Abstract
The brain is one of the most complex biological structures known to science. How it works or, more specifically, how the physical brain gives rise to the properties of mind remains an unanswered question. However, it is clear that many drugs used empirically in the treatment of neurological disorders, such as Parkinson’s disease, work through their specific chemical actions on nerve cells in the brain. Thus, if we are to understand brain function and drug performance, there is a need to measure chemical signalling in the brain. Measurement technologies for neurochemical studies in the living brain include spectroscopy, such as NMR, sampling techniques, such as cerebral microdialysis, and the topic of this chapter - in situ electrochemical monitoring using long-term in vivo electrochemistry (LIVE). With LIVE, a microvoltammetric sensor is implanted in a specific brain region to monitor local changes in the concentration of specific substances in the extracellular fluid. It can do this with sub-second time resolution and with measurement periods extending over many hours, potentially days. Spatially, localised, high-temporal resolution, long-term sensing of this kind allows investigations of the functions of chemicals in neuronal signalling, drug actions and well-defined behaviours. In this chapter, we give an overview of the different electrochemical sensor types, the techniques used and the principal neurochemicals potentially associated with Parkinson’s disease that can be measured in vivo.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsAbbreviations
- 3MT:
-
3-Methoxytyramine
- 5HIAA:
-
5-Hydroxyindoleacetic acid
- 5HT:
-
5-Hydroxytryptamine
- AA:
-
Ascorbic acid
- CAT:
-
Catalase
- CEE:
-
Carbon epoxy electrode
- CFE:
-
Carbon fibre electrode
- CNS:
-
Central nervous system
- CPA:
-
Constant potential amperometry
- CPE:
-
Carbon paste electrode
- CV:
-
Cyclic voltammetry
- DA:
-
Dopamine
- DOPAC:
-
3,4-Dihydroxyphenylacetic acid
- DPA:
-
Differential pulse amperometry
- DPV:
-
Differential pulse voltammetry
- ECF:
-
Extracellular fluid
- FCV:
-
Fast cyclic voltammetry
- GA:
-
Glutaraldehyde
- GluOx:
-
Glutamate oxidase
- GOx:
-
Glucose oxidase
- HPLC:
-
High-performance liquid chromatography
- HVA:
-
Homovanillic acid
- LIVE:
-
Long-term in vivo electrochemistry
- l-NAME:
-
N ω-nitro-l-arginine methyl ester
- LSV:
-
Linear sweep voltammetry
- NA:
-
Noradrenaline
- NMR:
-
Nuclear magnetic resonance spectroscopy
- NO:
-
Nitric oxide
- NOS:
-
Nitric oxide synthase
- o-PPD:
-
Poly(o-phenylenediamine)
- PD:
-
Parkinson’s disease
- SCE:
-
Saturated calomel electrode
- SCV:
-
Staircase voltammetry
- UA:
-
Uric acid
References
Crespi F, Croce AC, Fiorani S, Masala B, Heidbreder C, Bottiroli G (2004) Autofluorescence spectrofluorometry of central nervous system (CNS) neuromediators. Lasers Surg Med 34:39
Parkin MC, Hopwood SE, Strong AJ, Boutelle MG (2003) Resolving dynamic changes in brain metabolism using biosensors and on-line microdialysis. Trends Anal Chem 22:487
O’Neill RD, Chang SC, Lowry JP, McNeil CJ (2004) Comparisons of platinum, gold, palladium and glassy carbon as electrode materials in the design of biosensors for glutamate. Biosens Bioelectron 19:1521
Lada MW, Kennedy RT (1996) Quantitative in vivo monitoring of primary amines in rat caudate nucleus using microdialysis coupled by a flow-gated interface to capillary electrophoresis with laser-induced fluorescence detection. Anal Chem 68:2790
Pantano P, Khur WG (1995) Enzyme-modified microelectrodes for in vivo neurochemical measurements. Electroanalysis 7:405
O’Neill RD, Lowry JP, Mas M (1998) Monitoring brain chemistry in vivo: voltammetric techniques, sensors, and behavioral applications. Crit Rev Neurobiol 12:69
