Biomedical subjects

Ji-Kyung Choi

Publications and source records attributed to Ji-Kyung Choi.

8 recordsLinked to original sources

PubMed2006

Brain hemodynamic changes mediated by dopamine receptors: Role of the cerebral microvasculature in dopamine-mediated neurovascular coupling.

The coupling between neurotransmitter-induced changes in neuronal activity and the resultant hemodynamic response is central to the interpretation of neuroimaging techniques. In the present study, MRI experiments showed that dopamine transporter blockers such as cocaine and dopamine releasers such as amphetamine and D1 receptor agonists induced large positive increases in relative cerebral blood volume (rCBV) that were not sensitive to nitric oxide synthase inhibition. However, D1/D5 receptor antagonism with SCH-23390 prevented or blocked the hemodynamic response without any concomitant effect on dopamine release. Dopamine D2/D3 receptor agonists, in contrast, induced negative changes in rCBV in brain regions corresponding largely to those endowed with these receptors. D1 and D5 receptor mRNAs were expressed in microvessels of responsive brain areas, while D2 and D3 receptors were not consistently associated with the microvascular bed. D3 receptors had an astroglial localization. Together, these experiments show that direct effects of dopamine upon the vasculature cannot be ignored in measuring the hemodynamic coupling associated with dopaminergic drugs. These results further suggest that this coupling is partially mediated through D1/D5 receptors on the microvasculature leading to increased rCBV and through astroglial D3 receptors leading to decreased rCBV. These data provide additional support for the role of local post-synaptic events in neurovascular coupling and emphasize that the interpretation of fMRI signals exclusively in terms of neuronal activity may be incomplete.

Animals↗

PubMed2006

High resolution spatial mapping of nicotine action using pharmacologic magnetic resonance imaging.

Nicotine is one of the most addictive substances known. To better understand the mechanisms of action, we mapped the regional brain response to nicotine administration using pharmacologic magnetic resonance imaging (phMRI) in rats. We measured the regional response of relative cerebral blood volume (rCBV) in rats to a challenge of 0.07 mg/kg (0.43 micromol/kg) of nicotine. The areas of the brain with significant and reproducible changes in the rCBV response were (in descending order of magnitude) infralimbic cortex, hippocampus (subiculum), agranular insular/pyriform cortex, visual cortex, interpeduncular area, nucleus accumbens, cingulate cortex, thalamus, and septum. This pattern of response is consistent with stimulation of both cholinergic and dopaminergic neuronal pathways and is consistent with the known behavioral properties of nicotine. The peak CBV response to nicotine occurred between 9 and 13 min depending upon brain region, and the average full width half-maximum of the rCBV response was 27 min. The high spatial and temporal resolution of the phMRI technique lends itself well to further, more detailed, studies of nicotine dynamics.

Acetylcholine↗

PubMed2005

Mapping dopamine D2/D3 receptor function using pharmacological magnetic resonance imaging.

RATIONALE: Regulation of dopamine release and synthesis occurs via pre-synaptic dopamine (DA) D2/D3 autoreceptors (DARs). Mapping of DAR function in vivo is difficult and is usually best assessed using invasive measures of DA release, such as microdialysis at discrete sites. We wished to show that pharmacological magnetic resonance imaging (phMRI) may prove useful for this purpose. OBJECTIVE: To demonstrate that the relative cerebral blood volume (rCBV) changes induced by amphetamine can be modulated by DA D2 receptor antagonists and agonists in a manner consistent with modulation of DAR function and to compare these effects with microdialysis. METHODS: We used phMRI with iron oxide contrast agents to map changes in rCBV in response to an amphetamine challenge, pre-treatment and post-treatment with varying doses of the D2 antagonist eticlopride and the D2 agonist quinpirole. We also compared the effects of D2 antagonism using microdialysis measurements of DA release. RESULTS: Antagonism of D2 receptors with eticlopride potentiated rCBV changes induced by amphetamine in the nucleus accumbens and caudate putamen in a dose-dependent manner. The amphetamine-induced increase in rCBV in the accumbens in animals pre-treated with eticlopride was paralleled by a similar percentage increase in DA release measured by means of microdialysis. Conversely, agonism of D2 receptors using quinpirole reduced amphetamine-induced rCBV changes in the caudate putamen and nucleus accumbens. The effects of both quinpirole and eticlopride on amphetamine-induced rCBV changes were largest in the nucleus accumbens. CONCLUSIONS: These results suggest that phMRI may potentially prove useful to map DAR function non-invasively in multiple brain regions simultaneously.

Amphetamine↗

PubMed2005

Mapping interactions between dopamine and adenosine A2a receptors using pharmacologic MRI.

Adenosine receptors in the basal ganglia are implicated in regulation of dopamine function and release. We investigated the interactions between dopamine receptors and adenosine receptors in the basal ganglia using pharmacologic MRI (phMRI) in rats. Stimulation of dopamine receptors was achieved using administration of 2 mg/kg of amphetamine. Then we investigated the antagonism of these changes using the selective A2a receptor antagonist 3,7-dimethyl-1-propargylaxanthine (DMPX). Amphetamine alone caused large increases (10-30%) in relative cerebral blood volume (rCBV) in caudate/putamen (CPu), nucleus accumbens (NAcc), thalamus, and frontal and cingulate cortices with changes that persisted for 70-80 min. DMPX alone (5 mg/kg) induced decreases in rCBV (approximately 8-10%) in NAcc, CPu, and olfactory tubercule, with smaller changes in thalamus (-6%) consistent with the regional distribution of A2a receptors. We examined the interactions between amphetamine and DMPX by assessing the effects of DMPX (5 mg/kg) administration 20 min after injection of 3 mg/kg amphetamine. These experiments showed that DMPX immediately decreased the rCBV increase induced by amphetamine in NAcc, CPu, and thalamus but not in cingulate or sensorimotor cortex. Companion microdialysis experiments showed that dopamine release in CPu was decreased in a similar manner. These experiments demonstrate the utility of phMRI for probing, in a noninvasive manner, the temporal and spatial dynamics of neurotransmitter interactions.

