The UK-based research team writes in Molecular Psychiatry, researching mechanisms in the body that omega-3 fatty acids could help reduce inflammation or depression, providing a springboard for more targeted research.
“We have known for some time that omega-3 PUFAs can produce antidepressant and anti-inflammatory effects, but without further understanding how this happens in the human brain, treatments have been difficult to develop,” says Dr. Alessandra Borsini, lead study author and Senior Postdoctoral Neuroscientist at King’s College London.
“Our study helped shed light on the molecular mechanisms involved in this relationship that may aid the development of potential new treatments for depression using omega-3 polyunsaturated fatty acids (PUFA).”
Collaboration between the University of Manchester Manchester
The study, in which colleagues from the University of Manchester were involved, focused on omega-3 fatty acid metabolites called lipid mediators and their ability to protect the brain from the harmful effects of inflammation.
Using a validated in vitro model of human cells using hippocampal cells, the team first treated these cells with the omega-3 fatty acids EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid).
The cells were then exposed to chemical messengers that are involved in inflammation, preventing increased cell death and reducing the production of new neurons.
Further work found that these effects were monitored by lipid mediators produced by EPA and DHA called hydroxyeicosapentaenoic acid (HEPE), hydroxydocosahexaenoic acid (HDHA), epoxyeicosatetraenoic acid (EpETE), and epoxydocosapentaenoic acid (EpDPA).
The team then presented an enzyme inhibitor that increases the availability of EpETE and EpDPA, which could form the basis for a therapy to combat depression.
“The lipid mediators identified in our research are broken down relatively quickly in the body and may therefore only be available for a relatively short time,” explains Professor Anna Nicolaou, Professor of Biological Chemistry at the Faculty of Medicine and Human Sciences. Manchester University.
“By testing the effect of inhibitors of the enzymes involved in the metabolism of omega-3 PUFAs, we have shown that we can greatly improve their duration in the body and ultimately increase their effectiveness.
“This is very important in the development of new treatments and means that patients, along with these enzyme inhibitors, could receive higher doses of EPA and DHA to increase the amount of these important compounds in their blood over time.”
“Internationally respected team”
The reaction of the experts to the results has been generally positive. Dr. Eric Ruhé, psychiatrist and epidemiologist at Radboud University Medical Center in the Netherlands, said: “If the next steps are taken and are positive, this finding could be an important contributor to the pre-stratification of depressed patients, targeted mechanistically based treatments instead of the current trial and error Change approach. “
Dr. Michael Bloomfield, Excellence Fellow, Head of Translational Psychiatry Research Group and Counseling Psychiatrist at UCL, added, “This is fascinating research being carried out by an internationally renowned team of scientists.
“This new study sheds light on potential mechanisms underlying the response to omega oils. This is important as understanding these mechanisms could lead to new treatment goals and explain why some people seem to get better with omega oils and others don’t.
“Still, more research is needed on omega oils and their potential mechanisms of action.”
More research needed
The article’s senior author, Professor Carmine Pariante, National Institute of Health Research (NIHR), Maudsley BRC Affective Disorders Interface with Medicine Theme Lead, said, “By identifying and measuring the exact lipid mediators involved, identifying the enzyme that causes their effects By searching for the same lipid mediators in depressed patients treated with omega-3 PUFA and improving symptoms, we have provided important information to help shape clinical trials for future therapeutic approaches with omega-3 fatty acids.
“It is important to emphasize that our research has not shown that simply increasing the omega-3s in our diet or taking supplements can reduce inflammation or depression.
“The mechanisms behind the associations between depression and omega-3 PUFA are complex and require further research and clinical studies to fully understand how they work and inform future therapeutic approaches.”
Source: Nature Molecular Psychiatry
Published online: doi.org/10.1038/s41380-021-01160-8
“Polyunsaturated omega-3 fatty acids protect against inflammation through the production of LOX and CYP450 lipid mediators: relevance for severe depression and for human hippocampal neurogenesis.”
Authors: Borsini, A et al.