Rat brain symptoms and conditions

I have stated many times that I am not an expert. I just post what I find. This has been a mind boggling journey for me. This is way over my head but I struggle to read and understand. Finding answers to why children are suffering from neuro-psychiatric side effects is worth the effort.

I have made the following observations.

1. Some quinoline are known to be able to cross the blood brain barrier.
2. Molecules that ionize are known to be more likely to be able to cross cell membranes. So if montelukast ionizes as a result of change in blood pH to sufficient acid conditions that it ionizes, then it could be possible or maybe like that it does in fact cross the blood brain barrier.
3. We know that there are cysLT1 receptors in the brain.
4. We know that researchers believe that montelukast may bind at the arginine of the cysLT1 receptor.
5. We know that arginine contains four nitrogens. And montelukast contains one.
6. We don't know what happens to those nitrogens.
7. We do know what macrophages create nitric oxide as I posted.
8. We do know that if something cause excessive nitric oxide to build in the brain that there would be damage to the neurons.

Some people may remember when I got stuck at the astrocytes, the cysLT1 receptors and glutamate. I keep looking for research reports that may shed more light on this.

Titre du document / Document title
Nitric oxide causes glutamate release from brain synaptosomes
Auteur(s) / Author(s)
MCNAUGHT K. S. P. (1) ; BROWN G. C. (1) ;
Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)
(1) Department of Biochemistry, University of Cambridge, Cambridge, ROYAUME-UNI
Résumé / Abstract
We determined the ability of pathological levels of nitric oxide (NO) to cause glutamate release from isolated rat brain nerve terminals using a fluorometric assay. It was found that NO (0.7 and 2 μM) produced (4 and 10 nmol/mg of synaptosomal protein) Ca2+-independent glutamate release from synaptosomes (after 1 min of exposure). Spermine/NO complex (spermine NONOate; a slow NO donor) and potassium cyanide (an inhibitor of cytochrome oxidase) also caused Ca2+-independent glutamate release. Preincubation of synaptosomes with 5 μM 1H- oxadiazole quinoxalin-1-one (an inhibitor of soluble guanylyl cyclase) had no effect on NO-induced Ca2+-independent glutamate release. Ca2+-independent glutamate release produced by NO was greater in a low-oxygen medium. NO, spermine NONOate, and potassium cyanide inhibited synaptosomal respiration with a similar order of potency with respect to their ability to cause glutamate release. Because NO has been shown previously to inhibit reversibly cytochrome oxidase in competition with oxygen, our findings in this study suggest that NO (and cyanide) causes glutamate release following inhibition of mitochondrial respiration at the level of cytochrome oxidase. Thus, elevated NO production leading to mitochondrial dysfunction, glutamate release, and excitotoxicty may contribute to neuronal death in neurological diseases.
Revue / Journal Title
Journal of neurochemistry ISSN 0022-3042 CODEN JONRA9
Source / Source
1998, vol. 70, no4, pp. 1541-1546 (29 ref.)

INIST-CNRS, Cote INIST : 4037, 35400007527188.0230

Neurological problems and the effects of Singulair should be investigated. The Chinese researchers demonstrated that the CysLT1 receptor (singulair inhibits this receptor) does exist in the human brain. In the rat brain, they demonstrated that there is a link between this receptor and the astrocyte.

There are many researchers/doctors interested in excitotoxicity and damage to neurons.

http://www.jpands.org/vol9no2/blaylock.pdf

I would like to know how Singulair affects the astrocyte numbers and function. I would also like to know if there is a link between metabolism and the cysLT1 receptors in gastro-intestinal mucosa. Does Singulair affect the metabolic process?

So many parents are complaining of ADD/ADHD symptoms? The paper that I gave you the link correlates the immune response and excitotoxicity. That is very interesting. How many asthma and allergy patients also suffer from potential excitotoxicity? Does Singulair cause it in some patients or just make it worse in some patients? None the less--there is a possible link.

Is there a potential explanation for the adverse psychiatric side effects of montelukast?

In my opinion, there are at least some very good clues based upon the work of the Chinese researchers.

A 2006 report indicated that they had localized (meaning found it was there) the CystLT1 receptor (same as the receptor that montelukast
Singulair blocks) in the neurons of the brain tissue of rats. In order to do that, they injected rat brain's with NMDA to cause a chemically induced state of excitotoxicity. Excitotoxicity is a common factor in Central Nervous System disease. They concluded that both 5-LOX and CystLT1 were upregulated by the excitotoxicity that they artificially created
with the NMDA. Therefore, there would be a potential link between neuron activity and CystLT1. Nerve cells are damaged by excitotoxicity. These researchers used NMDA to cause nerve damage which caused the CystLT1 to show up. NMDA was often used in human behavior studies to cause brain damage. They would then try to observe whether behavior was compromised to conclude what areas of the brain determined what behavioral response.

So I was thinking about the Chinese researchers as I was reading other posts. One post interested me particularly regarding the mother who described behavior that seemed like hypoglycemics when their snack doesn't arrive on time. So a light bulb went on. Glutamate, another excitotoxin, can build up in the brain to a level that is damaging if humans become excessively hypoglycemic. If glutamate concentration around the synaptic cleft reaches too high a level then neurons die. Clinically, it really does seem that many people experience things that sound like the effects of hypoglycemia. It could be only a coincidence. But then again, maybe not.

The Chinese researchers found the CystLT1 receptor in the rat brain neuron after brain damage. They found the CystLT1 receptor in the normal human brain in the microvascular endothelial cells and in neuron and glial-appearing cells in brain trauma or tumors.

What role does the CystLT1 play in brain function? If it exists in brain tissue, we can assume that it does have a function. If it plays a role in preventing or repairing neuron damage due to excitotoxins, then there would be a very direct link between Singulair and adverse psychiatric side effects.

http://www.chinaphar.com/1671-4083/27/1526.htm

The bottom line is that Merck owes people who take Singulair further research regarding it's effect on the brain.