-A1, is able to cross the BBB and seemed to be more effective than KYNA itself in its antimigraine effect.
To study the possible positive effects of KYNA-A1, the analogue of KYNA object of my study, we needed a good experimental model to verify its anti-migraine effects, both behaviourally and molecularly. To do so, we used an animal model of migraine based on the administration of nitroglycerin (NTG), a compound that not only releases nitric oxide (NO) but also induces the endogenous production via the activation of the nitric oxide synthase (NOS) (have a look at my previous post to figure out the role of NO in migraine). Moreover, the administration of NTG in the animal stimulates the activations of all the brain areas involved in migraine and the productions and release of all the compounds involved in this pathology, such as the CGRP.
Behaviourally, the animal response to the injection of NTG is associated with flinches or shakes of the injected paw or face rubbing, depending on the site of the NTG administration (typically one of the hind paws or one of the upper lips) that are then counted by the operator (see picture below for a schematic of the behaviour that we measured for my master thesis).
I later will present to you the paper that came out on Cephalalgia after I finished my master thesis with some of the data I produced in another post. Definitely it was a big deal for me finally having my name on a scientific paper and I will share it with you soon.