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Measuring Brain Chemistry

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Anne Andrews

Anne Andrews
Credit: From the American Chemical Society’s “Personal Stories of Discovery”

Serotonin is one of the chemical messengers that nerve cells in the brain use to communicate. Modifying serotonin levels is one way that antidepressant and anti-anxiety medications are thought to work and help people feel better. But the precise nature of serotonin’s role in the brain is largely unknown.

That’s why Anne Andrews set out in the mid-1990s as a fellow at NIH’s National Institute of Mental Health to explore changes in serotonin levels in the brains of anxious mice. But she quickly realized it wasn’t possible. The tools available for measuring serotonin—and most other neurochemicals in the brain—couldn’t offer the needed precision to conduct her studies.

Instead of giving up, Andrews did something about it. In the late 1990s, she began formulating an idea for a neural probe to make direct and precise measurements of brain chemistry. Her progress was initially slow, partly because the probe she envisioned was technologically ahead of its time. Now at the University of California, Los Angeles (UCLA) more than 15 years later, she’s nearly there. Buoyed by recent scientific breakthroughs, the right team to get the job done, and the support of a 2017 NIH Director’s Transformative Research Award, Andrews expects to have the first fully functional devices ready within the next two years.

Neurotransmitters are often present in extremely low concentrations in the spaces outside of neurons, where communication takes place. That has made designing a neural probe sensitive enough to detect them with the needed specificity a huge challenge. Andrews’ team—including Milan Stojanović, Columbia University, New York City, along with UCLA’s Paul Weiss, Harold Monbouquette, and Yang Yang—found a solution in molecules known as aptamers. They are single stranded nucleic acids that are selected for their unique ability to bind a chemical structure of interest.

Andrews’ team now has aptamers that recognize a number of essential nerve messengers, including serotonin and dopamine, with many more in development. Andrews reports that these aptamers are selective and sensitive enough to differentiate between chemicals that are very similar in structure.

One recent breakthrough was coupling these aptamers to semiconductor materials in field-effect transistors, the same basic elements in today’s common electronic devices such as cell phones and laptops. Because aptamers are small and electrically charged, Andrews found that when aptamers bind to neurotransmitters, even in brain fluid that contains many ions, electronic signals could be detected at the transistors.

The next challenge is to couple aptamer-transistor sensors with small implantable devices with the goal to achieve fully electronic neurochemical sensors small enough for use in tiny mouse brains. Andrews is seeking to develop a device that’s about the width of a human hair. If all goes well, the length of the probes and the types of individual sensors will also be fully customizable to target any area of the brain and any neurotransmitter.

While Andrews is designing the device primarily for laboratory use, she suspects her new tool might ultimately have medical applications. For example, she envisions doctors using the sensors alongside neurostimulators implanted into the brain for treating psychiatric illnesses, including severe depression and post-traumatic stress disorder. Doctors today struggle to determine where best to place such devices in each patient’s brain for the maximum benefit. There’s also limited information about how deep brain stimulation works to influence brain chemistry in patients. Andrews’ neurochemical sensors have potential to provide insight on both counts.

Ultimately, the sensors will be readily adaptable and available for measuring any neurotransmitter for essentially any research application. As remarkable as that is, Andrews still doesn’t consider herself a tool developer at heart. What she’s most looking forward to is working with her mice and capturing those measures of brain serotonin with the precision that she first sought all those years ago—and to learn what serotonin levels reveal about the brain chemistry behind anxiety.

Links:

Anne Andrews Lab (UCLA)

Anne M. Andrews’ Personal Story of Discovery (American Chemical Society)

Milan Stojanovic (Columbia University, New York City)

Paul Weiss (UCLA)

Harold Monbouquette (UCLA)

Yang Yang (UCLA)

Andrews Project Information (NIH RePORTER)

NIH Director’s Transformative Research Program (Common Fund)

NIH Support: National Institute on Drug Abuse; Common Fund

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6 Comments

  • J.S. says:

    Humbly, can I invite you to NeuroFutures 2018?

  • Barbara says:

    The serotonin / *Chemical Imbalance* theory of depression was disavowed by psychiatry (APA) YEARS ago and attributed to pharma marketing. Please stop beating this dead horse.

  • Connie M. says:

    How wonderful. I have seen first hand how anxiety can effect and change how a person tries to live in a world with their fears.

  • Cindy B. says:

    my mother has had (parkinson’s) for about 20 years. they put her on dopamine and serotonin about 10 years into it, at first it helped her a great deal maybe the first 5 years but then even after increasing it
    it did not seem to help as much like she stopped responding to it I don’t know if that could be and because DR’S don’t care any more and are not made to up hold there oath people will just go by the way side so sad how the world has become so heartless and cold to people I know because back in 2011 my husband was in a 3 car accident and was left with severe spinal damage and head trauma
    and in 5 years I have seen more crap then I cared to see as far as the caring goes in hospitals and DR’S. and ins. makes know differance my husband was covered front to back and side to side and the way they treated him and me when they were discharging him or transporting to a rehab. was unreal.
    I thought I was going to go into shock I was on the phone with the CEO of his company when decided to transport him, and they did this transporting so wrong and they knew it but because I had ask so many questions and called them on so many things that they had done wrong the transported him
    (BY VAN) and while I was on the phone on another floor they did not wait so I could follow behind them, And when i had arrived and asking for the charge nurse as she was walking up to me I knew something was wrong and there was there were know ORDERS attached or anything she told me she had never had a person arrive that way and this was the part that pissed me off they transported him
    without oxygen my god i was appalled, At that time i had decided the world had went to hell because know one makes anyone held accountable. thank you for letting me read and to tell my story.

  • John Evans says:

    Interesting article. The research with serotonin and how it affects brain chemistry is truly a wonderful idea. In all the years I worked in Law Enforcement, I have seen first hand how the illegal drug academic has affected our society. In my past experience working for large county police departments I had the job of charging individuals for violating our American Drug Laws. I would communicate with these folks after taking them into custody. The main reason they used these type of drugs was to make attempts to self-medicate.
    In my communication with these folks they really had no interest in the use of the drug itself. These folks suffered from multiple anxiety issues ( Schizophrenia, Bi-polar personality etc ) and they only wanted to be normal and fit into society. The use of these drugs was to change their Serotonin levels in the brain so if even for an instant they could feel what society sees as normal. I just think the research in this field is a wonderful idea.

  • Charles Gurd says:

    Very exciting work and very much needed to help develop tools to treat neurological and mental health disorders.

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