Abnormal levels of stress hormones such as adrenaline and cortisol are
linked to a variety of mental health disorders, including depression and
posttraumatic stress disorder (PTSD). MIT researchers have now devised a way to
remotely control the release of these hormones from the adrenal gland, using
magnetic nanoparticles.
This approach
could help scientists to learn more about how hormone release influences mental
health, and could eventually offer a new way to treat hormone-linked disorders,
the researchers say.
“We’re looking
how can we study and eventually treat stress disorders by modulating peripheral
organ function, rather than doing something highly invasive in the central
nervous system,” says Polina Anikeeva, an MIT professor of materials science
and engineering and of brain and cognitive sciences.
To achieve
control over hormone release, Dekel Rosenfeld, an MIT-Technion postdoc in
Anikeeva’s group, has developed specialized magnetic nanoparticles that can be injected
into the adrenal gland. When exposed to a weak magnetic field, the particles
heat up slightly, activating heat-responsive channels that trigger hormone
release. This technique can be used to stimulate an organ deep in the body with
minimal invasiveness.
Anikeeva and Alik Widge, an assistant professor of psychiatry at the
University of Minnesota and a former research fellow at MIT’s Picower Institute
for Learning and Memory, are the senior authors of the study. Rosenfeld is the
lead author of the paper, which appears today in Science Advances.
Controlling hormones
Anikeeva’s lab
has previously devised several novel magnetic nanomaterials, including
particles that can release drugs at precise times in specific locations in the
body.
In the new
study, the research team wanted to explore the idea of treating disorders of
the brain by manipulating organs that are outside the central nervous system
but influence it through hormone release. One well-known example is the
hypothalamic-pituitary-adrenal (HPA) axis, which regulates stress response in
mammals. Hormones secreted by the adrenal gland, including cortisol and
adrenaline, play important roles in depression, stress, and anxiety.
“Some disorders
that we consider neurological may be treatable from the periphery, if we can
learn to modulate those local circuits rather than going back to the global
circuits in the central nervous system,” says Anikeeva, who is a member of
MIT’s Research Laboratory of Electronics and McGovern Institute for Brain
Research.
As a target to
stimulate hormone release, the researchers decided on ion channels that control
the flow of calcium into adrenal cells. Those ion channels can be activated by
a variety of stimuli, including heat. When calcium flows through the open
channels into adrenal cells, the cells begin pumping out hormones. “If we want
to modulate the release of those hormones, we need to be able to essentially
modulate the influx of calcium into adrenal cells,” Rosenfeld says.
Unlike previous
research in Anikeeva’s group, in this study magnetothermal stimulation was
applied to modulate the function of cells 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 a human hair. In
rats, they found these particles could be injected directly into the adrenal
glands and remain there for at least six months. When the rats were exposed to
a weak magnetic field — about 50 millitesla, 100 times weaker than the fields
used for magnetic resonance imaging (MRI) — the particles heated up by about 6
degrees Celsius, enough to trigger the calcium channels to open without damaging
any surrounding tissue.
The
heat-sensitive channel that they targeted, known as TRPV1, is found in many
sensory neurons throughout the body, including pain receptors. TRPV1 channels
can be activated by capsaicin, the organic compound that gives chili peppers
their heat, as well as by temperature. They are found across mammalian species,
and belong to a family of many other channels that are also sensitive to heat.
This stimulation
triggered a hormone rush — doubling cortisol production and boosting noradrenaline
by about 25 percent. That led to a measurable increase in the animals’ heart
rates.
Treating stress and pain
The researchers
now plan to use this approach to study how hormone release affects PTSD and
other disorders, and they say that eventually it could be adapted for treating
such disorders. This method would offer a much less invasive alternative to
potential treatments that involve implanting a medical device to electrically
stimulate hormone release, which is not feasible in organs such as the adrenal
glands that are soft and highly vascularized, the researchers say.
Another area
where this strategy could hold promise 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 potentially will allow us to study
pain, control pain, and have some clinical applications in the future, which
hopefully may offer an alternative to medications or implants for chronic
pain,” Anikeeva says. With further investigation of the existence of TRPV1 in
other organs, the technique can potentially be extended to other peripheral organs
such as the digestive system and the pancreas.
Journal article: https://advances.sciencemag.org/content/6/15/eaaz3734
No comments:
Post a Comment