Hepcidin induces intestinal calcium uptake while suppressing iron uptake in Caco-2 cells

Abnormal calcium absorption and iron overload from iron hyperabsorption can contribute to osteoporosis as found in several diseases, including hemochromatosis and thalassemia. Previous studies in thalassemic mice showed the positive effects of the iron uptake suppressor, hepcidin, on calcium transport. However, whether this effect could be replicated in other conditions is not known. Therefore, this study aimed to investigate the effects of hepcidin on iron and calcium uptake ability under physiological, iron uptake stimulation and calcium uptake suppression. To investigate the potential mechanism, effects of hepcidin on the expression of iron and calcium transporter and transport-associated protein in Caco-2 cells were also determined. Our results showed that intestinal cell iron uptake was significantly increased by ascorbic acid together with ferric ammonium citrate (FAC), but this phenomenon was suppressed by hepcidin. Interestingly, hepcidin significantly increased calcium uptake under physiological condition but not under iron uptake stimulation. While hepcidin significantly suppressed the expression of iron transporter, it had no effect on calcium transporter expression. This indicated that hepcidin-induced intestinal cell calcium uptake did not occur through the stimulation of calcium transporter expression. On the other hand, 1,25(OH)2D3 effectively induced intestinal cell calcium uptake, but it did not affect intestinal cell iron uptake or iron transporter expression. The 1,25(OH)2D3-induced intestinal cell calcium uptake was abolished by 12 mM CaCl2; however, hepcidin could not rescue intestinal cell calcium uptake suppression by CaCl2. Taken together, our results showed that hepcidin could effectively and concurrently induce intestinal cell calcium uptake while reducing intestinal cell iron uptake under physiological and iron uptake stimulation conditions, suggesting its therapeutic potential for inactive calcium absorption, particularly in thalassemic patients or patients who did not adequately respond to 1,25(OH)2D3.

Dynamic properties of mitochondria during human corticogenesis

ABSTRACTMitochondria are signaling hubs responsible for the generation of energy through oxidative phosphorylation, the production of key metabolites that serve the bioenergetic and biosynthetic needs of the cell, calcium (Ca2+) buffering and the initiation/execution of apoptosis. The ability of mitochondria to coordinate this myriad of functions is achieved through the exquisite regulation of fundamental dynamic properties, including remodeling of the mitochondrial network via fission and fusion, motility and mitophagy. In this Review, we summarize the current understanding of the mechanisms by which these dynamic properties of the mitochondria support mitochondrial function, review their impact on human cortical development and highlight areas in need of further research.

Zona Incerta subpopulations differentially encode and modulate anxiety

Despite recent clinical observations linking the Zona Incerta (ZI) to anxiety, little is known about whether and how the ZI processes anxiety. Here, we subject mice to anxious experiences and observe an increase in ZI cfos-labelled neurons and single-cell calcium activity as well as an efficient effect of ZI infusion of diazepam a classical anxiolytic drug. We further identify that somatostatin-(SOM), calretinin-(CR), and vesicular glutamate transporter-2 (Vglut2)-expressing cells display unique electrophysiological profiles; yet they similarly respond to anxiety-provoking stimuli and to diazepam. Interestingly, optogenetic manipulations reveals that each of these ZI neuronal population triggers specific anxiety-related behavioral phenotypes. Activation of SOM-expressing neurons induced anxiety while in stark contrast, photo-activation of CR-positive cells and photo-inhibition of Vglut2-expressing neurons produce anxiolysis. Furthermore, activation of CR- and Vglut2-positive cells provokes rearing and jumps; respectively. Our findings provide the first experimental evidence that ZI subpopulations encode and modulate different components of anxiety.