Cardiovascular Disease Associated with Stress in Neurons

Oxidative stress, defined as elevated amounts of unstable chemicals known as reactive oxygen species, has been linked to dementia and cardiovascular disease. However, until recently, no causal association between oxidative stress and disease states could be shown.

A new study employed “chemogenetics” to activate a recombinant yeast protein expressed in mouse tissues, allowing researchers to regulate oxidative stress levels in living mice. Researchers from Brigham and Women’s Hospital, Harvard Medical School, and the Novartis Institutes for Biomedical Research used chemogenetic techniques to deliver oxidative stress into blood arteries and neurons in a new transgenic mouse model.

The researchers intended to use this new transgenic mouse model to find routes via which oxidative stress could cause blood vessel malfunction and contribute to illnesses such as hypertension and cardiovascular disease. They were astonished, however, to discover that these mice swiftly acquired significant ataxia, which is characterized by an inability to walk.

Further investigation revealed that specific sets of sensory neurons in peripheral nerve cells were degenerated due to oxidative stress caused by the transgene. When the researchers examined the hearts of the animals, they discovered that the heart muscle had acquired cardiac hypertrophy.

Friedreich’s ataxia (FA), a progressive neurological illness that is the most frequent form of hereditary ataxia observed in patients, is related with this combination of sensory neuron degeneration and heart enlargement. Researchers also identified particular inflammatory cell types implicated in these reactions, providing a more detailed picture of how FA induces heart hypertrophy.

“Our team followed up on an unexpected phenotype that we uncovered in a new transgenic mouse line and found surprising new connections between peripheral nerves and the heart,” said Thomas M. Michel, MD, Ph.D. of the Brigham Division of Cardiovascular Medicine. “Our findings may help us understand the cardiac remodeling seen in the hearts of patients with neurodegenerative diseases.”

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