Hydrogen Sulfide Alleviates Anxiety, Motor, and Cognitive Dysfunctions in Rats with Maternal Hyperhomocysteinemia via Mitigation of Oxidative Stress

Abstract

<jats:p>Hydrogen sulfide (H2S) is endogenously produced from sulfur containing amino acids, including homocysteine and exerts neuroprotective effects. An increase of homocysteine during pregnancy impairs fetal growth and development of the offspring due to severe oxidative stress. We analyzed the effects of the H2S donor—sodium hydrosulfide (NaHS) administered to female rats with hyperhomocysteinemia (hHcy) on behavioral impairments and levels of oxidative stress of their offspring. Rats born from females fed with control or high methionine diet, with or without H2S donor injections were investigated. Rats with maternal hHcy exhibit increased levels of total locomotor activity and anxiety, decreased muscle endurance and motor coordination, abnormalities of fine motor control, as well as reduced spatial memory and learning. Oxidative stress in brain tissues measured by activity of glutathione peroxidases and the level of malondialdehyde was higher in rats with maternal hHcy. Concentrations of H2S and the activity and expression of the H2S generating enzyme—cystathionine-beta synthase—were lower compared to the control group. Administration of the H2S donor to females with hHcy during pregnancy prevented behavioral alterations and oxidative stress of their offspring. The acquisition of behavioral together with biochemical studies will add to our knowledge about homocysteine neurotoxicity and proposes H2S as a potential agent for therapy of hHcy associated disorders.</jats:p>

High Methionine Diet-Induced Alzheimer’s Disease like Symptoms Are Accompanied by 5-Methylcytosine Elevated Levels in the Brain

“…In addition, the CA3 and DG areas of the hippocampus participate in spatial learning and memory, which are important for the maintenance of hippocampal function. Furthermore, it has been demonstrated that HMD reduces the neurons number in the CA3 and DG [ 52 , 53 ], suggesting that these data help to understand the impact of HMD on changes in the nervous system. Although these effects are consistent with our results, they did not clarify the relationship between HMD-induced AD-like symptoms and 5-mC as in this work.…”

GluN2 Subunit-Dependent Redox Modulation of NMDA Receptor Activation by Homocysteine

“…Therefore, the redox status of NMDARs may govern the contribution of GluN2A and GluN2B subunit-containing receptors to HCY-caused neurotoxicity, which is an unexpected conclusion. This observation can provide some clues as to why treatment with reducing reagents like hydrogen sulfide (H 2 S) rescues NMDAR expressing neuroblastoma cells [ 44 ], neurons [ 45 ], and prevents behavioral alterations [ 46 ] in hyperhomocysteinemia.…”

The role of brain gaseous neurotransmitters in anxiety

“…Also 3-mercaptopyruvate sulfurtransferase (MPST) is involved in brain H 2 S synthesis from 3-mercaptopyruvate (3-MPT). Of note, an interesting crosstalk between NO and CO pathways may regulate heme moiety of CBS has recently been suggested [ 107 – 109 ]. A non-enzymatic reaction of H 2 S synthesis which is catalyzed by pyridoxal 5′-phosphate (vitamin B6) and iron may also occur in some tissues especially within erythrocytes [ 110 ].…”