Lowry JP, O’Neill RD (2005) Neuroanalytical chemistry in vivo using biosensors. In: Grimes CA and Dickey EC (eds) Encyclopedia of sensors. American Scientific Publishers, CA, ISBN: 1-58883-062-4, pp. 501–524
Kissinger PT, Hart JB, Adams RN (1973) Voltammetry in brain tissue–a new neurophysiological measurement. Brain Res 55:209
Clark LC Jr, Misrahy G, Fox RP (1958) Chronically implanted polarographic electrodes. J Appl Physiol 13:85
Clark LC Jr, Lyons C (1965) Studies of a glassy carbon electrode for brain polarography with observations on the effect of carbonic anhydrase inhibition. Ala J Med Sci 2:353
Ronkainen NJ, Halsall HB, Heineman WR (2010) Electrochemical biosensors. Chem Soc Rev 39:1747
Nicholson C, Sykova E (1998) Extracellular space structure revealed by diffusion analysis.Trends Neurosci 21:207
Michael AC, Borland LM (2007) Electrochemical methods for neuroscience. CRC Press, Boca Raton, FL
Shibuki K (1990) An electrochemical microprobe for detecting nitric oxide release in brain tissue. Neurosci Res 9:69
Clark LC Jr (1956) Monitor and control of blood and tissue O2 tensions. T Am Soc Art Int Org 2:41
Malinski T, Taha Z (1992) Nitric oxide release from a single cell measured in situ by a porphyrinic-based microsensor. Nature 358:676
Mas M, Escrig A, Gonzalez-Mora JL (2002) In vivo electrochemical measurement of nitric oxide in corpus cavernosum penis. J Neurosci Methods 119:143
Friedemann MN, Robinson SW, Gerhardt GA (1996) o-Phenylenediamine-modified carbon fiber electrodes for the detection of nitric oxide. Anal Chem 68:2621
Park JK, Tran PH, Chao JK, Ghodadra R, Rangarajan R, Thakor NV (1998) In vivo nitric oxide sensor using non-conducting polymer-modified carbon fiber. Biosens Bioelectron 13:1187
Pontie M (2000) Electrochemical nitric oxide microsensors: sensitivity and selectivity characterisation Anal Chim Acta 411:175
Brown FO, Lowry JP (2003) Microelectrochemical sensors for in vivo brain analysis: an investigation of procedures for modifying Pt electrodes using Nafion. Analyst 128:700
Brown FO, Finnerty NJ, Lowry JP (2009) Nitric oxide monitoring in brain extracellular fluid: characterisation of Nafion-modified Pt electrodes in vitro and in vivo. Analyst 134:2012
Palsson E, Finnerty N, Fejgin K, Klamer D, Wass C, Svensson L, Lowry J (2009) Increased cortical nitric oxide release after phencyclidine administration. Synapse 63:1083
Fejgin K, Palsson E, Wass C, Svensson L, Klamer D (2007) Nitric oxide signaling in the medial prefrontal cortex is involved in the biochemical and behavioral effects of phencyclidine. Neuropsychopharmacology 33:1874
Chen BT, Avshalumov MV, Rice ME (2001) H(2)O(2) is a novel, endogenous modulator of synaptic dopamine release. J Neurophysiol 85:2468
Hyslop PA, Zhang ZY, Pearson DV, Phebus LA (1995) Measurement of striatal H2O2 by microdialysis following global forebrain ischemia and reperfusion in the rat: correlation with the cytotoxic potential of H2O2 in vitro. Brain Res 671:181
Lei BP, Adachi N, Nagaro T, Arai T (1997) The effect of dopamine depletion on the H2O2 production in the rat striatum following transient middle cerebral artery occlusion. Brain Res 764:299
Layton ME, Pazdernik TL, Samson FE (1997) Cerebral penetration injury leads to H2O2 generation in microdialysis samples. Neurosci Lett 236:63
O’Neill RD, Lowry JP, Rocchitta G, McMahon CP, Serra PA (2008) Designing sensitive and selective polymer/enzyme composite biosensors for brain monitoring in vivo. Trends Anal Chem 27:78
Kulagina NV, Michael AC (2003) Monitoring hydrogen peroxide in the extracellular space of the brain with amperometric microsensors. Anal Chem 75:4875
O’Brien KB, Killoran SJ, O’Neill RD, Lowry JP (2007) Development and characterization in vitro of a catalase-based biosensor for hydrogen peroxide monitoring. Biosens Bioelectron 22:2994
