Ketones boost brain function and guard against diabetes & Alzheimer’s

Researchers at the Del Monte Institute for Neuroscience at the University of Rochester have uncovered how ketones can help restore essential functions in the brain’s hippocampal network. Their findings add to growing evidence that ketones may alleviate neurological and cognitive deficits.

Aging naturally increases the brain’s resistance to insulin, disrupting neuronal communication and contributing to mood changes, cognitive decline, and, ultimately, neurodegeneration.

Nathan A. Smith, MS, PhD ('13), an associate professor of Neuroscience, led a team investigating how sudden insulin resistance affects brain function—an issue often triggered by trauma and potentially preceding chronic conditions like diabetes or Alzheimer’s disease.

"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 study’s principal investigator.

Researchers publishing in PNAS Nexus investigated the early stages of neuronal dysfunction, aiming to identify when neurons begin to falter and explore strategies to restore their function. Their findings offer potential insights into delaying neurodegenerative diseases such as Alzheimer’s.

Using a mouse model, the team focused on the hippocampus, a brain region critical for learning and memory. They found that acute insulin resistance disrupts multiple aspects of neuronal function, including synaptic activity, axonal conduction, network synchronization, synaptic plasticity, and action potential properties—key processes for neuron-to-neuron communication.

To counteract these impairments, the researchers administered D-βHb, a ketone the liver produces when burning fat instead of glucose for energy.

The treatment restored synaptic activity, enhanced axonal conduction, resynchronized neurons, and improved synaptic plasticity, suggesting a potential therapeutic approach for preserving brain function.

"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.

Note: Materials provided above by the The Brighter Side of News. Content may be edited for style and length.

Like these kind of feel good stories? Get the Brighter Side of News' newsletter.