Abstract

Neurons communicate by releasing neurotransmitters, which diffuse to neighboring cells causing an effect by interacting with a receptor. Changes in neurotransmitter levels within the extra cellular space are an indication of the messages sent between neurons. Measurement of these concentration dynamics in vivo is an important means of understanding neurotransmission and ultimately the brain, brain diseases, and behavior. Present methods for monitoring neurotransmitters in vivo involve sensors or sampling techniques coupled with analysis of fractions. Sensors are powerful yet limited to measuring one compound at a time. Furthermore, sensors for just a few of the over 100 neurotransmitters have been developed. Sampling approaches are limited by temporal resolution of a few minutes whereas neurotransmitter concentrations change on the second time scale. In addition, the large size of sampling probes precludes measurement in many brain regions. The objective of this work is to develop methods of monitoring many neurotransmitters with physiologically and behaviorally relevant temporal and spatial resolution. In this proposal a microfabricated electrophoresis system will be coupled to a microdialysis probe to accomplish high-resolution monitoring of amine neurotransmitters. A novel microsampling probe with over 500-fold better spatial resolution than microdialysis will be developed. Neuropeptide analysis will be improved by developing sampling probes with improved collection efficiencies. In addition, improved sensitivity for neuropeptide measurements will be obtained by interfacing miniaturized capillary chromatography columns to mass spectrometry. The methods will be applied by collaborating with several neuroscience groups for investigation of: 1) taurine/dopamine neurotransmission in ethanol addiction, 2) glutamate/ascorbate interactions in mice engineered to develop Huntington's disease, 3) the in vivo neurochemical effects of an enkephalinase inhibitor (a novel anti-depressant), and 4) the neurochemical signals in sleep.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
9R01EB003320-06
Application #
6579967
Study Section
Special Emphasis Panel (ZRG1-BECM (01))
Program Officer
Moy, Peter
Project Start
1999-05-05
Project End
2008-03-31
Budget Start
2003-04-03
Budget End
2004-03-31
Support Year
6
Fiscal Year
2003
Total Cost
$317,400
Indirect Cost

  Institution

Name
University of Michigan Ann Arbor
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109

  Publications

Zestos, Alexander G; Carpenter, Colleen; Kim, Youngsoo et al. (2018) Ruboxistaurin Reduces Cocaine-Stimulated Increases in Extracellular Dopamine by Modifying Dopamine-Autoreceptor Activity. ACS Chem Neurosci :
Al-Hasani, Ream; Wong, Jenny-Marie T; Mabrouk, Omar S et al. (2018) In vivo detection of optically-evoked opioid peptide release. Elife 7:
Jun, Heejin; Yu, Hui; Gong, Jianke et al. (2018) An immune-beige adipocyte communication via nicotinic acetylcholine receptor signaling. Nat Med 24:814-822
Vollbrecht, Peter J; Nesbitt, Kathryn M; Mabrouk, Omar S et al. (2018) Cocaine and desipramine elicit distinct striatal noradrenergic and behavioral responses in selectively bred obesity-resistant and obesity-prone rats. Behav Brain Res 346:137-143
Carpenter, Colleen; Zestos, Alexander G; Altshuler, Rachel et al. (2017) Direct and Systemic Administration of a CNS-Permeant Tamoxifen Analog Reduces Amphetamine-Induced Dopamine Release and Reinforcing Effects. Neuropsychopharmacology 42:1940-1949
Ngernsutivorakul, Thitaphat; Cipolla, Cynthia M; Dugan, Colleen E et al. (2017) Design and microfabrication of a miniature fiber optic probe with integrated lenses and mirrors for Raman and fluorescence measurements. Anal Bioanal Chem 409:275-285
Vollbrecht, Peter J; Mabrouk, Omar S; Nelson, Andrew D et al. (2016) Pre-existing differences and diet-induced alterations in striatal dopamine systems of obesity-prone rats. Obesity (Silver Spring) 24:670-7
Wong, Jenny-Marie T; Malec, Paige A; Mabrouk, Omar S et al. (2016) Benzoyl chloride derivatization with liquid chromatography-mass spectrometry for targeted metabolomics of neurochemicals in biological samples. J Chromatogr A 1446:78-90
Hamid, Arif A; Pettibone, Jeffrey R; Mabrouk, Omar S et al. (2016) Mesolimbic dopamine signals the value of work. Nat Neurosci 19:117-26
Cui, Qiaoling; Pitt, Jason E; Pamukcu, Arin et al. (2016) Blunted mGluR Activation Disinhibits Striatopallidal Transmission in Parkinsonian Mice. Cell Rep 17:2431-2444

Showing the most recent 10 out of 17 publications