Scavenging of reactive oxygen species mimics the anoxic response in goldfish pyramidal neurons

Abstract

Goldfish are one of a few species able to avoid cellular damage during month-long periods in severely hypoxic environments. By suppressing action potentials in excitatory glutamatergic neurons, the goldfish brain decreases its overall energy expenditure. Co-incident with reductions in O2 availability is a natural decrease in cellular reactive oxygen species (ROS) generation, which has been proposed to function as part of a low oxygen signal transduction pathway. Therefore, using live-tissue fluorescence microscopy, we found that ROS production decreased by 10% with the onset of anoxia in goldfish telencephalic brain slices. Employing whole-cell patch-clamp recording, we found that like severe hypoxia the ROS scavengers N-acetyl cysteine (NAC) and MitoTEMPO, added during normoxic periods, depolarized membrane potential (severe hypoxia -73.6 to – 61.4 mV; NAC -76.6 to -66.2 mV; and MitoTEMPO -71.5 mV to -62.5 mV) and increased whole-cell conductance (severe hypoxia 5.7 to 8.0 nS; NAC 6 nS to 7.5 nS; and MitoTEMPO 6.0 nS to 7.6 nS). Also, in a subset of active pyramidal neurons these treatments reduced action potential firing frequency (severe hypoxia 0.18 Hz to 0.03 Hz; NAC 0.27 Hz to 0.06 Hz and MitoTEMPO 0.35 Hz to 0.08 Hz ). Neither severe hypoxia nor ROS scavenging impacted action potential threshold. The addition of exogenous hydrogen peroxide could reverse the effects of the antioxidants. Taken together, this supports a role for a reduction in [ROS] as a low oxygen signal in goldfish brain.

Alfaxalone does not have long‐term effects on goldfish pyramidal neuron action potential properties or GABAA receptor currents

“…Previous average membrane potential and whole‐cell conductance values for the common goldfish were found to be −72.18 ± 2.3 mV and 3.96 ± 0.95 nS respectively [54]. Similar average membrane potential and whole‐cell conductance values were later found to be −72.33 ± 3.35 mV and 3.95 ± 0.36 nS respectively [60]. In comparison, our study found average membrane potential and whole‐cell conductance values of −68.2 ± 1.77 mV and 3.53 ± 0.370 nS in naïve/control tissue and − 70.0 ± 1.91 mV and 3.86 ± 0.386 nS in tissue derived following whole‐animal alfaxalone sedation.…”