Ketones can improve brain function and protect against diabetes and alzheimers

Researchers at the Del Monte Institute for Neuroscience at the University of Rochester have discovered how ketones can restore critical functions in the brain's hippocampal network. These findings build on previous research suggesting that ketones can alleviate neurological and cognitive deficits.

As we age, our brains naturally become more resistant to insulin. This resistance disrupts communication between neurons, leading to symptoms such as mood changes, cognitive decline, and eventually neurodegeneration.

Nathan A. Smith, MS, PhD ('13), an associate professor of Neuroscience, along with his team, investigated the brain mechanisms that deteriorate due to sudden insulin resistance, often seen in trauma, but before these symptoms progress to chronic conditions like diabetes or Alzheimer's.

"Once neuronal function is lost, there is no recovering the connection, so we need to identify when the function first becomes impaired," said Smith, the principal investigator of this research, which was published in the journal PNAS Nexus. "This study accomplishes that by bringing us closer to understanding how to rescue the function of impaired neurons and prevent or delay devastating diseases like Alzheimer's."

The researchers used mice as a model system, focusing on the hippocampus, a region of the brain essential for learning and memory. They discovered that acute insulin resistance impairs several aspects of neuronal function, including synaptic activity, axonal conduction, network synchronization, synaptic plasticity, and action potential properties—processes vital for communication flow in and out of neurons.

To counteract these impairments, the researchers administered D-βHb, a type of ketone produced by the liver when the body burns fat instead of glucose for energy.

They found that the synaptic activity previously affected by acute insulin resistance was restored. Additionally, conduction in axons increased, neurons were resynchronized, and synaptic plasticity improved.

"This research has implications for developing ketone-based therapies targeting specific neuronal dysfunctions in conditions involving insulin resistance or hypoglycemia, such as diabetes or Alzheimer's disease," Smith explained. "We are now looking to understand the role that astrocytes and other glia cells play in acute insulin resistance."

The significance of this research lies in its potential to pave the way for new treatments for neurodegenerative diseases. As the global population ages, the prevalence of conditions like Alzheimer's disease is expected to rise. Current treatments only address symptoms and do not halt or reverse the progression of the disease. However, the discovery of ketones' ability to restore neuronal functions offers a promising avenue for future therapies.

By targeting the early stages of neuronal impairment, these therapies could prevent or delay the onset of severe cognitive decline and neurodegeneration. This research also underscores the importance of understanding the metabolic processes in the brain and how they can be manipulated to promote brain health.

Smith and his team are now focused on further exploring the role of astrocytes and other glial cells in the context of insulin resistance. Astrocytes, a type of glial cell, play a critical role in supporting neuronal function and maintaining the brain's homeostasis. Understanding how these cells respond to insulin resistance could provide deeper insights into the mechanisms underlying neurodegenerative diseases and lead to more targeted interventions.

The potential for ketone-based therapies extends beyond Alzheimer's disease and diabetes. Other conditions characterized by impaired neuronal communication, such as traumatic brain injury and epilepsy, could also benefit from these findings. By enhancing our understanding of how ketones interact with the brain's metabolic processes, researchers can develop more effective treatments for a range of neurological disorders.

As the scientific community continues to explore the intricate relationship between brain metabolism and cognitive health, findings like these bring us one step closer to combating the devastating effects of aging on the brain.

Additional authors include Bartosz Kula, PhD, of the Del Monte Institute for Neuroscience at the University of Rochester, Botond Antal and Lilianne Mujica-Parodi, PhD, of Stony Brook University and Harvard Medical School, Corey Weistuch, PhD, of Memorial Sloan Kettering Cancer Center, Florian Gackiere, PhD, Alexander Barre, PhD, and Jeffrey Hubbard, PhD, of Neuroservices Alliance, and Maria Kukley, PhD, of Achucarro Basque Center for Neuroscience and Basque Foundation for Science. This research was supported by The National Institutes of Health, the National Science Foundation, and the Department of Defense.

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