• Journal of Pharmaceutical Investigation
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• v.25 no.3
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• pp.7-20
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• 1995

Taurine, a ${\beta}-amino$ acid, plays an important role as a neuromodulator and is necessary for the normal development of the brain. Since de novo synthesis of taurine in the brain is minimal and in vivo studies suggest that taurine dose not cross the blood-brain barrier, we examined whether the choroid plexus, the blood-cerebrospinal fluid (CSF) barrier, plays a role in taurine transport in the central nervous system. The uptake of $[^3H]-taurine$ into ATP depleted choroid plexus from rabbit was substantially greater in the presence of an inwardly directed $Na^+$ gradient taurine accumulation was negligible. A transient in side-negative potential gradient enhanced the $Na^+-driven$ uptake of taurine into the tissue slices, suggesting that the transport process is electrogenic, $Na^+-driven$ taurine uptake was saturable with an estimated $V_{max}$ of $111\;{\pm}\;20.2\;nmole/g/15\;min$ and a $K_M\;of\;99.8{\pm}29.9\;{\mu}M$. The estimated coupling ratio of $Na^+$ and taurine was $1.80\;{\pm}\;0.122.$ $Na^+-dependent$ taurine uptake was significantly inhibited by ${\beta}-amino$ acids, but not by ${\alpha}-amino$ acids, indicating that the transporter is selective for ${\beta}-amino$ acids. Since it is known that the physiological concentration of taurine in the CSF is lower than that in the plasma, the active transport system we characterized may face the brush border (i.e., CSF facing) side of the choroid plexus and actively transport taurine out of the CSF. Therefore, we examined in vivo elimination of taurine from the CSF in the rat to determine whether elimination kinetics of taurine from the CSF is consistent with the in vitro study. Using a stereotaxic device, cannulaes were placed into the lateral ventricle and the cisterna magna of the rat. Radio-labelled taurine and inulin (a marker of CSF flow) were injected into the lateral ventricle, and the concentrations of the labelled compounds in the CSF were monitored for upto 3 hrs in the cisterna magna. The apparent clearance of taurine from CSF was greater than the estimated CSF flow (p<0.005) indicating that there is a clearance process in addition to the CSF flow. Taurine distribution into the choroid plexus was at least 10 fold higher than that found in other brain areas (e. g., cerebellum, olfactory bulb and cortex). When unlabelled taurine was co-administered with radio-labelled taurine, the apparent clearance of taurine was reduced (p<0.0l), suggesting a saturable disposition of taurine from CSF. Distribution of taurine into the choroid plexus, cerebellum, olfactory bulb and cortex was similarly diminished, indicating that the saturable uptake of taurine into these tissues is responsible for the non-linear disposition. A pharmacokinetic model involving first order elimination and saturable distribution described these data adequately. The Michaelis-Menten rate constant estimated from in vivo elimination study is similar to that obtained in the in vitro uptake experiment. Collectively, our results demonstrate that taurine is transported in the choroid plexus via a $Na^+-dependent,saturable$ and apparently ${\beta}-amino$ acid selective mechanism. This process may be functionally relevant to taurine homeostasis in the brain.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.28 no.4
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• pp.383-391
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• 1995

In order to find out the distribution of neuropeptide Y (NPY) recently known as the gonadotropin (GtH) stimulation neurohormone in the brain tissues of marine teleost, detection and localization of NPY like substance in brain of two rockfish species, Sebastes oblongus and S. schlekeli were done by immunohistochemisty. Distribution of GtH cells in hypophysis were also observed by aldehyde fuchsin (AF)-fast green-orange G stain to compare with gonadal phases of the rockfish species. NPY immunoreactive cells were detected in olfactory bulb, telencephalon and mesencephalon of the brain, and NPY immunoreactive fibers were distributed not only in olfactory bulb, telencephalon and mesencephalon but also in optic nerve, hypothalamus and optic tectum. Regardless of ovarian maturation in two rockfish species, NPY immunoreactive fibers were observed in the neurohypophysis adjacent to the AF negative cells in the rostral pars distalis of hypophysis in both species. Moreover, the fibers were distributed in the rostral and proximal pars distalis near to the GtH cells of the hypophysis in both species possessing the growing or mature oocytes. Slight AF stainable GtH cells were detected in hypophysis of two species before parturition (S. oblongus) and in mature stage (S. schlegeli), but AF stainability of the cells in the proximal pars distalis after parturition was more increased than that of the cells Tn mature stage or before parturition. The size and nucleus diameter of GtH cells in S. oblongus and S. schlegeli before parturition were significantly bigger than those of GtH cells in individuals after parturiton (S. oblongus) or with resting ovary (S. schlegeli) (P<0.01).

