Serum Uric Acid, Energy Metabolism, Sympathetic Activation, and Goal-Oriented Behavior or "Grant-Money-Getting" Behavior

This article [Hunter et al., 1990: (http://www.ncbi.nlm.nih.gov/pubmed/2345757)] is one that I cited in a previous posting (http://hardcorephysiologyfun.blogspot.com/2009/03/interactions-of-caffeine-with-purine.html), but I didn't have time to discuss some interesting research that Hunter et al. (1990) discuss and cite. There's old research showing positive associations of serum uric acid (UA) levels with goal-oriented behavior and, essentially, activity level in general, and there's also some more recent research looking at UA per se as being a supposedly-reliable mediator of hyperactivity or mania or whatever other conditions. What interests me is the reasons why UA might be associated with goal-oriented behavior. I remember that a professor I took a class from once mentioned research showing that higher serum UA levels were associated with more success in getting grant money (in successfully getting grants awarded, etc.). He was referring to old research, from the 1950's or 1960's, but I wonder if it doesn't have to do with brain activity in some generalized sense. There's a vast amount of research showing that electrical stimulation or glutamatergic stimulation or noradrenergic activity increases extracellular-fluid (ECF) adenosine and UA levels in the brain. It's a generalized response that may just have to do with an increase in the metabolic demands of neurons. I tend to think that the cerebral metabolic activity or noradrenergic activity might just be making people slightly more aggressive or driven and might be accompanied by increases in sympathetic outflow from the central nervous system, and that could account for the serum UA elevations. That type of process, however, would not mean that low serum UA levels could not also be associated with excessively-prolonged increases in noradrenergic activity and sympathetic activation. There could be a pathological activation that would eventually compromise beta-adrenergic sensitivity, such as in people with multiple sclerosis (in whom the serum UA levels tend to be very low). Astrocytic beta2-adrenoreceptor density and sensitivity has been reported to be very low in people with MS, and there's research associating prescriptions for asthma (specifically beta2-adrenoreceptor agonists) with lower incidences of MS. Obviously, taking beta-agonists would be potentially dangerous for people with MS, and one would want to discuss that type of thing with one's doctor. The association only was found when researchers looked at medical records across many years, also, although beta2-adrenoreceptor activation does tend to be anti-inflammatory and immunosuppressive. One could make the argument that robust increases and equally-robust decreases in noradrenergic activity in the brain, accompanied by augmentations in sympathetic outflow, would produce elevations in UA that would account for the associations of high serum UA with goal-oriented behavior. Poorly-regulated noradrenergic activity could conceivably lead to gradual, "functional sympathectomy-like" changes (reduced beta-adrenoreceptor sensitivity) that could produce decreases in serum UA, etc. This is very general and imprecise, but it's interesting to think about. Low serum UA is a generalized feature of a variety of intracranial disease states and is thought to be partially a result of poor osmoregulation in the brain, such that the sympathetic innervation of the kidneys changes. The decreases in functional, sympathetic innervation of the kidneys is thought to play more of a role in the etiology of cerebral salt wasting (CSW) than in the etiology of syndrome of inappropriate antidiuretic hormone secretion (SIADH). But there must be some more precise neurobiological changes that could account for the UA depletion that occurs in SIADH and CSW, and I'm not convinced that it only has to do with osmoregulatory failures per se or with changes in renal UA reabsorption. I think it might have to do with derangements in energy metabolism. Here's an interesting article that shows that the intramitochondrial UA levels are higher in rats with diabetes [Kristal et al., 1999: (http://www.ncbi.nlm.nih.gov/pubmed/10496973)]. But as the disease process and poor glycemic control in the rats' diabetes became more pronounced, the UA production normalized or decreased again. That's potentially really important for understanding why UA is low in people with MS, and it also casts serious doubt on the use of all of these association studies showing UA to be some kind of "independent" risk factor for (or variable independently-associated with) cardiovascular disease. One could claim to be able to control for insulin sensitivity in some association study, but that's unlikely to be possible. Energy metabolism, as related to insulin sensitivity, is far too complex to control for in an association study that looks at some blood tests from 20,000 people.