A team of researchers from the Johns Hopkins Bloomberg School of Public Health has detected the damaging side effects of antidepressants on the human brain through the use of lab-grown “mini-brains” derived from stem cells. Mini-brains are the miniature models of the human brain, derived using stem cells and nearly invisible to the naked eye, whose cellular mechanisms appear similar to that of the developing human brain. The findings of the study have been published in the scientific journal Frontiers of Cellular Neuroscience.
The team used —mini-brains to demonstrate that the antidepressant paroxetine — also known as Paxil or Seroxat — prevents the growth of brain synapses, which are the points where neurons connect. This ultimately leads to a significant decrease in a crucial support-cell population. Paxil is an antidepressant that usually comes with a warning against use during the early trimester, primarily due to the risk of heart and lung defects. Few studies have also indicated that this drug increases the risk of autism.
Paxil and other such antidepressants fall under the category of SSRIs or selective serotonin reuptake inhibitors and are among the world’s most commonly recommended antidepressants. The new findings are probably going to raise concerns about the side-effects of the drug on the developing brain. The researchers state that the lab-grown brains, also referred to as BrainSpheres, are an excellent substitute for conventional animal testing. Besides, they can reveal chemicals that are harmful to the developing brain.
Professor Thomas Hartung, Chair of the Department of Environmental Health and Engineering and Director of the Center for Alternatives to Animal Testing at the Bloomberg School, who also co-authored the study, said: “There’s a rising concern that we have a plethora neurodevelopmental disorders, such as autism, and that these might be caused because of exposure to antidepressants and similar drugs or other chemicals. In any case, since conventional animal testing has not remained so cheap, we haven’t been able to look into this question properly.”
The team grew mini-brains in the laboratory to model early brain development. The tiny clusters of brain tissue are made by extracting cells from humans and transforming them into stem cells. These are then biochemically nudged to develop into young brain cells. The lab-grown mini-brains form a brain-like organization over a few months. Since they are produced at large in the lab, they are inexpensive to work with than animals.
The team of researchers exposed the mini-brains to two different doses of Paxil for eight weeks as the clusters of tissue developed. Both the doses were within the therapeutic range for blood levels of the antidepressant in humans. Furthermore, the team used two different sets of mini-brains in the experiments, each derived from a different stem cell.
The researchers found that while Paxil did not seem to have any particular destructive effect on neurons, at the higher concentration, it did lower the levels of a protein known as synaptophysin, a market of synapses, by up to 80%. The drug also lowered two levels of other synapse-related components as well. Likewise, the researchers noted that the drug reduced the normal outgrowth of neurites — structures that eventually develop into the branches of mature neurons. The team also found that mini-brains exposed to paroxetine developed up to 75% fewer oligodendrocytes — the support cells that are important for the upper “wiring” of the brain — compared to control groups. The findings suggest that the antidepressant might affect the healthy formation of neurons, thereby leading to neurodevelopmental disorders such as autism.