Conclusions
These findings indicate that the auto-excitatory effect of OT on OT neurons is mediated by H2S from astrocytes at least partially and astrocytic H2S can elicit retraction of astrocytic processes that subsequently increase OT neuronal excitability.
Methods
In hypothalamic slices of male rats, OT and H2S-associated drug effects were observed on the firing activity and spontaneous excitatory postsynaptic currents (sEPSCs) of putative OT neurons in the supraoptic nucleus (SON) in whole-cell patch-clamp recording. Expression of glial fibrillary acidic protein (GFAP) in the SON was analyzed in Western blots. In addition, changes in the length of rat pups' hypothalamic astrocytic processes were observed in primary cultures.
Results
In brain slices, OT significantly increased the firing rate of OT neurons, which was simulated by CBS allosteric agonist S-adenosyl-L-methionine (SAM) and H2S slow-releasing donor GYY4137 but blocked by CBS inhibitor aminooxyacetic acid (AOAA). L-α-aminoadipic acid (a gliotoxin) blocked SAM-evoked excitation. OT and SAM also increased the frequency and amplitude of sEPSCs; the effect of OT was blocked by AOAA. Both OT and GYY4137 reduced GFAP expression in the SON. Morphologically, OT or GYY4137 time-dependently reduced the length of astrocytic processes in primary cultures. Conclusions: These findings indicate that the auto-excitatory effect of OT on OT neurons is mediated by H2S from astrocytes at least partially and astrocytic H2S can elicit retraction of astrocytic processes that subsequently increase OT neuronal excitability.