• Korean Journal of Radiology
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• v.22 no.11
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• pp.1875-1885
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• 2021

Objective: Central nervous system involvement in coronavirus disease 2019 (COVID-19) has been increasingly reported. We performed a systematic review and meta-analysis to evaluate the incidence of radiologically demonstrated neurologic complications and detailed neuroimaging findings associated with COVID-19. Materials and Methods: A systematic literature search of MEDLINE/PubMed and EMBASE databases was performed up to September 17, 2020, and studies evaluating neuroimaging findings of COVID-19 using brain CT or MRI were included. Several cohort-based outcomes, including the proportion of patients with abnormal neuroimaging findings related to COVID-19 were evaluated. The proportion of patients showing specific neuroimaging findings was also assessed. Subgroup analyses were also conducted focusing on critically ill COVID-19 patients and results from studies that used MRI as the only imaging modality. Results: A total of 1394 COVID-19 patients who underwent neuroimaging from 17 studies were included; among them, 3.4% of the patients demonstrated COVID-19-related neuroimaging findings. Olfactory bulb abnormalities were the most commonly observed (23.1%). The predominant cerebral neuroimaging finding was white matter abnormality (17.6%), followed by acute/subacute ischemic infarction (16.0%), and encephalopathy (13.0%). Significantly more critically ill patients had COVID-19-related neuroimaging findings than other patients (9.1% vs. 1.6%; p = 0.029). The type of imaging modality used did not significantly affect the proportion of COVID-19-related neuroimaging findings. Conclusion: Abnormal neuroimaging findings were occasionally observed in COVID-19 patients. Olfactory bulb abnormalities were the most commonly observed finding. Critically ill patients showed abnormal neuroimaging findings more frequently than the other patient groups. White matter abnormalities, ischemic infarctions, and encephalopathies were the common cerebral neuroimaging findings.

• Animal cells and systems
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• v.15 no.4
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• pp.268-273
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• 2011

Transgenic mice expressing green fluorescent protein (GFP) under the control of human glial fibrillary acidic protein promoter (hGFAP) have been utilized for in vivo labeling of astrocytes. Although it has been considered that virtually all astrocytes express GFP in this transgenic mouse, we found that different subsets of GFAP-expressing astrocytes express considerably different levels of GFP in the adult brain. Astrocytes in the spinal cord, the molecular layer of thecerebellum, meninges, white matter, corpus callosum and blood vessels exhibited strong GFP, whereas subsets of astrocytes associated with granule cells in the cerebellum and dentate gyrus did not or only marginally exhibited GFP. We also found that a small subset of GFP-expressing cells in the periglomeruli of the olfactory bulb did not express GFAP immunoreactivity. Collectively, these results suggest that human GFAP promoter-derived GFP expression does not faithfully recapitulate the endogenous GFAP expression in mice, suggesting that upstream regulatory mechanisms controlling GFAP transcription are different in different populations of astrocytes, and may reflect the functional diversity of astrocytes.