Adenosine A2 Receptor Antagonists↗

PubMed2004

Magnetic resonance spectroscopic analysis of Alzheimer's disease mouse brain that express mutant human APP shows altered neurochemical profile.

Transgenic mice that express mutant human amyloid precursor protein (APPTg2576) develop beta-amyloid (Abeta) plaques throughout the cortex starting at 10-12 months of age. We examined the neurochemical profile of APPTg2576 mice using in vitro and in vivo magnetic resonance spectroscopy (MRS); gross abnormalities using magnetic resonance imaging (MRI) and plaque distribution; size and number using immunohistochemistry. Transgenic mice were anesthetized with halothane and scanned at 4.7 T using T2-weighted imaging and in vivo MRS of frontal cortex. In vitro MRS was run from brain extracts of frontal cortex in both APP and wild-type mice. Mice were also perfused and brains were collected and cut for immunohistochemistry. We found that N-acetylaspartate (NAA), glutamate and glutathione were decreased by 17%, 22% and 36%, respectively, in the cerebral cortex of APP transgenic mice at 19 months of age when Abeta deposits are widespread. Taurine was increased 21% compared to wild-type. Decreased levels of NAA and increased levels of taurine are consistent with decreased neuronal viability and increased glial volume, and are similar to findings of decreased NAA and increased myo-inositol in human Alzheimer's disease (AD) brains. Correlation between the severity of Abeta deposition and altered neurochemical profile remains to be studied. Nevertheless, the altered neurochemical profile may be a valuable marker to test therapeutics in this mouse model.

Alzheimer Disease↗

PubMed2004

Basal ganglia activity remains elevated after movement in focal hand dystonia.

Although previous studies of focal hand dystonia have detected cortical sensorimotor abnormalities, little is known about the role of the basal ganglia in this disorder. We report here that when focal hand dystonic patients performed finger-tapping tasks, functional magnetic resonance imaging showed persisting elevations of basal ganglia activity after the tasks ended. We posit that inhibitory control of the basal ganglia may be faulty in focal hand dystonia, and that the increases we observe in "resting" activity may mask basal ganglia abnormalities in standard imaging contrast analyses.

Adult↗

PubMed2004

Exogenous contrast agent improves sensitivity of gradient-echo functional magnetic resonance imaging at 9.4 T.

Relative to common clinical magnetic field strengths, higher fields benefit functional brain imaging both by providing additional signal for high-resolution applications and by improving the sensitivity of endogenous contrast due to the blood oxygen level dependent (BOLD) mechanism, which has limited detection power at low magnetic fields relative to the use of exogenous contrast agent. This study evaluates the utility of iron oxide contrast agent for gradient echo functional MRI at 9.4 T in rodents using cocaine and methylphenidate as stimuli. Relative to the BOLD method, the use of high iron doses and short echo times provided a roughly twofold global increase in functional sensitivity, while also suppressing large vessel signal and reducing susceptibility artifacts. Furthermore, MRI measurements of the functional percentage change in cerebral blood volume (CBV) showed excellent agreement with results obtained at much lower magnetic field strengths, demonstrating that MRI estimates of this quantity are roughly independent of magnetic field when appropriate techniques are employed. The derived field dependencies for relative sensitivity and MRI estimates of the percentage change in CBV suggest that the benefits provided by exogenous agents will persist even at much higher magnetic fields than 9.4 T.

Analysis of Variance↗

PubMed2002

Interactions of very long-chain saturated fatty acids with serum albumin.

The remarkable binding properties of serum albumin have been investigated extensively, but little is known about an important class of fatty acids, the very long-chain saturated fatty acids (VLCFA; >18 carbons). Although VLCFA are metabolized efficiently in normal individuals, they are markers for and possibly causative agents of several peroxisomal disorders. We studied the binding of [(13)C]carboxyl-enriched arachidic (C20:0), behenic (C22:0), lignoceric (C24:0), and hexacosanoic (C26:0) acids to bovine serum albumin (BSA) by (13)C-NMR spectroscopy. For each VLCFA, the NMR spectra showed multiple signals at chemical shifts previously identified for long-chain fatty acids (12-18 carbons), suggesting stabilization of binding by similar, if not identical, interactions of the fatty acid carboxyl anion with basic amino acid residues. The maximal binding (mol of VLCFA/mol of BSA) and the number of observed binding sites decreased with increasing chain length, from 4-5 for C20:0, 3-4 for C22:0, and 2 for C24:0; we validated our previous conclusion that BSA has only one site for C26:0 (Ho, J. K., H. Moser, Y. Kishimoto, and J. A. Hamilton. 1995. J. Clin. Invest. 96: 1455-1463). Analysis of chemical shifts suggested that the highest affinity sites for VLCFA are low affinity sites for long-chain fatty acids. In competition experiments with (13)C-labeled C22:0 (3 mol/mol of BSA) and unlabeled oleic acid, C22:0 bound to BSA in the presence of up to 4 mol of oleic acid/mol of BSA, but 1 mol was shifted into a different site. Our studies suggest that albumin has adequate binding capacity for the low plasma levels of VLCFA with 20 to 26 carbons, but the protein may not be able to bind longer chain VLCFA.

Animals↗