Beware smelly gutters: hydrogen sulphide can hurt your brain

news
09 January 2015

An Indian-origin researcher in the US has led a study that finds hydrogen sulphide, a short-lived gas produced in the human body, can impact the brain's ability to use food and glucose and result in memory loss.

Researchers at Georgia Regents University in the US found that the immune cell interleukin 1 beta, or IL-1 beta, prompts production of hydrogen sulphide a stinking and highly poisonous gas that gives out the odour of an Indian gutter.

The gas impacts the brain cells' ability to use food and glucose, and ultimately resulting in the destruction of synapses, where the cells connect so information can be stored and memories made.

''So just think about this. If this protein is being chewed up, then neuron-to-neuron communication is disrupted,'' said Dr Nilkantha Sen, neuroscientist at the university's medical school. ''If it continues to happen in your brain or in my brain, our memory will be shut down.''

Sen is referencing damage to the protein PSD95, which is essential to the framework of the synapses that connect brain cells and gets modified by the gas hydrogen sulphide.

Loss of PSD95 already is implicated in dementia as well as depression, anxiety disorders, and addiction. IL-1 beta signalling in the brain plays a critical role in learning and memory however, the rapid accumulation that follows injury appears to have the opposite effect.

Two years ago, Sen was among the first to find that, at least in mice, stress, like an injury, upregulates expression of the IL-1 beta receptor on neurons, and that's where the trouble begins.

Essentially immediately, the activated receptor upregulates another transmitter, hydrogen sulphide, a gas better known for its ability to dilate blood vessels.

But as with IL-1 beta, at high levels, the gas seems more bent on cell destruction.

''It is maintained at a threshold level in every tissue of our body. But when it increases, it produces adverse reactions,'' Sen said.

In this case, hydrogen sulphide modifies GAPDH, an enzyme essential to the brain cell's ability to use its major food source, glucose.

The modified GAPDH then binds with Siah, a protein important to the body's ability to degrade improperly folded proteins.

In this situation, Siah binds to and degrades PSD95, a molecule essential to the scaffolding of the synapses. Sen and his colleagues note that Siah's attack on PSD95 may be considered a general mechanism for inflammation-associated synaptic and memory damage.

''It kills a very important protein for synaptic plasticity,'' Sen said.

''This is a completely novel mechanism,'' which Sen said he hopes will one day translate to a novel therapy for several neurodegenerative disorders as well as brain injury by targeting modified GAPDH.

The study was published in the journal Molecular Cell.





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