title: Leptin counteracts the hypoxia-induced inhibition of spontaneously firing hippocampal neurons: a microelectrode array study.
abstract: Besides regulating energy balance and reducing body-weight, the adipokine leptin has been recently shown to be neuroprotective and antiapoptotic by promoting neuronal survival after excitotoxic and oxidative insults. Here, we investigated the firing properties of mouse hippocampal neurons and the effects of leptin pretreatment on hypoxic damage (2 hours, 3% O(2)). Experiments were carried out by means of the microelectrode array (MEA) technology, monitoring hippocampal neurons activity from 11 to 18 days in vitro (DIV). Under normoxic conditions, hippocampal neurons were spontaneously firing, either with prevailing isolated and randomly distributed spikes (11 DIV), or with patterns characterized by synchronized bursts (18 DIV). Exposure to hypoxia severely impaired the spontaneous activity of hippocampal neurons, reducing their firing frequency by 54% and 69%, at 11 and 18 DIV respectively, and synchronized their firing activity. Pretreatment with 50 nM leptin reduced the firing frequency of normoxic neurons and contrasted the hypoxia-induced depressive action, either by limiting the firing frequency reduction (at both ages) or by increasing it to 126% (in younger neurons). In order to find out whether leptin exerts its effect by activating large conductance Ca(2+)-activated K(+) channels (BK), as shown on rat hippocampal neurons, we applied the BK channel blocker paxilline (1 µM). Our data show that paxilline reversed the effects of leptin, both on normoxic and hypoxic neurons, suggesting that the adipokine counteracts hypoxia through BK channels activation in mouse hippocampal neurons.
authors: Department of Drug Science and Technology, NIS Center, CNISM, University of Torino, Torino, Italy.
authors: Daniela
authors: D
authors: Gavello
authors: Jonathan
authors: J
authors: Rojo-Ruiz
authors: Andrea
authors: A
authors: Marcantoni
authors: Claudio
authors: C
authors: Franchino
authors: Emilio
authors: E
authors: Carbone
authors: Valentina
authors: V
authors: Carabelli
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D020738:Leptin / Q000494:pharmacology*; D051379:Mice; D026902:Potassium Channel Blockers / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D007211:Indoles; D051036:Large-Conductance Calcium-Activated Potassium Channels; D020738:Leptin; D026902:Potassium Channel Blockers; C048220:paxilline