Sanford AL, Morton SW, Whitehouse KL, Oara HM, Lugo-Morales LZ, Roberts JG, SombersLA (2010) Voltammetric detection of hydrogen peroxide at carbon fiber microelectrodes. Anal Chem 82:5205–5210
Clark LC Jr, Clark EW (1964) Epicardial oxygen measured with a pyrolytic graphite electrode. Ala J Med Sci 1:142
Bolger FB, McHugh SB, Bennett R, Li J, Ishwari K, Francois J, Conway MW, Gilmour G, Bannerman DM, Fillenz M, Tricklebank M, Lowry JP (2011) Characterisation of carbon paste electrodes for real-time amperometric monitoring of brain tissue oxygen. J Neurosci Methods 195:135
Bolger FB, Bennett R, Lowry JP (2011) An in vitro characterisation comparing carbon paste and Pt microelectrodes for real-time detection of brain tissue oxygen. Analyst 136:4028
Lowry JP, Boutelle MG, O’Neill RD, Fillenz M (1996) Characterization of carbon paste electrodes in vitro for simultaneous amperometric measurement of changes in oxygen and ascorbic acid concentrations in vivo. Analyst 121:761
Bolger FB, Lowry JP (2005) Brain tissue oxygen: in vivo monitoring with carbon paste electrodes. Sensors 5:473 567
Lowry JP, Boutelle MG, Fillenz M (1997) Measurement of brain tissue oxygen at a carbon paste electrode can serve as an index of increases in regional cerebral blood flow. J Neurosci Methods 71:177
Lowry JP, Griffin K, McHugh SB, Lowe AS, Tricklebank M, Sibson NR (2010) Real-time electrochemical monitoring of brain tissue oxygen: a surrogate for functional magnetic resonance imaging in rodents. Neuroimage 52:549
Bazzu G, Puggioni GGM, Dedola S, Calia G, Rocchitta G, Migheli R, Desole MS, Lowry JP, O’Neill RD, Serra PA (2009) Real-time monitoring of brain tissue oxygen using a miniaturized biotelemetric device implanted in freely moving rats. Anal Chem 81:2235
Revsbech NP (1989) An oxygen microsensor with a guard cathode. Limnol Oceanogr 34:474
Offenhauser N, Thomsen K, Caesar K, Lauritzen M (2005) Activity-induced tissue oxygenation changes in rat cerebellar cortex: interplay of postsynaptic activity and cerebral blood flow. J Physiol 565:279
Piilgaard H, Lauritzen M (2009) Persistent increase in oxygen consumption and impaired neurovascular coupling after spreading depression in rat neocortex. J Cereb Blood Flow Metab 29:1517
Hu Y, Mitchell KM, Albahadily FN, Michaelis EK, Wilson GS (1994) Direct measurement of glutamate release in the brain using a dual enzyme-based electrochemical sensor. Brain Res 659:117
Hu Y, Wilson GS (1997) Rapid changes in local extracellular rat brain glucose observed with an in vivo glucose sensor. J Neurochem 68:1745
Hu Y, Wilson GS (1997) A temporary local energy pool coupled to neuronal activity: fluctuations of extracellular lactate levels in rat brain monitored with rapid-response enzyme-based sensor. J Neurochem 69:1484
Lowry JP, McAteer K, El Atrash SS, Duff A, O’Neill RD (1994) Characterization of glucose oxidase-modified poly(phenylenediamine)-coated electrodes in vitro and in vivo: homogeneous interference by ascorbic acid in hydrogen peroxide detection. Anal Chem 66:1754
Lowry JP, Miele M, O’Neill RD, Boutelle MG, Fillenz M (1998) An amperometric glucose-oxidase/poly(o-phenylenediamine) biosensor for monitoring brain extracellular glucose: in vivo characterisation in the striatum of freely-moving rats. J Neurosci Methods 79:65
Lowry JP, Ryan MR, O’Neill RD (1998) Behaviourally induced changes in extracellular levels of brain glutamate monitored at 1 s resolution with an implanted biosensor. Anal Commun 35:87
Lowry JP, Ryan MR, O’Neill RD (2001) Interference in biosensor detection of brain glutamate in vivo: possible role of endogenous ECF hydrogen peroxide. Monitoring molecules in neuroscience. University College Dublin, Dublin, Ireland.
