A University of Queensland research team is challenging how we think about the brain’s bioenergetics, overturning the field to show that saturated free fatty acids contribute to both energy and signalling that powers synaptic plasticity.
Synaptic plasticity is the brain's ability to strengthen, weaken, and reorganise connections between nerve cells, allowing us to learn, remember and adapt. It requires the rapid coordination of electrical activity, membrane remodelling, protein turnover, and energy production.
Fatty acids in memory formation
Queensland Brain Institute Professor Frederic Meunier said in earlier research the team revealed saturated fatty acid levels, especially myristic acid, unexpectedly surge in the brain during memory formation.
“Then we identified the mechanism, an enzyme called DDHD2, Phospholipase A1 (PLA1) isoform that interacts with another protein at the synapse called STXBP1, that generate saturated fatty acids such as myristic acid,” Professor Meunier said.
“We also discovered that myristic acid formed during learning, is in turn then used to chemically “tag” synaptic proteins, enabling the interactions required for the synapse to strengthen.”
A new perspective
Postdoctoral Research Fellow Dr Saber Abdelkader and his colleagues have brought this evidence together, highlighted a new role for fatty acids, and proposed critical avenues for further exploration.
“Our latest findings broaden the traditional view that the brain relies predominantly on glucose for energy,” Dr Abdelkader said.
“Our work shows that neurons can also use locally released saturated fatty acids as a complementary energy source when their energy demands increase, such as during learning.
“One can think of DDHD2 as molecular scissors that target certain lipids and release saturated fatty acids.
“These can then be used by mitochondria, the energy-producing structures inside cells, to generate ATP.”
ATP carries energy in a form that cells can use immediately. It powers many of the processes that allow nerve cells to communicate and change their connections as we learn.
“What makes this pathway particularly interesting is that myristic and palmitic acids appear to have a dual role,” he said.
“It can contribute to energy production, but it can also be used to chemically modify key synaptic proteins, helping proteins interact in ways that strengthen the connections between nerve cells.
“The dual function of the free fatty acids is currently fuelling many new studies in this rapidly evolving field which ultimately explain how neurons can support enhanced activity during the memory formation, sometimes over a lifetime.”
A rapidly evolving field
While the QBI research team has established the dual role of fatty acids in synaptic plasticity, many questions remain:
- Where fatty acids come from and how these supplies are replenished
- How neurons balance using fatty acids for energy, attaching them to proteins to regulate their function, and storing them
- How much energy fatty acids provide and when it is important
- Whether fatty acids move between brain cells
Perhaps most importantly, the researchers are considering the role of fatty acids in ageing and disease, asking whether disruptions to this metabolic flexibility contribute to impaired synaptic function.
This perspective was published in The EMBO Journal.
