Summary: Using patient-derived adult stem cells, researchers found fish oil created an antidepressant response.
Source: University of Illinois
A study published in Molecular Psychiatry shows that patient-derived adult stem cells can be used to model major depressive disorder and test how a patient may respond to medication.
Using stem cells from adults with a clinical diagnosis of depression, the University of Illinois at Chicago researchers who conducted the study also found that fish oil, when tested in the model, created an antidepressant response.
UIC’s Mark Rasenick, principal investigator of the study, says that the research provides a number of novel findings that can help scientists better understand how the brain works and why some people respond to drug treatment for depression, while others experience limited benefits from antidepressant medication.
“It was also exciting to find scientific evidence that fish oil — an easy-to-get, natural product — may be an effective treatment for depression,” said Rasenick, UIC distinguished professor of physiology and biophysics and psychiatry at the College of Medicine.
Major depressive disorder, or depression, is the most common psychiatric disorder. Around one in six individuals will experience at least one depressive episode in their lifetime. However, antidepressant treatment fails in about one-third of patients.
In the study, the UIC researchers used skin cells from adults with depression that were converted into stem cells at Massachusetts General Hospital and then directed those stem cells to develop into nerve cells. The skin biopsies were taken from two types of patients: people who previously responded to antidepressant treatment and people who have previously been resistant to antidepressants.
When fish oil was tested, the models from treatment-sensitive and treatment-resistant patients both responded.
Rasenick says the response was similar to that seen from prescription antidepressants, but it was produced through a different mechanism.
“We saw that fish oil was acting, in part, on glial cells, not neurons,” said Rasenick, who is also a research career scientist at Jesse Brown VA Medical Center and president and chief scientific officer at Pax Neuroscience, a UIC startup company. “For many years, scientists have paid scant attention to glia — a type of brain cell that surrounds neurons — but there is increasing evidence that glia may play a role in depression. Our study suggests that glia may also be important for antidepressant action.
“Our study also showed that a stem cell model can be used to study response to treatment and that fish oil as a treatment, or companion to treatment, for depression warrants further investigation,” Rasenick said.
Co-authors on the study are Jiang-Zhou Yu of UIC and Jennifer Wang, Steven Sheridan and Roy Perlis of Massachusetts General Hospital.
Funding: This study was supported by grant awards from the National Institutes of Health (R01AT009169, R41MH113398) and a VA Merit Award (BX00149). Patient cell line collection and derivation were supported by funding from the NIH (P50MH106933, R01AT009144). The authors noted relevant financial disclosures.
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University of Illinois
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Jackie Carey – University of Illinois
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Original Research: Closed access
“N-3 polyunsaturated fatty acids promote astrocyte differentiation and neurotrophin production independent of cAMP in patient-derived neural stem cells” by Jiang-Zhou Yu, Jennifer Wang, Steven D. Sheridan, Roy H. Perlis & Mark M. Rasenick.
Molecular Psychiatry doi:10.1038/s41380-020-0786-5
Abstract
N-3 polyunsaturated fatty acids promote astrocyte differentiation and neurotrophin production independent of cAMP in patient-derived neural stem cells
Evidence from epidemiological and laboratory studies, as well as randomized placebo-controlled trials, suggests supplementation with n-3 polyunsaturated fatty acids (PUFAs) may be efficacious for treatment of major depressive disorder (MDD). The mechanisms underlying n-3 PUFAs potential therapeutic properties remain unknown. There are suggestions in the literature that glial hypofunction is associated with depressive symptoms and that antidepressants may normalize glial function. In this study, induced pluripotent stem cells (iPSC)-derived neuronal stem cell lines were generated from individuals with MDD. Astrocytes differentiated from patient-derived neuronal stem cells (iNSCs) were verified by GFAP. Cells were treated with eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) or stearic acid (SA). During astrocyte differentiation, we found that n-3 PUFAs increased GFAP expression and GFAP positive cell formation. BDNF and GDNF production were increased in the astrocytes derived from patients subsequent to n-3 PUFA treatment. Stearic Acid (SA) treatment did not have this effect. CREB activity (phosphorylated CREB) was also increased by DHA and EPA but not by SA. Furthermore, when these astrocytes were treated with n-3 PUFAs, the cAMP antagonist, RP-cAMPs did not block n-3 PUFA CREB activation. However, the CREB specific inhibitor (666-15) diminished BDNF and GDNF production induced by n-3 PUFA, suggesting CREB dependence. Together, these results suggested that n-3 PUFAs facilitate astrocyte differentiation, and may mimic effects of some antidepressants by increasing production of neurotrophic factors. The CREB-dependence and cAMP independence of this process suggests a manner in which n-3 PUFA could augment antidepressant effects. These data also suggest a role for astrocytes in both MDD and antidepressant action.
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