CELLULAR ACTIONS OF ASTAXANTHIN ON MOUSE HYPOTHALAMUS
01/29/2020
Andrea Csemer1, 2, Krisztina Pocsai1, 2, Mónika Sztretye2, Tsogbadrakh Bayasgalan2, Adrienn Kovács2, Péter Szücs3, László Csernoch2, Balázs Pál2
2 Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, 4032, Hungary
3 Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, Debrecen, 4032, Hungary
Astaxanthin is a carotenoid synthesized by bacteria and algae and widely found in seafood. This molecule is known from its powerful antioxidant and anti-inflammatory actions. In this project we aimed to investigate actions of astaxanthine on food intake and energy homeostasis and the cellular background of its actions. We found that feeding mice with astaxanthin-rich chow resulted significantly limited weight gain compared to the control group fed with normal chow. Investigating the cellular background of this finding, we conducted slice electrophysiology and imaging experiments on the arcuate nucleus of feeded and control mice, as well as on mice expressing tdTomato under POMC- or GAD2 promoter and GCaMP6 under Vgat2 promoter. We found that neurons of astaxanthin-feeded mice displayed significantly greater frequency of spontaneous inhibitory postsynaptic currents (sIPSC). Similar, although weaker frequency increase was seen on POMC-positive neurons when astaxanthin was applied to the recording chamber.Next, we investigated actions on GABAergic neurons in the arcuate nucleus, which are potentially responsible for the sIPSC frequency increase. We found that 77% of the GABAergic neurons increased the frequency of calcium transients, and a subpopulation of GABAergic neurons showed increased excitability and received excitatory postsynaptic currents (EPSCs) with a greater frequency. Actions of astaxanthin on arcuate nucleus seems to be a network effect with multiple targets including excitability of local GABAergic neurons and excitatory inputs on them. These network actions might serve as the potential background of changes in energy homeostasis. Supported by the Higher Education Institutional Excellence Programme (NKFIH-1150-6/2019) of the Ministry of Innovation and Technology in Hungary, Therapeutic-based Thematic Program