Effects of Hydrogen Sulfide on Modulation of Theta-Gamma Coupling in Hippocampus in Vascular Dementia Rats

Brain Topogr. 2015 Nov;28(6):879-94. doi: 10.1007/s10548-015-0430-x. Epub 2015 Mar 14.


Our previous study showed that hydrogen sulfide (H2S) could alleviate the cognitive deficits in vascular dementia (VD) rats associated with the improvement of synaptic plasticity. Neural oscillations are reported to interact with each other through either identical-frequency or cross-frequency coupling. This study examined whether impaired neural couplings could be alleviated by H2S in the hippocampal CA3-CA1 of VD rats and explored its possible mechanism. A VD rat model was established by two-vessel occlusion. Sodium hydrosulfide (NaHS), a kind of H2S donor, was administered intraperitoneally (5.6 mg/kg/day) for 3 weeks. Local field potentials were simultaneously collected in the hippocampal CA3 and CA1. The effects of NaHS on the modulation of theta-gamma coupling were evaluated by using the measurements of both phase-phase coupling and phase-amplitude coupling, while several other approaches including behavior, electrophysiology, western blot, immunofluorescence staining were also employed. The results showed that NaHS significantly prevented spatial learning and memory impairments (p < 0.01). NaHS considerably alleviated the impairment of neural coupling in VD rats in an identical-frequency rhythm and between cross-frequency bands. Moreover, the expression of cystathionine-β-synthase (CBS) was markedly attenuated in VD rats. NaHS elevated the expression of CBS to maintain the intrinsic balance of H2S. Interestingly, it was observed that NaHS increased the protein expression of N-methyl-D-aspartic acid receptor 2A (NMDAR2A) in VD rats. In conclusion, the data suggest that NaHS played the neuroprotective role partly via modulating the expression of NMDAR2A in order to alleviate the impairments of neural couplings in VD rats.

Keywords: Cross frequency coupling; Gamma; Hydrogen sulfide; Identical frequency coupling; Theta; Vascular dementia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Waves / drug effects*
  • Dementia, Vascular / drug therapy*
  • Dementia, Vascular / pathology*
  • Disease Models, Animal
  • Electrodes, Implanted
  • Electroencephalography
  • Gasotransmitters / pharmacology
  • Gasotransmitters / therapeutic use*
  • Hippocampus / drug effects*
  • Hydrogen Sulfide / pharmacology
  • Hydrogen Sulfide / therapeutic use*
  • Male
  • Maze Learning / drug effects
  • Rats
  • Rats, Wistar
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Time Factors


  • Gasotransmitters
  • Receptors, N-Methyl-D-Aspartate
  • N-methyl D-aspartate receptor subtype 2A
  • Hydrogen Sulfide