Kulagina NV, Shankar L, Michael AC (1999) Monitoring glutamate and ascorbate in the extracellular space of brain tissue with electrochemical microsensors. Anal Chem 71:5093
Oldenziel WH, Westerink BHC (2005) Improving glutamate microsensors by optimizing the composition of the redox hydrogel. Anal Chem 77:5520
Oldenziel WH, Beukema W, Westerink BHC (2004) Improving the reproducibility of hydrogel-coated glutamate microsensors by using an automated dipcoater. J Neurosci Methods 140:117
Oldenziel WH, de Jong LAA, Dijkstra G, Cremers TIFH, Westerink BHC (2006) Improving the performance of glutamate microsensors by purification of ascorbate oxidase. Anal Chem 78:2456
Oldenziel WH, Dijkstra G, Cremers TIFH, Westerink BHC (2006) In vivo monitoring of extracellular glutamate in the brain with a microsensor. Brain Res 1118:34
Oldenziel WH, Dijkstra G, Cremers TIFH, Westerink BHC (2006) Evaluation of hydrogel-coated glutamate microsensors. Anal Chem 78:3366
Burmeister JJ, Gerhardt GA (2001) Self-referencing ceramic-based multisite microelectrodes for the detection and eliminiation of interferences from the measurement of l-glutamate and other analytes. Anal Chem 73:1037
Albery WJ, Boutelle MG Galley PT (1992) The dialysis electrode—a new method for in vivo monitoring. J Chem Soc, Chem Commun 12:900
Walker MC, Galley PT, Errington ML, Shorvon SD, Jefferys JGR (1995) Ascorbate and glutamate release in the rat hippocampus after perforant path stimulation: a “dialysis electrode” study. J Neurochem 65
Asai S, Iribe Y, Kohno T, Ishikawa K (1996) Real time monitoring of biphasic glutamate release using dialysis electrode in rat acute brain ischemia. Neuroreport 7:1092
Kohno T, Asai S, Iribe Y, Hosoi I, Shibata K, Ishikawa K (1998) An improved method for the detection of changes in brain extracellular glutamate levels. J Neurosci Methods 81:199
Pellerin L, Magistretti PJ (1994) Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc Natl Acad Sci 91:10625
Fillenz M (2005) The role of lactate in brain metabolism. Neurochem Int 47:413
Pellerin L (2003) Lactate as a pivotal element in neuron-glia metabolic cooperation. Neurochem Int 43:331
Chih C-P, Lipton P, Roberts EL Jr (2001) Do active cerebral neurons really use lactate rather than glucose? Trends Neurosci 24:573
Demestre M, Boutelle MG, Fillenz M (1997) Stimulated release of lactate in freely moving rats is dependent on the uptake of glutamate. J Physiol 499:825
Burmeister JJ, Palmer M, Gerhardt GA (2005) l-Lactate measures in brain tissue with ceramic-based multisite microelectrodes. Biosens Bioelectron 20:1772
McMahon CP, Rocchitta G, Serra PA, Kirwan SM, Lowry JP, O’Neill RD (2006) The efficiency of immobilised glutamate oxidase decreases with surface enzyme loading: an electrostatic effect, and reversal by a polycation significantly enhances biosensor sensitivity. Analyst 131:68
Serra PA, Puggioni G, Bazzu G, Calia G, Migheli R, Rocchitta G (2010) Design and construction of a distributed sensor NET for biotelemetric monitoring of brain energetic metabolism using microsensors and biosensors. Biosensors 241
Shram NF, Netchiporouk LI,Martelet C, Jaffrezic-Renault N, Cespuglio R (1997) Brain glucose: voltammetric determination in normal and hyperglycaemic rats using a glucose microsensor. Neuroreport 8:1109
Shram NF, Netchiporouk LI, Martelet C, Jaffrezic-Renault N, Bonnet C, Cespuglio R (1998) In vivo voltammetric detection of rat brain lactate with carbon fiber microelectrodes coated with lactate oxidase. Anal Chem 70:2618
Shram N, Netchiporouk L, Cespuglio R (2002) Lactate in the brain of the freely moving rat: voltammetric monitoring of the changes related to the sleep–wake states. Eur J Neurosci 16:461
Ikegami Y, Maeda M, Yokota A, Hayashida Y (1997) Cerebral extracellular lactate concentration and blood flow during chemical stimulation of the nucleus tractus solitarii in anesthetized rats. Brain Res 758:33
Bolger FB, Serra PA, O’Neill RD, Fillenz M, Lowry JP (2006) Real-time monitoring of brain extracellular lactate. In: Di Chiara G, Carboni E, Valentini V, Acquas E, Bassareo V, Cadoni C (eds) Monitoring molecules in neuroscience. University of Cagliari, Cagliari, Italy, p 286
Cloutier M, Bolger F, Lowry J, Wellstead P (2009) An integrative dynamic model of brain energy metabolism using in vivo neurochemical measurements.J Comput Neurosci 27:391
Bao L, Avshalumov MV, Patel JC, Lee CR,Miller EW, Chang CJ, RiceME (2009) Mitochondria are the source of hydrogen peroxide for dynamic brain-cell signaling. J Neurosci 29:9002
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media New York
About this chapter
Cite this chapter
Bolger, F.B., Finnerty, N.J., Lowry, J.P. (2012). Real-Time In Vivo Sensing of Neurochemicals. In: Wellstead, P., Cloutier, M. (eds) Systems Biology of Parkinson's Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3411-5_6
Download citation
DOI: https://doi.org/10.1007/978-1-4614-3411-5_6
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4614-3410-8
Online ISBN: 978-1-4614-3411-5
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)