Inhibition of the Jak-STAT pathway prevents CNTF-mediated survival of axotomized oxytocinergic magnocellular neurons in organotypic cultures of the rat supraoptic nucleus.

Previous studies have demonstrated that ciliary neurotrophic factor (CNTF) enhances survival and process outgrowth from magnocellular neurons in the paraventricular (PVN) and the supraoptic (SON) nuclei. However, the mechanisms by which CNTF facilitates these processes remain to be determined. Therefore, the aim of this study was to identify the immediate signal transduction events that occur within the rat SON following administration of exogenous rat recombinant CNTF (rrCNTF) and to determine the contribution of those intracellular signaling pathway(s) to neuronal survival and process outgrowth, respectively. Immunohistochemical and Western blot analyses demonstrated that axonal injury and acute unilateral pressure injection of 100 ng/µl of rrCNTF directly over the rat SON resulted in a rapid and transient increase in phosphorylated-STAT3 (pSTAT3) in astrocytes but not neurons in the SON in vivo. Utilizing rat hypothalamic organotypic explant cultures, we then demonstrated that administration of 25 ng/ml rrCNTF for 14days significantly increased the survival and process outgrowth of OT magnocellular neurons. In addition, pharmacological inhibition of the Jak-STAT pathway via AG490 and cucurbitacin I significantly reduced the survival of OT magnocellular neurons in the SON and PVN; however, the contribution of the Jak-STAT pathway to CNTF-mediated process outgrowth remains to be determined. Together, these data indicate that CNTF-induced survival of OT magnocellular neurons is mediated indirectly through astrocytes via the Jak-STAT signaling pathway.

Massive gastric dilation and necrosis in anorexia nervosa: cause or effect?

A 26-year-old female with a diagnosis of anorexia nervosa was admitted and found to have massive gastric dilation and gastric necrosis. Imaging studies suggested the possibility of superior mesenteric artery (SMA) syndrome. She was successfully managed with prompt gastric decompression and was able to resume oral nutrition. Gastric dilation and necrosis may be seen in anorexia nervosa as either an independent event or an SMA syndrome. The SMA syndrome may also be present as either an incidental finding or a true pathophysiologic entity. Finally, significant foregut dysfunction may be mistaken for an eating disorder. Although there is clearly an association between gastric dilation, the SMA syndrome, and eating disorders, cause and consequence may not always be straightforward. Prompt recognition and conservative management are advocated in the absence of abdominal catastrophe.