Prostaglandins in the sickness syndrome

63woman-698962_960_720When you’re sick you also feel awful: no appetite, weak, sleepy, feverish, achy, and so on. This is called, appropriately so, the sickness syndrome.

Saper, Romanovsky & Scammell (2012) wrote a beautiful review of the neural circuits underlying this collection of symptoms. In a nutshell, the immune system releases cytokines to fight the inflammation, which in turn stimulate the release of prostaglandins. Prostaglandins bind to various areas in the brain to produce the sickness syndrome symptoms. Below are outlined four simplified brain circuits which the non-specialists can skip entirely.

  1. Prostaglandins in the median preoptic nucleus lead to a cascade involving dorsomedial hypothalamus, rostral medullary raphe and finally the spinal cord to produce fever by activating the brown adipose tissue.
  2. Prostaglandins in the preoptic area lead to the inhibition of the brain’s analgesic system involving the descending projections of the periaqueductal grey to spinal cord, thus promoting achiness.
  3. Prostaglandins in the meninges result in adenosine release in nucleus accumbens and ventrolateral preoptic nucleus which, downstream, end in inhibiting the arousal system to produce sleepiness.
  4. Prostaglandins in the arcuate nucleus lead to inhibition of several hypothalamic nuclei involved in promoting feeding, thereby producing anorexia.

The sickness syndrome and the role prostaglandins play in it has tremendous adaptive role, as it promotes rest and recuperation. So don’t blame them too much. And if you’re really done feeling sick, take some non-steroid anti-inflammatory drugs, like aspirin, which inhibit the prostaglandins’ synthesis very effectively. That’s how and why NSAIDs work.

Reference: Saper CB, Romanovsky AA & Scammell TE (26 Jul 2012). Neural Circuitry Engaged by Prostaglandins during the Sickness Syndrome. Nature Neuroscience, 15(8):1088-95. doi: 10.1038/nn.3159. Article | FREE Fulltext PDF

By Neuronicus, 21 December 2015

Pee now! NOW, I said! In a huge magnet. While we watch.

Photo credit: Free clipart from www.cliparthut.com
Photo credit: Free clipart from http://www.cliparthut.com

Like many studies that fill in unknown gaps in the body of knowledge, the paper below may not attract attention, except from the people in their narrow field. So let’s give it a little attention.

Michels et al. (2015) sought to map out the brain network underlying the control of urination using an fMRI scanner. They got 22 healthy adult males and they gave them furosemide, which is a diuretic, and then asked them to drink as much water as they want until they need to urinate. During this, “a condom catheter was attached to the penis of each subject” (p. 3370), to monitor the urine flow while in scanner. Then the testing would not start, oh no. The subjects were then submitted to an ultrasound to make sure the bladder was full. Then they were asked again how much they really needed to go pee. Then they go in the scanner in a supine position, where they are told to wait, then to imagine the starting of urination (but don’t pee just yet!), and finally, finally allowed to urinate. But then, cruelly, told to stop only 3 second into the act. And then the scanner cycle would repeat. Their champion peers (I cannot avoid the pun, I’m sorry) managed to pee 15 times in the scanner. I wonder how many subjects peed sans cue… (authors don’t mention that).

Fig. 1 from Michels et al. (2015) depicting the fMRI scan paradigm, which consisted of 2 randomly alternating blocks.
Fig. 1 from Michels et al. (2015) depicting the fMRI scan paradigm, which consisted of 2 randomly alternating blocks. SDV = strong desire to void.

Amazingly, under these conditions, there were seven men who could not urinate in the scanner. Authors call these non-voiders, or, as we commonly know them, the shy bladders or the bashful kidneys. Not surprisingly, non-voiders had lower activity in the pontine micturition center (PMC), a brain area, which, as its name implies, is responsible for urination. Also not surprisingly – for me at least, the authors find this interesting -, the non-voiders showed increased activity in the anterior midcingulate cortex (aMCC), which is an area involved in control. I guess you need some steely control to not pee after all that. The aMCC inhibits the urination-facilitation brain regions, such as the PMC.

Anyway, the main finding of the study is a detailed map of micturition supraspinal mechanisms, which consists of a slew of structures, each with its own function. I had never known how complicated peeing and not-peeing are until I read this paper. Jokes and cringes aside, this study is a welcome addition to understanding how we control our bodily functions and where to start looking when this control fails, shedding new light on the interplay between reflex and control.

Reference: Michels, L., Blok, B. F., Gregorini, F., Kurz, M., Schurch, B., Kessler, T. M., Kollias, S., & Mehnert, U. (October 2015, Epub Jun 26 2014). Supraspinal Control of Urine Storage and Micturition in Men-An fMRI Study. Cerebral Cortex, 25(10): 3369-80. doi: 10.1093/cercor/bhu140. Article | FREE FULLTEXT PDF

By Neuronicus, 1 October 2015