In "Ultrafast Detection and Quantification of Brain Signaling Molecules with Carbon Fiber Microelectrodes," published in the Oct. 2 issue of Analytical Chemistry, Parastoo Hashemi, Ph.D., assistant professor of chemistry in the College of Liberal Arts and Sciences, examines the use of carbon fiber microelectrodes (CFM) in neurochemical measurements, with an emphasis on the most recent findings and technological advances.
The field is more critical than ever, she said, with the increasing number of diagnoses of Alzheimer's and Parkinson's diseases, which remain largely untreatable, and with a surge in reports of mood disorders and substance abuse.
The brain comprises many different types of cells with different roles, and all of those cells communicate through synapses, where chemicals interact.
"For us to really understand the brain, we have to understand its chemistry, and to understand the chemistry, we have to understand how these chemicals move around in the synapse," Hashemi said. "We need to know what different molecules are there so we can assign specific roles to specific molecules."
CFMs have proven a good tool for analyzing brain chemicals, which Hashemi said requires adhering to four criteria: size, speed, selectivity and sensitivity — what her group calls the four S's.
Selectivity is needed to distinguished between types of chemicals; sensitivity because chemicals often are present in low levels. Speed is important because chemicals fluctuate dynamically — as in processing of conversation, for example — and small size is necessary to fit in gaps between areas of tissue the electrode is intended to sample.
CFMs now can be made very small — 1/100 the thickness of a human hair — and are uniquely biocompatible. Because other molecules don't stick to CFMs, Hashemi said, the fibers induce little inflammation or rejection response from tissue.
Their small size enables CFMs to be combined in microarrays to measure reactions in multiple synapses simultaneously, giving researchers greater insight into how various parts of the brain work together. Amperometry is one technique for using CFMs, and works well in a highly controlled system, she said.
"If you have a bunch of cells and you know what's in them already, you can put electrodes right next to a cell and essentially hold it at constant voltage value and oxidize everything that comes out," Hashemi said. "If you know what's in there, you can get really fast, really sensitive responses."
Amperometry enables researchers to expose cells to materials in consumer goods, such as bisphenol A, commonly known as BPA, to see how cell function is impaired, she said, adding, "It's a very effective, neat preparation."
Fast-scan cyclic voltammetry (FSCV) is another analysis technique using CFMs to identify specific reactions based on voltages at which molecules give up electrons (a process known as oxidation) or receive them (reduction). Hashemi uses it in her laboratory to scan quickly between certain potential limits of such electron transfers, because voltage is unique to each molecule. Though a little slower than amperometry, she said, FSCV fulfills all four S's.
"Whether it's 100 scans a second or 10 scans a second, one of the biggest challenges has been making hardware that can cope with something so fast as measuring the currents that we need, but that has been done," Hashemi said. "Because of that, FSCV can tell you not only how much of chemical there was, but whether it was dopamine, serotonin or something else. Each chemical gives a unique signature that is quite different in different species."
Hashemi's team has honed in on serotonin, a molecule involved in depression and anxiety that often is present in very low concentrations or in combination with other chemicals. While some drug treatments for those conditions raise serotonin levels, she said, not much is known about what they're actually doing or how they interact with brain.
Hashemi said her team has begun to fill that void, however. In work with antidepressants, which typically must be taken for three to four weeks to have effects in humans, members have found a tenfold increase in the serotonin levels of mice within five minutes.
Most exciting for Hashemi, however, is what CFMs can do when placed into human brains.
Doctors currently must wait for Parkinson's disease patients, for example, to begin having tremors before controlling dopamine levels to make them subside. Patients must be awake for doctors to visually assess the tremor.
Researchers are taking the first step toward a closed-loop system by putting CFMs into a patient's brain and measuring the dopamine. The next step is to construct a system where that information is acted upon by a device that signals the CFM to initiate a dopamine level increase.
"We're almost there," Hashemi said. "It's really only a matter of time before it can mean that the patient has total independence and that the surgeon no longer has to decide, because the decision will be made chemically, which is as it should be."
Such technology could be applied to a wealth of conditions, she said, even depression, which currently is not routinely treated by brain surgery.
"But if we could show that this was the best therapy for it, you could imagine there would be a stimulating electrode in the part of the brain that controls serotonin, and it would be fed back with a device that measures serotonin," Hashemi said. "It could be as easy as that."
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