The critical role of saturated fats in memory consolidation

University of Queensland researchers have uncovered the critical role that saturated fats play in the brain's memory consolidation process.

Exploring Lipids and Memory in the Fattest Organ in Humans
Dr Isaac Akefe and Professor Frederic Meunier in a QBI laboratory. Image Credit: The University of Queensland

The Queensland Brain Institute at the University of Queensland's Dr Isaac Akefe has discovered the genes and molecular mechanisms behind the formation of memory. Uncovering this process may be vital in future research aiming to dicover treatment options for neurodegenerative diseases.

We have shown previously that levels of saturated fatty acids increase in the brain during neuronal communication, but we didn’t know what was causing these changes, and Now for the first time, we have identified alterations in the brain’s fatty acid landscape when the neurons encode a memory.”

Dr Isaac Akefe, Queensland Brain Institute, The University of Queensland

Isaac Akefe said, “An enzyme called Phospholipase A1 (PLA1) interacts with another protein at the synapse called STXBP1 to form saturated fatty acids.”

The brain is the fattest organ in the body, containing 60% of its weight in lipids, or fatty substances. The building blocks of phospholipids, a class of lipids, are fatty acids.

Research conducted in the lab of Professor Frederic Meunier has demonstrated that STXBP1 regulates the targeting of the PLA1 enzyme, controlling communication at the brain's synapses and coordinating the release of fatty acids.

Human mutations in the PLA1 and the STXBP1 genes reduce free fatty acid levels and promote neurological disorders, and to determine the importance of free fatty acids in memory formation, we used mouse models where the PLA1 gene is removed.”

Frederic Meunier, Professor, The University of Queensland

Meunier said, “We tracked the onset and progression of neurological and cognitive decline throughout their lives, and saw that even before their memories became impaired, their saturated free fatty acid levels were significantly lower than control mice, this indicates that this PLA1 enzyme, and the fatty acids it releases, play a key role in memory acquisition.”

The findings have significant ramifications for our comprehension of memory formation.

Our findings indicate that manipulating this memory acquisition pathway has exciting potential as a treatment for neurodegenerative diseases, such as Alzheimer’s.”

Frederic Meunier, Professor, The University of Queensland

PhD candidates Saber Abd Elkader from the Australian Institute for Bioengineering and Nanotechnology and Benjamin Matthews from the Queensland Brain Institute contributed to the study.

The University of New South Wales, the University of Strasbourg, the University of Bordeaux, The Scripps Research Institute, and the Baylor College of Medicine participated in the research.

Source:
Journal reference:

Akefe, I. O., et.al., (2024). The DDHD2-STXBP1 interaction mediates long-term memory via generation of saturated free fatty acids. EMBO. doi.org/10.1038/s44318-024-00030-7

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