• The Korean Journal of Physiology and Pharmacology
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• v.1 no.1
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• pp.1-12
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• 1997

As it has been reported that the depolarization induced acetylcholine (ACh) release is modulated by activation of presynaptic $A_1$ adenosine heteroreceptor and various evidence suggest that indicate the $A_2$ adenosine receptor is present in the striatum, this study was undertaken to delineate the role of adenosine receptors on the striatal ACh release. Slices from the rat striatum were equilibrated with $[^3H]$choline and then the release amount of the labelled product, $[^3H]$ACh, which was evoked by electrical stimulation (rectangular pulses, 3 Hz, 2 ms, 24 mA, $5\;Vcm^{-1}$, 2 min), was measured, and the influence of various agents on the evoked tritium outflow was investigated. And also, quantitative receptor autoradiography and drug-receptor binding assay were performed in order to confirm the presence and characteristics of $A_1$ and $A_2$ adenosine receptors in the rat striatum. Adenosine $(10{sim}100\;{mu}M)$ and $N^6$-cyclopentyladenosine (CPA, $1{sim}100\;{mu}M)$ decreased the $[^3H]$ACh release in a dose-dependent manner without changing the basal rate of release in the rat striatum. The reducing effects of ACh release by adenosine and CPA were abolished by 8-cyclopentyl-1,3-dipropy-Ixanthine (DPCPX, 2 ${mu}M$), a selective $A_1$, adenosine receptor antagonist, treatment. The effect of adenosine was potentiated markedly by 3,7-dimethyl-1-propargylxanthine (DMPX, 10 ${mu}M$), a specific $A_2$ adenosine receptor antagonist. 2-P-(2-carboxyethyl)phenethylamimo-5'-N- ethylcarboxamidoadenosine hydrochloride (CGS-21680C), in concentrations ranging from 0.01 to 10 ${mu}M$, a recently introduced potent $A_2$ adenosine receptor agonist, increased the $[^3H]$ACh release in a dose related fashion without changing the basal rate of release. These effects were completely abolished by DMPX $(10\;{mu}M)$. In autoradiograrhy experiments, $[^3H]$2-chloro-$N^6$-cyclopentyladenosine ($[^3H]$ CCPA) bindings were highly localized in the hippocampus and the cerebral cortex. Additionally, lower levels of binding were found in the striatum. However, $[^3H]$CGS-21680C bindings were highly localized in the striatal region with the greatest density of binding found in the caudate nucleus and putamen. Lower levels of binding were also found in the nucleus accumbens and olfactory tubercle. In drug-receptor binding assay, binding of $[^3H]$ CCPA to $A_1$ adenosine receptors of rat striatal membranes was inhibited by CPA ($K_i$ = 1.6 nM) and N-ethylcarboxamidoadenosine (NECA, $K_i$ = 12.9 nM), but not by CGS-21680C ($K_i$ = 2609.2 nM) and DMPX ($K_i$ = 19,386 nM). In contrast, $[^3H]$CGS-21680C binding to $A_2$ denosine receptors was inhibited by CGS-21680C ($K_i$ = 47.6 nM) and NECA ($K_i$ = 44.9 nM), but not by CPA ($K_i$ = 2099.2 nM) and DPCPX ($K_i$ = 19,207 nM). The results presented here suggest that both types of $A_1$ and $A_2$ adenosine heteroreceptors exist and play an important role in ACh release in the rat striatal cholinergic neurons.

• Progress in Medical Physics
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• v.14 no.2
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• pp.108-123
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• 2003

The purpose of this study is to evaluate the contribution of $^{18}$ F-FDG brain PET in the differentiating Idiopathic parkinson's diesease (IPD), progressive supranuclear palsy (PSP), and multiple system atrophy (MSA). We studied 24 patients with parkinsonism : 8 patients (mean age 67.9$\pm$10.7 y: M/F : 3/5) with IPD, 9 patients (57.9$\pm$9.2 y : M/F : 4/5) with MSA and 7 patients (67.6$\pm$4.8 y : M/F 3/4) with PSP. All patients with parkinsonism and 22 age-matched normal controls underwent $^{18}$ F FDG PET in 3D mode after the injection of 370 MBq $^{118}$ F FDG. The patients with IPD, MSh and PSP were compared with a normal control group by a two-sided t-test of SPM99 (uncorrected P<0.001, extent threshold>100 voxel). All three parkinsonism groups, showed significant hypometabolism in the cerebral neocortex compared to the normal control group. However, the three groups displayed different metabolism in the subcortical structure, brain stem, and cerebellum. In IPD, there was no significant hypometabolism in the putamen, brain stem and cerebellum. However, MSA patients showed significant hypometabolism in the striatum, pons, and cerebellum compared to the normal controls and IPD patients. In addition, PSP showed significant hypometabolism in the caudate nuclei, the thalamus, midbrain, and the cingulate gyrus compared to the normal controls, the IPD, and MSA groups (IPD vs Normal sensitivity/specificity : 75%/l00%, MSA vs Normal sensitivity/specificity :100%/87%, PSP vs Normal sensitivity/specificity : 86%/94%). Our results show that the regional metabolism of IPD, MSA, and PSP is different mainly in the striatum, thalamus, brain stem and cerebellum. An assessment of the $^{18}$ F-FDG PET scan images using SPM may be a useful adjunct to a clinical examination in making a differential diagnosis of Parkinsonism.

