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International audience; The central nervous system (CNS) monitors modifications in metabolic parameters or hormone levels and elicits adaptive responses such as food intake regulation. Particularly, within the hypothalamus, leptin modulates the activity of pro-opiomelanocortin (POMC) neurons which are critical regulators of energy balance. Consistent with a pivotal role of the melanocortin system in the control of energy homeostasis, disruption of the POMC gene causes hyperphagia and obesity. MicroRNAs (miRNAs) are short noncoding RNA molecules that post-transcriptionally repress the expression of genes by binding to 3 ′-untranslated regions (3 ′ UTR) of the target mRNAs. However, little is known regarding the role of miRNAs that target POMC 3 ′ UTR in the central control energy homeostasis. Particularly, their interaction with the leptin signaling pathway remain unclear. First, we used common prediction programs to search for potential miRNAs target sites on 3 ′ UTR of POMC mRNA. This screening identified a set of conserved miRNAs seed sequences for mir-383, mir-384-3p, and mir-488. We observed that mir-383, mir-384-3p, and mir-488 are up-regulated in the hypothalamus of leptin deficient ob/ob mice. In accordance with these observations, we also showed that mir-383, mir-384-3p, and mir-488 were increased in db/db mice that exhibit a non-functional leptin receptor. The intraperitoneal injection of leptin down-regulated the expression of these miRNAs of interest in the hypothalamus of ob/ob mice showing the involvement of leptin in the expression of mir-383, mir-384-3p, and mir-488. Finally, the evaluation of responsivity to intracerebroventricular administration of leptin exhibited that a chronic treatment with leptin decreased mir-488 expression in hypothalamus of C57BL/6 mice. In summary, these results suggest that leptin modulates the expression of miRNAs that target POMC mRNA in hypothalamus.

International audience; Cerebrospinal fluid (CSF) contacting neurones have been observed in various brain regions such as the hypothalamus, the dorsal nucleus of the raphe and around the central canal (cc) of the spinal cord but their functional role remains unclear. At the level of the spinal cord, subependymal cerebrospinal fluid contacting neurones (S-CSF-cNs) present a peculiar morphology with a soma close to the ependymal layer, a process projecting towards the cc and ending with a bud and a cilium. These neurones were recently shown to express polycystin kidney disease 2-like 1 (PKD2L1 or TRPP3) channels that are members of the polycystin subtype of the transient receptor potential (TRP) channel superfamily and that have been proposed as either chemo- or mechanoreceptors in several tissues. Using immunohistological techniques and whole-cell electrophysiological recordings in brain slices obtained from PKD2L1:EGFP transgenic adult mice, we looked for and determined the functional properties of S-CSF-cNs in the dorsal vagal complex (DVC), a hindbrain structure controlling autonomic functions such as blood pressure, energy balance and food intake. Here, we demonstrate that S-CSF-cNs received GABAergic and/or glycinergic synaptic entries and were also characterised by the presence of non-selective cationic channels of large conductance that could be detected even under whole-cell configuration. The channel activity was not affected by Psalmopoeus cambridgei toxin 1, a blocker of acid sensing ion channels (ASICs), but was blocked by amiloride and by a strong extracellular acidification. In contrast, extracellular alkalinisation and hypo-osmotic shocks increased channel activity. Based on these properties, we suggest that the single-channel activity recorded in medullar S-CSF-cNs is carried by PKD2L1 channels. Our study therefore reinforces the idea that PKD2L1 is a marker of S-CSF-cNs and points toward a role for S-CSF-cNs in the detection of circulating signals and of modifications in the extracellular environment.