Abstract
Hydrogen sulfide (H2S) is an endogenously produced neuroactive gas implicated in many key processes in the peripheral and central nervous system. Whereas the neuroprotective role of H2S has been shown in adult brain, the action of this messenger in newborns remains unclear. One of the known targets of H2S in the nervous system is the N-methyl-D-aspartate (NMDA) glutamate receptor which can be composed of different subunits with distinct functional properties. In the present study, using patch clamp technique, we compared the effects of the H2S donor sodium hydrosulfide (NaHS, 100 μM) on hippocampal NMDA receptor mediated currents in rats of the first and third postnatal weeks. This was supplemented by testing effects of NaHS on recombinant GluN1/2A and GluN1/2B NMDA receptors expressed in HEK293T cells. The main finding is that NaHS action on NMDA currents is age-dependent. Currents were reduced in newborns but increased in older juvenile rats. Consistent with an age-dependent switch in NMDA receptor composition, in HEK239T cells expressing GluN1/2A receptors, NaHS increased NMDA activated currents associated with acceleration of desensitization and decrease of the deactivation rate. In contrast, in GluN1/2B NMDA receptors, which are prevalent in newborns, NaHS decreased currents and reduced receptor deactivation without effect on the desensitization rate. Adenylate cyclase inhibitor MDL-12330A (10 μM) did not prevent the age-dependent effects of NaHS on NMDA evoked currents in pyramidal neurons of hippocampus. The reducing agent dithiothreitol (DTT, 2 mM) applied on HEK293T cells prevented facilitation induced by NaHS on GluN1/2A NMDA receptors, however in GluN1/2B NMDA receptors the inhibitory effect of NaHS was still observed. Our data indicate age-dependent effect of H2S on NMDA receptor mediated currents determined by glutamate receptor subunit composition. While the inhibitory action of H2 on GluN1/2B receptors could limit the excessive activation in early age, the enhanced functionality of GluN1/2A receptor in the presence of this gasotransmitter can enlarge synaptic efficacy and promote synaptic plasticity in adults.
Highlights
Hydrogen sulfide (H2S) is a member of gasotransmitters family involved in the regulation of neuronal plasticity, excitability and neurotransmitter release in the peripheral and central nervous system (Abe and Kimura, 1996; Wang, 2012; Gerasimova et al, 2015; Yakovlev et al, 2017)
It is known that the subunit composition of NMDA receptors in rodent hippocampus is changing during postnatal development (Chang et al, 2009)
Whole cell recordings from pyramidal neurons were performed at a holding potential of −60 mV and 100 μM NMDA + 30 μM glycine was locally applied from the puff pipettes
Summary
Hydrogen sulfide (H2S) is a member of gasotransmitters family involved in the regulation of neuronal plasticity, excitability and neurotransmitter release in the peripheral and central nervous system (Abe and Kimura, 1996; Wang, 2012; Gerasimova et al, 2015; Yakovlev et al, 2017). H2S can be produced from cysteine by D-amino acid oxidase (DAO) or 3-mercaptopyruvate sulfurtransferase (3-MST) in combination with cysteine aminotransferase (CAT; Shibuya et al, 2009, 2013; Kimura, 2014). It has been shown, that H2S produces anti-inflammatory, antioxidant and antiapoptotic effects in glial and neuronal cells (Lee et al, 2010; Kamat et al, 2015). In neonatal brain H2S abolished interictal-like events induced by bicuculline preventing enhanced neuronal excitability typical to early hippocampal networks (Yakovlev et al, 2017)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
