<i>In vivo</i>brain microdialysis: advances in neuropsychopharmacology and drug discovery

Darvesh, Altaf S.; Carroll, Richard T.; Geldenhuys, Werner J.; Gudelsky, Gary A.; Klein, Jochen; Meshul, Charles K.; Schyf, Cornelis J. Van der

doi:10.1517/17460441.2011.547189

Cited by 71 publications

(46 citation statements)

References 146 publications

(162 reference statements)

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“…A major advantage of in vivo microdialysis over voltammetry measurements is the ability to detect neurotransmitters and their metabolites simultaneously (Arbuthnott et al, 1990; Darvesh et al, 2011). We find that extracellular metabolite:DA ratios are almost double in G2019S mice (~600) compared to the values obtained for WT animals (~300).…”

Section: Discussionmentioning

confidence: 99%

Progressive dopaminergic alterations and mitochondrial abnormalities in LRRK2 G2019S knock-in mice

Yue

Hinkle

Davies

et al. 2015

Neurobiology of Disease

228

214

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Mutations in the LRRK2 gene represent the most common genetic cause of late onset Parkinson’s disease. The physiological and pathological roles of LRRK2 are yet to be fully determined but evidence points towards LRRK2 mutations causing a gain in kinase function, impacting on neuronal maintenance, vesicular dynamics and neurotransmitter release. To explore the role of physiological levels of mutant LRRK2, we created knock in mice harboring the most common LRRK2 mutation G2019S in their own genome. We have performed comprehensive dopaminergic, behavioral and neuropathological analyses in this model up to 24 months of age. We find elevated kinase activity in the brain of both heterozygous and homozygous mice. Although normal at 6 months, by 12 months of age, basal and pharmacologically induced extracellular release of dopamine is impaired in both heterozygous and homozygous mice, corroborating previous findings in transgenic models over-expressing mutant LRRK2. Via in vivo microdialysis measurement of basal and drug- evoked extracellular release of dopamine and its metabolites, our findings indicate that exocytotic release from the vesicular pool is impaired. Furthermore, profound mitochondrial abnormalities are evident in the striatum of older homozygous G2019S mice, which are consistent with mitochondrial fission arrest. We anticipate the G2019S will be a useful pre-clinical model for further evaluation of early mechanistic events in LRRK2 pathogenesis and for second-hit approaches to model disease progression.

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Section: Discussionmentioning

confidence: 99%

Progressive dopaminergic alterations and mitochondrial abnormalities in LRRK2 G2019S knock-in mice

Yue

Hinkle

Davies

et al. 2015

Neurobiology of Disease

228

214

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“…Microdialysis is versatile because it can be used to sample from organs, tissues, tumors, and body fluids. 4–8 …”

Section: Introductionmentioning

confidence: 99%

Microfabrication and in Vivo Performance of a Microdialysis Probe with Embedded Membrane

et al. 2016

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Microdialysis sampling is an essential tool for in vivo neurochemical monitoring. Conventional dialysis probes are over 220 μm in diameter and have limited flexibility in design because they are made by assembly using preformed membranes. The probe size constrains spatial resolution and governs the amount of tissue damaged caused by probe insertion. To overcome these limitations, we have developed a method to microfabricate probes in Si that are 45 μm thick × 180 μm wide. The probes contain a buried, U-shaped channel that is 30 μm deep × 60 μm wide and terminates in ports for external connection. A 4 mm length of the probe is covered with a 5 μm thick nanoporous membrane. The membrane was microfabricated by deep reactive ion etching through a porous aluminum oxide layer. The microfabricated probe has cross-sectional area that is 79% less than that of the smallest conventional microdialysis probes. The probes yield 2–7% relative recovery at 100 nL/min perfusion rate for a variety of small molecules. The probe was successfully tested in vivo by sampling from the striatum of live rats. Fractions were collected at 20 min intervals (2 μL) before and after an intraperitoneal injection of 5 mg/ kg amphetamine. Analysis of fractions by liquid chromatography-mass spectrometry revealed reliable detection of 13 neurochemicals, including dopamine and acetylcholine, at basal conditions. Amphetamine evoked a 43-fold rise in dopamine, a result nearly identical to a conventional dialysis probe in the same animal. The microfabricated probes have potential for sampling with higher spatial resolution and less tissue disruption than conventional probes. It may also be possible to add functionality to the probes by integrating other components, such as electrodes, optics, and additional channels.

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“…Dopaminergic pallidal innervation has not been characterized in healthy humans. In nonhuman primates as well as in patients with PD, it mainly derives from nigral projections …”

mentioning

confidence: 99%

Intraoperative dopamine release during globus pallidus internus stimulation in Parkinson's disease

et al. 2013

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In vivobrain microdialysis: advances in neuropsychopharmacology and drug discovery

Cited by 71 publications

References 146 publications

Progressive dopaminergic alterations and mitochondrial abnormalities in LRRK2 G2019S knock-in mice

Progressive dopaminergic alterations and mitochondrial abnormalities in LRRK2 G2019S knock-in mice

Microfabrication and in Vivo Performance of a Microdialysis Probe with Embedded Membrane

Intraoperative dopamine release during globus pallidus internus stimulation in Parkinson's disease

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