Summary: Researchers have discovered a potential new way to reduce levels of hydrogen sulfide in rats’ brains. Decreasing H2S levels decreases the damage the toxic gas can cause, and ultimately may pave the way for the development of new treatments for dementia and epilepsy.
Source: University of Reading
A potential treatment for dementia and epilepsy could look to reduce the amounts of a toxic gas in the brain has been revealed in a new study using rat brain cells.
The research published in Scientific Reports today shows that treatments to reduce levels of hydrogen sulfide (H2S) in the brain may help to ward off damage caused by the gas.
By testing rat brain cells, the team of scientists from the University of Reading, University of Leeds and John Hopkins University in the USA found that H2S is involved in blocking a key brain cell gateway that helps the brain to communicate effectively.
Dr Mark Dallas, Associate Professor in Cellular Neuroscience at the University of Reading said:
“This is an exciting finding as it gives us new insights about the role of hydrogen sulfide in various brain diseases, such as dementia and epilepsy. There has been growing interest in the effect of hydrogen sulfide on the brain and this study shows how important the implications of its build-up on proper brain functioning may be.
“We saw that hydrogen suldife acts to disrupt the normal functioning of potassium channels. These channels regulate electrical activity across the connections between brain cells, and when these channels are blocked from working properly we see overexcitable brain cells which we believe is leading to nerve cell death.
“The implication for potential treatments is particularly exciting because finding drugs that target hydrogen sulfide production in our brains may have a host of benefits for diseases, and there are clear links between hydrogen sulfide build -up and other warning signs for diseases such as Alzheimer’s.”
In the study, cells taken from rat brains were charged with a H2S donor molecule, and then brain cell electrical signals were monitored. The resulting exposure to H2S increased the level of activity in brain cells, and the research was able to establish that the effect was specifically controlled by the potassium channel tested.
The team were also able to identify which part of the potassium channel was allowing this effect from H2S. They used a mutated form of the potassium channel, which has already been shown to protect nerve cells from a host of toxic stimuli, including amyloid beta and found that the mutation was resistant to the effect of H2S that was seen in natural cells.
The specific mutated channel now holds particular interest for research into Alzheimer’s Disease, given the protective benefits against amyloid beta which is also implicated in dementia.
Dr Moza Al-Owais, Research Fellow at the University of Leeds said:
“This exciting study demonstrates the growing evidence that gasotransmitters play an important role as signalling molecules in the regulation of the physiological processes underlying Alzheimer’s disease, which are relatively poorly understood, opening new avenues for investigation and drug discovery.”
About this neurology research news
Source: University of Reading Contact: Tim Mayo – University of Reading Image: The image is in the public domain
Hydrogen sulfide regulates hippocampal neuron excitability via S-sulfhydration of Kv2.1
Hydrogen sulfide (H2S) is gaining interest as a mammalian signalling molecule with wide ranging effects. S-sulfhydration is one mechanism that is emerging as a key post translational modification through which H2S acts.
Ion channels and neuronal receptors are key target proteins for S-sulfhydration and this can influence a range of neuronal functions. Voltage-gated K+ channels, including Kv2.1, are fundamental components of neuronal excitability.
Here, we show that both recombinant and native rat Kv2.1 channels are inhibited by the H2S donors, NaHS and GYY4137. Biochemical investigations revealed that NaHS treatment leads to S-sulfhydration of the full length wild type Kv2.1 protein which was absent (as was functional regulation by H2S) in the C73A mutant form of the channel.
Functional experiments utilising primary rat hippocampal neurons indicated that NaHS augments action potential firing and thereby increases neuronal excitability.
These studies highlight an important role for H2S in shaping cellular excitability through S-sulfhydration of Kv2.1 at C73 within the central nervous system.