• Environmental Analysis Health and Toxicology
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• v.18 no.2
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• pp.155-163
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• 2003

Fluoranthene, a common polycyclicaromatic hydrocarbon (PAH), exhibits phototoxicity which may affect aquatic organisms. The eventual goal of this study is to develop a biomarker of Japanese medaka (Oryzias latipes) used in monitoring hazardous chemicals in the ecosystem. In this study we investigated neural toxicity of fluoranthene in Japanese medaka (Oryzias latipes) along with comparative analysis of corresponding behavioral response. The untreated individuals shooed normal behavioral characteristics (i. e., smooth and linear movements). The treated fish, however, showed stopping and abrupt change of orientation (100 ppb), and severely reduced locomotive activity and enhanced surfacing activity (1,000 ppb). Treatment of the medaka fish with fluoranthene caused a significant suppresson of acetycholine esterase (AChE) activities in the body portion but not in the head portion. When fish were exposed to 1,000 ppb of fluoranthene for 24 hr, the body AChE activities decreased from 126.${\pm}$31.89 (nmoles substrate hydrolyzed per min per mg protein) to 49.51${\pm}$11.99. Expressions of tyrosine hydroxylase (TH) protein in the different organs from both head and body portions were comparatively analyzed using an immunohistochemical technique. Five organs of the medaka fish showing a strong TH protein expression were the olfactory bulb, hypothalamus, optic lobe, pons and myelencephalon regions. This study provides molecular and neurobehavioral bases of a biomonitoring system for toxic chemicals using fish as a model organism.

• The Korean Journal of Pharmacology
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• v.20 no.1 s.34
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• pp.33-39
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• 1984

The present study was undertaken to elucidate the chracteristics in behavioral changes of chronic doses of methamphetamine on open-field activity in rats. On the other hand, the nucleus accumbens septi(NAB), one of the major areas containing mesolimbic dopaminergic terminals, has been considered to be an important site of action for dopaminergic agonists. Therefore, it also designed to investigated influence of NAB lesions. on behavioral effects of chronic-methamphetamine. Caudal and rostral areas of NAB(cr-NAB) were lesioned by applying DC of 3.0 mA for 15 sec., simultaneously. The results were as follows: 1) The rats exhibited hyperactivity after chronic administration of methamphetamine 2) The cr-NAB-lesioned rats showed a significant increase in locomotor activity only at 2 days after NAB lesions 3) Methamphetamine-induced hyperactivity was significantly decreased in the NAB-lesioned rats, and stereotyped behavior was induced instead by the drug. 4) Dopamine content of striatum was significantly decreased and serotonin content of olfactory bulb was significantly increased in NAB-lesioned rats. These results suggest that NAB plays an important role in locomotor activity and methamphetamine-induced hyperactivity.

• Korean Journal of Veterinary Research
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• v.35 no.2
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• pp.369-374
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• 1995

Aujeszky's disease virus(ADV) was inoculated intranasally into the Korean native goats to investigate pathological findings and pathogenesis of ADV infection by using of histological and immunohistochemical methods and in situ hybridization(ISH). Clinical signs of salvation, pyrexia, pruritus and staggering were followed by death with five days after inoculation, Pathoanatomical findings were edema of the lung and the urinary bladder with hemorrhage and congestion, petechial hemorrhages on the endo-and epicardium, renal congestion, moderate splenomegaly and cystic edema. Main microsocpic lesions observed in all infected goats were confined to the CNS and charcterized by perivascular cuffing with lymphocytes and macrophages, focal gliosis, neuronal degeneration and necrosis, and intranuclear inclusion bodies in the neurons and glial cells. Positive reactions to ADV were detected more frequently in the nuclei than in the cytoplasms of infected nerve cells in the CNS by immunohistochemistry and ISH. Frequenctly localized sites of ADV in the CNS were olfactory bulb, prietal cortex, callosal sulcus and corpus callosum. Positive reactions were also detected in the tonsillar epithelium, and alveolar macrophage and sloughed epithelium of the lung.

