Neural excitability, synaptic transmission and neuron-glia interactions
Author: Giovanna Margarita Velázquez Campos | Email: gvelazquez.010390@gmail.com
Giovanna Margarita Velázquez-Campos1°2°, Magdalena Fernández-Acosta1°,María lucia Mares1°, María Fernanda Ceriani1°
1° Fundación Instituto Leloir IIB-BA/CONICET
2° Biología Molecular y Biotecnología de la Universidad Nacional de General San Martín
The circadian clock plays a crucial role in maintaining lipid homeostasis. However, whether lipid signalling feedbacks to the clock has not been addressed. To explore the impact of lipid metabolism on the molecular clock we investigated the role of Osi, a key regulator of lipid catabolism, in the adult brain. Adult-specific osi knockdown (osiKD) in a subset of pacemaker neurons (LNvs) prolongs the free-running period, which results from an altered pace of the molecular clock. Interestingly, the period phenotype is rescued by expression of ETFRF1, the human ortholog of osi that modulates beta-oxidation. osi mutants have elevated ROS levels; however, neither the antioxidant administration NAC nor SOD2 overexpression were effective in rescuing the phenotypes. We next explored whether abnormal signalling could underlie circadian deficits. Lipase 3 (Lip 3) rescues the phenotypes associated to Osi dysfunction in the fat body. However, Lip3 downregulation in neurons does not alleviate the circadian phenotypes resulting from osiKD. Instead, Lip3 knockdown alone leads to a similar period lengthening, suggesting that both proteins may act on the same pathway; if so, Osi would regulate phosphoinositol levels in the brain. In favor of this possibility, the morphology of the sLNv terminals is affected upon osiKD. These results suggest that Osi plays a fundamental role in LNv physiology and provides an opportunity to analyze the cross-talk between lipid metabolism and the circadian clock.