Schwann cell precursors generate sympathoadrenal system during zebrafish development.

The autonomic portion of the peripheral nervous system orchestrates tissue homeostasis through direct innervation of internal organs, and via release of adrenalin and noradrenalin into the blood flow. The developmental mechanisms behind the formation of autonomic neurons and chromaffin cells are not fully understood. Using genetic tracing, we discovered that a significant proportion of sympathetic neurons in zebrafish originates from Schwann cell precursors (SCPs) during a defined period of embryonic development. Moreover, SCPs give rise to the main portion of the chromaffin cells, as well as to a significant proportion of enteric and other autonomic neurons associated with internal organs. The conversion of SCPs into neuronal and chromaffin cells is ErbB receptor dependent, as the pharmacological inhibition of the ErbB pathway effectively perturbed this transition. Finally, using genetic ablations, we revealed that SCPs producing neurons and chromaffin cells migrate along spinal motor axons to reach appropriate target locations. This study reveals the evolutionary conservation of SCP-to-neuron and SCP-to-chromaffin cell transitions over significant growth periods in fish and highlights relevant cellular-genetic mechanisms. Based on this, we anticipate that multipotent SCPs might be present in postnatal vertebrate tissues, retaining the capacity to regenerate autonomic neurons and chromaffin cells.

Familial Mediterranean fever: the molecular pathways from stress exposure to attacks.

FMF is an autoinflammatory disease characterized by recurrent attacks and increased IL-1 synthesis owing to activation of the pyrin inflammasome. Although knowledge of the mechanisms leading to the activation of pyrin inflammasome is increasing, it is still unknown why the disease is characterized by attack. The emergence of FMF attacks after emotional stress and the induction of attacks with metaraminol in previous decades suggested that stress-induced sympathoadrenal system activation might play a role in inflammasome activation and triggering attacks. In this review, we will review the possible molecular mechanism of stress mediators on the inflammation pathway and inflammasome activation. Studies on stress mediators and their impact on inflammation pathways will provide a better understanding of stress-related exacerbation mechanisms in both autoinflammatory and autoimmune diseases. This review provides a new perspective on this subject and will contribute to new studies.

The longevity gene mIndy (I'm Not Dead, Yet) affects blood pressure through sympathoadrenal mechanisms.

Reduced expression of the plasma membrane citrate transporter INDY (acronym I'm Not Dead, Yet) extends life span in lower organisms. Deletion of the mammalian Indy (mIndy) gene in rodents improves metabolism via mechanisms akin to caloric restriction, known to lower blood pressure (BP) by sympathoadrenal inhibition. We hypothesized that mIndy deletion attenuates sympathoadrenal support of BP. Continuous arterial BP and heart rate (HR) were reduced in mINDY-KO mice. Concomitantly, urinary catecholamine content was lower, and the decreases in BP and HR by mIndy deletion were attenuated after autonomic ganglionic blockade. Catecholamine biosynthesis pathways were reduced in mINDY-KO adrenals using unbiased microarray analysis. Citrate, the main mINDY substrate, increased catecholamine content in pheochromocytoma cells, while pharmacological inhibition of citrate uptake blunted the effect. Our data suggest that deletion of mIndy reduces sympathoadrenal support of BP and HR by attenuating catecholamine biosynthesis. Deletion of mIndy recapitulates beneficial cardiovascular and metabolic responses to caloric restriction, making it an attractive therapeutic target.