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 4 simplified circuits which the non-specialists can skip entirely.

  1. in median preoptic nucleus which will 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. in preoptic area which will 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. in the meninges that results in adenosine release which binds in nucleus accumbens and ventrolateral preoptic nucleus which will result, downstream, in inhibiting the arousal system to produce sleepiness.
  4. in arcuate nucleus to inhibit 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, who very effectively inhibit the prostaglandins’ synthesis. That’s 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

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Putative mechanism for decreased spermatogenesis following SSRI

fishThe SSRIs (selective serotonin reuptake inhibitors) are the most commonly prescribed antidepressants around the world. Whether is Prozac, Zoloft or Celexa, chances are that 1 in 4 Americans (or 1 in 10, depending on the study) will be making a decision during their lifetime to start an antidepressant course or not. And yet adherence to treatment is significantly low, as many people get off the SSRI due to their side effects, one of the main complains being sexual dysfunction in the form of low libido and pleasure.

Now a new study finds a mechanism for an even more worrisome effect of citalopram, (Celexa), an SSRI: the reduction of spermatogenesis. Prasad et al. (2015) used male zebrafish as a model and exposed them to citalopram in 3 different doses for 2- or 4-weeks period. They found out that the expression in the brain of the serotonin-related genes (trp2 and sert) and gonadotropin genes (lhb, sdhb, gnrh2, and gnrh3) were differently affected depending on the dose and durations of treatment. In the testes, the “long-term medium- and high-dose citalopram treatments displayed a drastic decrease in the developmental stages of spermatogenesis as well as in the matured sperm cell count” (p. 5). The authors also looked at how the neurons are organized and they found out that the serotonin fibers are associated with the fibers of the neurons that release gonadotropin-releasing hormone 3 (GnRH3) in preoptic area, a brain region in the hypothalamus heavily involved in sexual and parental behavior in both humans and fish.

Shortly put, in the brain, the citalopram affects gene expression profiles and fiber density of the serotonin neurons, which in turn decreases the production of GnRH3, which may account for the sexual dysfunctions that follow citalopram. In the testes, citalopram may act directly by binding to the local serotonin receptors and decrease spermatogenesis.

Reference: Prasad P, Ogawa S, & Parhar IS. (Oct 2015, Epub 8 Jul 2015). Serotonin Reuptake Inhibitor Citalopram Inhibits GnRH Synthesis and Spermatogenesis in the Male Zebrafish. Biololy of Reproduction. 93(4):102, 1-10. doi: 10.1095/biolreprod.115.129965. Article | FREE FULLTEXT PDF

By Neuronicus, 11 November 2015