Abnormal levels of stress hormones such as adrenaline and cortisol are associated with a variety of mental health disorders, including depression and post-traumatic stress disorder (PTSD). MIT researchers have now found a way to control the release of these hormones from the adrenal glands, using magnetic nanoparticles.
This approach can help scientists learn more about how hormone release affects mental health, and ultimately can offer new ways to treat hormone-related disorders, the researchers said.
“We are looking for ways we can study and ultimately treat stress disorders by modulating the function of peripheral organs, rather than doing something very invasive in the central nervous system,” said Polina Anikeeva, an MIT professor in the fields of science and engineering of materials and brain and cognitive science .
To achieve control over hormone release, Dekel Rosenfeld, an MIT-Technion postdoc in the Anikeeva group, has developed special magnetic nanoparticles that can be injected into the adrenal glands. When exposed to a weak magnetic field, the particles heat up a little, activating heat-responsive channels that trigger hormone release. This technique can be used to stimulate organs deep in the body with minimal invasion.
Anikeeva and Alik Widge, assistant professor of psychiatry at the University of Minnesota and former researchers at the MIT Picower Institute for Learning and Memory, are senior authors of the study. Rosenfeld is the lead author of the paper, which appears today in Progress of Science.
The Anikeeva Laboratory has previously designed several magnetic nano materials, including particles that can release drugs at the right time at certain locations in the body.
In the new study, the research team wanted to explore the idea of treating brain disorders by manipulating organs that are outside the central nervous system but affecting them through hormone release. One well-known example is the hypothalamic-pituitary-adrenal (HPA) axis, which regulates the stress response in mammals. Hormones secreted by the adrenal glands, including cortisol and adrenaline, play an important role in depression, stress, and anxiety.
“Some disorders that we consider neurological may be treatable from the periphery, if we can learn to modulate local circuits rather than return to global circuits in the central nervous system,” said Anikeeva, who is a member of the MIT Research Laboratory. Electronics and the McGovern Institute for Brain Research.
As a target to stimulate hormone release, the researchers cut the ion channels which control the flow of calcium to adrenal cells. These ion channels can be activated by various stimuli, including heat. When calcium flows through open channels into adrenal cells, cells start pumping hormones. “If we want to modulate the release of these hormones, we must be able to modulate the entry of calcium into adrenal cells,” Rosenfeld said.
Unlike previous studies in the Anikeeva group, in this study magnetothermal stimulation was applied to modulate cell function without artificially introducing any genes.
To stimulate these heat-sensitive channels, which naturally occur in adrenal cells, the researchers designed nanoparticles made of magnetite, a type of iron oxide that forms tiny magnetic crystals about 1/5000 the thickness of human hair. In mice, they found these particles could be injected directly into the adrenal gland and remained there for at least six months. When mice are exposed to a weak magnetic field – around 50 militesla, 100 times weaker than the field used for magnetic resonance imaging (MRI) – the particles heat up around 6 degrees Celsius, enough to trigger calcium channels to open without damaging the surrounding tissue.
The heat-sensitive channels they target, known as TRPV1, are found in many sensory neurons throughout the body, including pain receptors. The TRPV1 channel can be activated by capsaicin, an organic compound that makes chili heat, and temperature. They are found in all mammal species, and belong to the family of many other channels that are also heat sensitive.
This stimulation triggers an increase in hormones – doubling cortisol production and increasing noradrenaline by about 25 percent. That causes a measurable increase in the animal’s heart rate.
Treat stress and pain
Researchers now plan to use this approach to study how hormone release affects PTSD and other disorders, and they say that in the end it can be adjusted to treat the disorder. This method will offer a far less invasive alternative to potential treatments that involve the implantation of medical devices to stimulate the release of hormones electrically, which are not feasible in organs such as the soft and highly vascularized adrenal glands, the researchers said.
Another area where this strategy can be promising is in the treatment of pain, because heat-sensitive ion channels are often found in pain receptors.
“Being able to modulate pain receptors with this technique will potentially allow us to study pain, control pain, and have several clinical applications in the future, which are expected to offer alternatives to drugs or implants for chronic pain,” Anikeeva said. With further investigation about the presence of TRPV1 in other organs, this technique has the potential to be extended to other peripheral organs such as the digestive system and pancreas.
Reprinted by permission of MIT. Photo: MIT engineers have developed magnetic nanoparticles (displayed in a white box) that can stimulate the adrenal glands to produce stress hormones such as adrenaline and cortisol. Credit: Researchers / MIT