• Nuclear Medicine and Molecular Imaging
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• v.40 no.1
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• pp.40-47
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• 2006

Purpose: The aim of this study was to examine the effects of attenuation correction (AC) and scatter correction (SC) on the quantification of PET count rates. Materials and Methods: To assess the effects of AC and SC $^{18}F$-FDG PET images of phantom and cat brain were acquired using microPET R4 scanner. Thirty-minute transmission images using $^{68}Ge$ source and emission images after injection of FDG were acquired. PET images were reconstructed using 2D OSEM. AC and SC were applied. Regional count rates were measured using ROIs drawn on cerebral cortex including frontal, parietal, and latral temporal lobes and deep gray matter including head of caudate nucleus, putamen and thalamus for pre- and post-AC and SC images. The count rates were then normalized with the injected dose per body weight. To assess the effects of AC, count ratio of "deep gray matter/cerebral cortex" was calculated. To assess the effects of SC, ROIs were also drawn on the gray matter (GM) and white matter (WM), and contrast between them ((GM-WM)/GM was measured. Results: After the AC, count ratio of "deep gray matter/cerebral cortex" was increased by $17{\pm}7%$. After the SC, contrast was also increased by $12{\pm}3%$. Conclusion: Relative count of deep gray matter and contrast between gray and white matters were increased after AC and SC, suggesting that the AC would be critical for the quantitative analysis of cat brain PET data.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.23 no.1
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• pp.25-30
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• 2023

Leigh syndrome is a rare progressive neurodegenerative mitochondrial disorder with clinical and genetic heterogeneity. Recently, balletic IARS2 variants have been identified in a number of patients presenting broad clinical phenotypes from Leigh and West syndrome to a rare syndrome CAGSSS characterized by cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia syndrome (OMIM#616007). We describe a child with Korean Leigh syndrome with urologic manifestations resulting from a compound heterozygote mutation in IARS2. A 5-year-old girl visited the emergency room with a complaint of abdominal pain accompanied by abdominal distension. Abdominal-pelvic CT showed a markedly distended urinary bladder without definite obstructive lesions. She was diagnosed with neurogenic bladder dysfunction based on a urodynamic study. She had global delayed development due to neurologic regression after 6 months of age and a history of bilateral cataract surgery at the age of 2 years. Her brain magnetic resonance imaging showed symmetrically increased signal intensities in the bilateral putamen and caudate nuclei with diffuse cerebral atrophy. No gene variants were identified through whole-mitochondrial genome analysis. Whole exome sequencing was performed for diagnosis, and compound heterozygous pathogenic variants were identified in IARS2: c.2446C>T (p. Arg816Ter) and c.2450G>A (p. Arg817His). To the best of our knowledge, this is the first case report of bladder dysfunction manifestation in a patient with IARS2-related Leigh syndrome. Thus, it broadens the clinical and genetic spectrum of IARS2-associated diseases.

• Sleep Medicine and Psychophysiology
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• v.5 no.1
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• pp.54-70
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• 1998

Objectives : The purpose of this study is to evaluate the role of structural and functional changes of the brain in the pathophysiology of schizophrenia. Methods : The authors measured the regions of interest on the magnetic resonance imaging of the brain in 20 patients with paranoid schizophrenia(15 men and 5 women) and 23 control subjects(15 men and 8 women). We also assessed the neurocognitive functions with the Wisconsin Card Sorting Test, the Benton Neuropsychological Assessment, and the Weschler IQ test-Korean version, soft neurologic signs, and psychiatric symptoms in the patient group. Results : In the patient group, all ventricles and basal ganglia including caudate nucleus and globus pallidus were significantly enlarged. Although there were no significant differences between the two groups in the values of right frontal lobe and left temporal lobe, there was a tendency of decrease in the values of right frontal lobe and left temporal lobe. There were significant positive correlations between the values of ventricles and the frequency of previous hospitalization. However, there were no significant correlations between other values of regions of interest and clinical data. The value of the right frontal lobe was significantly correlated with the score of soft neurologic signs, which is suggestive of the neurodevelopmental abnormalities. There were significant correlations between the value of frontal lobe and the scores of the various subscales of Benton Neuropsychiatric Inventory. In contrast, the value of left amygdala and putamen showed significant correlation with the score of verbal IQ on the Weschler IQ test. Structural changes of the temporal lobe areas were related with the positive and general symptom scores on PANSS, while those of the basal ganglia were related with the negative symptom scores. Conclusions : These results suggest that the structural changes of the brain in the patients with schizophrenia show the dual process, which is suggestive that the enlarged ventricle show the neurodegenerative process, while enlarged basal ganglia, and shrinked right frontal and left temporal lobe show the neurodevelopmental abnormalities. Among these changes, structural changes of the frontal lobe related with various neuropsychological deficits, while those of left temporal lobe related with language abnormality. Relative to the relation between structural changes and psychiatric symptoms, structural changes of the temporal lobe areas were related with the positive and general symptoms, while those of the basal ganglia were related with the negative symptoms.