Astrocytes from dysfunctional patients with bipolar disorder

Brain cells, called astrocytes, derived from induced pluripotent stem cells in patients with bipolar disorder do not provide optimal support for neural activity.In a paper published in the journal on March 4th Stem cell reportResearchers have shown that this dysfunction may be due to an pro-inflammatory molecule called interleukin-6 (IL-6) secreted by astrocytes. The results, which require further investigation, underscore the potential role of stellate-mediated inflammatory signaling in mental illness.

“Our findings suggest that IL-6 may contribute to defects associated with bipolar disorder and open new avenues for clinical intervention,” said the Salk Institute for Biological Studies. Principal Research Author Fred Gage said.

About 1-3% of individuals suffer from bipolar disorder. Bipolar disorder is characterized by the recurrence of a variety of mood states, including: High energy And an uplifting feeling for low energy and depression episodes known as mania. Some evidence suggests an association between imbalanced inflammatory signaling and bipolar disorder. For example, these patients show signs of chronic inflammation and are at an increased prevalence of inflammation-related symptoms such as cardiovascular disease, diabetes, and metabolic syndrome. In addition, they have high concentrations of circulating pro-inflammatory cytokines such as IL-1β and IL-6, especially during manic episodes.

“Mild inflammation is beneficial to many medicinal processes, but overproduction of IL-6 can exacerbate the symptoms of bipolar disorder and can be an important therapeutic target,” he said. Maria Carolina Marchetto, co-principal research author of the Salk Institute for Biological Studies, said. Faculty of Anthropology at the University of California, San Diego and the University of California, San Diego.

Astrocytes are known to be involved in the inflammatory cascade in the brain. These cells are activated by IL-1β and other pro-inflammatory cytokines, which in turn secrete cytokines involved in the process of neuroinflammation. “With a better understanding of the role of neuroinflammation in psychiatric disorders, I wondered if changes in inflammatory signaling in astrocytes are associated with bipolar disorder,” said co-principal research author. Renata Santos and Institute of Psychiatry and Neuroscience of Paris in Salk.

Researchers have previously developed a method for rapidly generating inflammatory-responsive astrocytes from human induced pluripotent stem cells (iPSCs). A new study compared signs of inflammation of iPSC-derived astrocytes generated from 6 patients with bipolar disorder and 4 healthy individuals.

Patient’s reaction to astrocytes to professionalsInflammatory cytokines We have revealed a unique transcription pattern characterized by higher expression of the IL-6 gene. As a result, these cells secreted more IL-6, adversely affecting the activity of co-cultured neurons.Exposure of astrocytes to the medium was sufficient to reduce Nervous activity, And this effect was partially blocked by IL-6 inactivated antibody. In addition, blood levels of IL-6 were higher in patients compared to healthy individuals.

“These results show that factors secreted by astrocytes play a role in the regulation of neural activity, and in bipolar disorder, IL-6 at least partially affects the neural activity of pro-inflammatory astrocytes. It suggests that it was mediated, “said the lead author, Krishna. Baddalia at the Salk Institute for Biological Research.

In the future, researchers plan to further investigate the effects of IL-6 on neural activity. In the meantime, the findings should be interpreted with caution.Experiments may not mimic the associated chronic inflammatory conditions Bipolar disorder, And the culture system did not contain many cell types involved in potentially associated immune responses. In addition, iPSC-derived astrocytes are relatively immature compared to the brains of patients with bipolar disorder and lack reliable biomarkers to accurately identify the exact age of development.

“At this point, it’s still difficult to extrapolate the results directly to the patient,” says Gage. “Despite these limitations, our findings reveal aspects of the under-studied role of astrocytes in psychiatric neuroinflammation. Disability.. ”