Rochester, NY – As individuals age, their brain naturally becomes more insulin resistant, impacting neuron communication and potentially leading to cognitive decline and neurodegeneration. A recent study conducted by researchers at the University of Rochester delved into the effects of acute insulin resistance on neuronal function before symptoms of chronic conditions like Alzheimer’s disease emerge. Utilizing mouse models, the researchers discovered that ketones could potentially restore impaired synaptic activity, axonal conduction, and network synchronization, offering a glimpse into potential ketone-based therapies for neurodegenerative diseases.
The study, led by Nathan A. Smith, MS, PhD, an associate professor of Neuroscience, aimed to examine the mechanisms in the brain that break down when insulin resistance occurs suddenly, such as in cases of trauma, before manifesting into chronic conditions like diabetes or Alzheimer’s. The researchers focused on the hippocampus, a region of the brain crucial for learning and memory. They found that acute insulin resistance could impair several aspects of neuronal function, including synaptic activity, axonal conduction, network synchronization, synaptic plasticity, and action potential properties – all vital processes for facilitating communication within neurons.
By administering D-βHb, a form of ketones released by the liver during fat burning, the researchers observed a rescue of synaptic activity previously impacted by acute insulin resistance. Additionally, they noted increased conduction in axons, resynchronization of neurons, and improved synaptic plasticity. According to Smith, this research opens up possibilities for developing ketone-based therapies targeting specific neuronal dysfunctions in conditions involving insulin resistance and hypoglycemia, such as diabetes and Alzheimer’s disease.
The implications of this study extend beyond simply understanding the effects of insulin resistance on neuronal function; they also offer insights into potential preventive measures for devastating diseases like Alzheimer’s. Smith emphasized the importance of identifying the early stages of impaired neuronal function, as once the function is lost, recovery becomes nearly impossible. The research, published in the journal PNAS Nexus, brings scientists closer to understanding how to rescue impaired neurons and potentially delay or prevent the onset of neurodegenerative diseases.
Collaborating with researchers from institutions like Stony Brook University, Harvard Medical School, and Memorial Sloan Kettering Cancer Center, the team at the University of Rochester received support for their research from organizations like the National Institutes of Health, the National Science Foundation, and the Department of Defense. As they delve further into the role of astrocytes and other glial cells in acute insulin resistance, the researchers aim to uncover more insights that could lead to innovative therapies for conditions involving insulin resistance.