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.