Sunday, July 5, 2009

The sickness of not knowing, part 4

E. Ron de Kloet and co authors have reviewed and summarized the biochemistry of stress in a Nature Reviews Neuroscience, 2005. doi: 10.1038/nrn1683

The paper doesn't seem to be available for free on the internet. What this paper describes is the process involving hormones, genes and organs that gets triggered in response to stress. Sapolsky and co authors have reviewed the role of glucocorticoids in stress response. [doi: 0163-769X/00/$03.00/0]

Here's my understanding of whats happening.
Homeostasis is the technical term describing the equilibrium I was talking about earlier, in the scale of a cell. It is regulated by the pituitary gland in the brain. Vasopressin, oxytocin and a whole bunch of other hormones are stored in the pituitary gland and are involved in this homeostasis process. Out of these, oxytocin controls the negative effects of cortisol on the hypothalamus; estrogen amplifies its effect in women while male hormones kill the effects of oxytocin. So, just to clarify, the adrenal glands on the kidneys secrete adrenaline and glucocorticoid(GC) hormones, mainly cortisol; adrenalin combats mild stress response but severe stress is countered by GC ( in a very simplistic description of the biochemical process); both or only GC damages the hypothalamus cells. The interesting feature is that, these renal glands secrete something that works in the brain, yet the glands sit on the kidneys! By the way, the typical manifestation of GC activity on your brain is when you start shaking/trembling....you are basically killing hypothalamus cells. Vasopressin, it turns out regulates water in our body through the kidney. This constitutes the hypothalamic-pituitary-adrenal (HPA) axis. The HPA axis regulates a bunch of functions including our stress response, energy management, immune system and the digestive system.

This area can rapidly become extremely complicated if I'm not careful. One term for example sounds very interesting and I didn't pay attention to earlier, is neuroendocrine neurons. These are basically endocrine glands, except they are cells(neurons) that respond to neural stimuli. The hypothalamus has a lot of these. Other relevant neuroscience jargon are plasticity and the limbic system. Plasticity describes the capability of the adult brain to learn from experience and the limbic system is the part of the brain that differentiates us from other animals.

Also, in the literature stress is distinguished from stimulation. For example, excessive GC like I mentioned above is harmful and forms the upper threshold, while concentrations slightly higher than the basal levels are stimulatory and helps us learn stuff. So, in response to a severe stressor, enhanced GC action is triggered; but the physiological functions are supposed to recover over time and when that is not allowed, GC actions starts becoming pathological. Whats not clear to me yet is whether in response to a severe stressor, GC concentration is increased or does it just act faster or for a longer period or perhaps a feedback controlled combination of all these. It is interesting to note that Sapolsky points out the necessity of understanding the ethological perspective of stressors as percieved by the subject.

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