• Proceedings of the KIEE Conference
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• 2002.11a
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• pp.257-259
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• 2002

In investigating the characteristics of a neural network, the use of planar microelectrode array shows several advantages over normal intracellular recording[1]. A transparent indium tin oxide(ITO) multi-electrode array(MEA) was fabricated and its top surface was insulated with photodefinable polyimide(HD-8001) except the exposed area for interfacing between the ITO electrodes and the neuronal cells. The exposed ITO electrodes were platinized in order to reduce the impedance between the electrodes and electrolyte. The one-minute platinization with $0.99nA/{\mu}m^2$ current density reduced the average impedance of the electrodes from $2.5M\Omega\;to\;90k\Omega$ at 1kHz in normal ringer solution. Cardiac cells were cultured on this MEA as a pilot study before neuron culture. The signals detected by the platinized electrodes had larger amplitudes and improved signal to noise ratio(SNR) compared to non-platinized electrodes. It is clear that microelectrodes need to have lower impedance to make reliable extracellular recordings, and thus platinization is essential part of MEA fabrication. Burst spike of cultured olfactory bulb was also detected with the MEA having platinized electrodes.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.32 no.3
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• pp.266-270
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• 1999

Two forms of gonadotropin releasing hormone (GnRH) are identified in the brain of adult mature spotted sea bass (Lateolabrax sp.) by immunohistochemical methods. Salmon GnRH immunoreactive (sGnRH-ir) cell bodies were distributed in the olfactory bulb, ventral telencephalon and preoptic region. Immunoreactive fibers were observed in the vicinity of the brain including the olfactory bulbs, the telencephalon, the optic nerve, the optic tectum, the cerebellum, the medulla oblongata and rostral spinal cord. In most cases, these fibers did not form well defined bundles. However, there was a clear continuum of immunoreactive fibers, extending from the olfactory bulbs to the pituitary. cGnRH-II-ir cell bodies were only found in olfactory bulbs. However, the distribution of cGnRH-II-ir fibers was basically similar to that of sGnRH-ir fibers except for the absence of their continuity between the olfactory bulbs and the pituitary. These data suggest that sGnRH and cGnRH-II are endogenous peptides and indicate the presence of multiple neuroendocrine functions in the brain of the spotted sea bass. It seems that sGnRH not only regulates GTH secretion but also functions as a neurotransmitter, whereas cGnRH-II functions only as a neurotransmitter.

• Environmental Analysis Health and Toxicology
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• v.18 no.2
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• pp.145-153
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• 2003

The goal of this study is to develop a biomarker used in monitoring abnormal behaviors of Japanese medaka (Oryzias latipes) as a model organism caused by hazardous chemicals. Japanese medaka was treated by copper of appropriate sublethal concentrations after starvation for 48 hr. The untreated individuals showed common behavioral characteristics (i.e. , smooth and linear movements). Locomotive activity of the fish was monitored using an image processing and automatic data acquisition system. When treated with copper (100 ppb), the fish showed shaking patterns more frequently. As the concentration of copper increased to 1,000 ppb, activity decreated, and the fish showed an erratic movement. Fish were exposed to copper at various concentrations (0,100 and 1,000 ppb) for 24 hrs, and acetylcholine esterase (AChE) activity was observed. When fish were exposed to 1,000 ppb of copper, the body AChE activities appeared to decrease but the head AChE activities showed little change. Expressions of tyrosine hydroxylase (TH) protein in the different organs from both head (brain) and body (kidney) portions affected by the copper treatment were analyzed using immunohistochemical technique compared with control. Five organs of the fish (olfactory bulb, hyothalamus, optic lobe, pons and myelencephalon regions) showed a relatively strong TH protein expression in the control experiment. A differential expression of TH, however, was observed in the treatment (100 ppb and 1,000 ppb). The treatment (1,000 ppb) significantly suppressed TH protein production in the brain regions. In kidney, however, the same treatment caused little suppression compared with the control. Copper appeared to be less effective in suppression of TH than diazinon, a known TH suppressor. It was concluded that TH could be used at a potential biomarker to monitor the acute copper toxicity in Japanese medaka.