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A Novel Microbiosensor Microarray for Continuous ex Vivo Monitoring of Gamma-Aminobutyric Acid in Real-Time.

ABSTRACT: Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter that is essential for normal brain function. It is involved in multiple neuronal activities, including plasticity, information processing, and network synchronization. Abnormal GABA levels result in severe brain disorders and therefore GABA has been the target of a wide range of drug therapeutics. GABA being non-electroactive is challenging to detect in real-time. To date, GABA is detected mainly via microdialysis with a high-performance liquid chromatography (HPLC) system that employs electrochemical (EC) and spectroscopic methodology. However, these systems are bulky and unsuitable for real-time continuous monitoring. As opposed to microdialysis, biosensors are easy to miniaturize and are highly suitable for in vivo studies; they selectively oxidize GABA into a secondary electroactive product (usually hydrogen peroxide, H2O2) in the presence of enzymes, which is then detected by amperometry. Unfortunately, this method requires a rather cumbersome process with prereactors and relies on externally applied reagents. Here, we report the design and implementation of a GABA microarray probe that operates on a newly conceived principle. It consists of two microbiosensors, one for glutamate (Glu) and one for GABA detection, modified with glutamate oxidase and GABASE enzymes, respectively. By simultaneously measuring and subtracting the H2O2 oxidation currents generated from these microbiosensors, GABA and Glu can be detected continuously in real-time in vitro and ex vivo and without the addition of any externally applied reagents. The detection of GABA by this probe is based upon the in-situ generation of ?-ketoglutarate from the Glu oxidation that takes place at the Glu microbiosensor. A GABA sensitivity of 36 ± 2.5 pA ?M-1cm-2, which is 26-fold higher than reported in the literature, and a limit of detection of 2 ± 0.12 ?M were achieved in an in vitro setting. The GABA probe was successfully tested in an adult rat brain slice preparation. These results demonstrate that the developed GABA probe constitutes a novel and powerful neuroscientific tool that could be employed in the future for in vivo longitudinal studies of the combined role of GABA and Glu (a major excitatory neurotransmitter) signaling in brain disorders, such as epilepsy and traumatic brain injury, as well as in preclinical trials of potential therapeutic agents for the treatment of these disorders.

SUBMITTER: Hossain I

PROVIDER: S-EPMC6090213 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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A Novel Microbiosensor Microarray for Continuous <i>ex Vivo</i> Monitoring of Gamma-Aminobutyric Acid in Real-Time.

Hossain Imran I Tan Chao C Doughty Phillip T PT Dutta Gaurab G Murray Teresa A TA Siddiqui Shabnam S Iasemidis Leonidas L Arumugam Prabhu U PU

Frontiers in neuroscience 20180807

Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter that is essential for normal brain function. It is involved in multiple neuronal activities, including plasticity, information processing, and network synchronization. Abnormal GABA levels result in severe brain disorders and therefore GABA has been the target of a wide range of drug therapeutics. GABA being non-electroactive is challenging to detect in real-time. To date, GABA is detected mainly via microdialysis with a high- ...[more]

PMID: 30131664

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Project description:The study objective was to evaluate whether a novel global position system (GPS)-like position-sensing technology will enable accurate co-registration of images between imaging modalities. Co-registration of images obtained by different imaging modalities will allow for comparison and fusion between imaging modalities, and therefore has significant clinical and research implications. We compared ultrasound (US) and magnetic resonance imaging (MRI) scans of carotid endarterectomy (CEA) specimens using a novel position-sensing technology that uses an electromagnetic (EM) transmitter and sensors mounted on a US transducer. We then evaluated in vivo US-US and US-MRI co-registration.Thirteen CEA specimens underwent 3.0 Tesla MRI, after which images were uploaded to a LOGIQ E9 3D (GE Healthcare, Wauwatosa, WI) US system and registered by identifying two to three common points. A similar method was used to evaluate US-MRI co-registration in patients with carotid atherosclerosis. For carotid intima-media thickness (C-IMT) measurements, 10 volunteers underwent bilateral carotid US scans co-registered to three-dimensional US maps created on the initial visit, with a repeat scan 2 days later.For the CEA specimens, there was a mean of 20 (standard error [SE] 2.0) frames per MRI slice. The mean frame difference, over 33 registration markers, between MRI and US scans for readers 1 and 2 was -2.82 ± 19.32 and 2.09 ± 14.68 (mean ± 95% CI) frames, respectively. The US-MRI intraclass correlation coefficients (ICCs) for the first and second readers were 0.995 and 0.997, respectively. For patients with carotid atherosclerosis, the mean US frames per MRI slice (9 [SE 2.3]) was within range of that observed with CEA specimens. Inter-visit, intra-reader, and inter-reader reproducibility of C-IMT measurements were consistently high (side-averaged ICC >0.9).Accurate co-registration between US and other modalities is feasible with a GPS-like technology, which has significant clinical and research applicability.

Dataset Information

A Novel Microbiosensor Microarray for Continuous ex Vivo Monitoring of Gamma-Aminobutyric Acid in Real-Time.

Publications

A Novel Microbiosensor Microarray for Continuous <i>ex Vivo</i> Monitoring of Gamma-Aminobutyric Acid in Real-Time.

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