Biomedical subjects

Kyeung Min Joo

Publications and source records attributed to Kyeung Min Joo.

At least 19 recordsLinked to original sources

PubMed2006

Age-related changes in glycogen synthase kinase 3beta (GSK3beta) immunoreactivity in the central nervous system of rats.

Although glycogen synthase kinase 3beta (GSK3beta) is emerging as a prominent drug target in the treatment of neurodegenerative diseases such as Alzheimer's disease (AD) and stroke, very little is known about age-related changes in GSK3beta expression and GSK3beta phosphorylation. Therefore, we examined age-related changes in immunoreactivities for GSK3beta and phosphorylated GSK3beta (pGSK3beta) in the central nervous system. In aged rats, there were significant increases in GSK3beta immunoreactivity in the cell bodies and processes of pyramidal cells in most cortical regions. GSK3beta immunoreactivity was also significantly increased in the pyramidal layer of CA1-3 regions, and the granule cell layer of dentate gyrus. Age-related increases were prominent in lateral septal nuclei, compared to the medial septal nuclei. Interestingly, both GSK3beta and pGSK3beta was increased in the prefrontal cortex, while GSK3beta and pGSK3beta was differentially localized in the cerebellar cortex. The first demonstration of age-related alterations in immunoreactivities for GSK3beta and pGSK3beta in the basal forebrain area and cholinergic projection targets may provide useful data for investigating the pathogenesis of age-related neurodegenerative diseases including AD.

Aging↗

PubMed2005

Reduced immunoreactivities of a vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide receptor (VPAC1 receptor) in the cerebral cortex, hippocampal region, and amygdala of aged rats.

In this study, we examined expressional changes of VPAC1 receptor in aged rat brains using an immunohistochemical approach and found that its immunoreactivities are significantly reduced in the cerebral cortex, hippocampal region, and amygdala of aged rats. These results suggest that this reduction could underlie aging-associated memory/learning deficits and several other age-induced functional changes in these areas. However, the functional consequences of these down-regulations require further elucidation.

Aging↗

PubMed2005

Immunohistochemical study on the distribution of phosphorylated extracellular signal-regulated kinase (ERK) in the central nervous system of SOD1G93A transgenic mice.

In the present study, we performed immunohistochemical studies to investigate the changes of phosphorylated extracellular signal-regulated kinases (pERK) in the central nervous system of SOD1(G93A) transgenic mice. In symptomatic transgenic mice, pERK-immunoreactive astrocytes were detected in the spinal cord, brainstem, central gray and cerebellar nuclei. In contrast to symptomatic mice, no pERK-immunoreactive astrocytes were observed in any brain region of wtSOD1 and presymptomatic mice, and the number and intensity of stained neurons were not different at the age of 8 weeks and 13 weeks. Interestingly, region-specific alterations in pERK immunoreactivity were observed in the hippocampal region and cerebellum. These results provide the first evidence that pERK-immunoreactive astrocytes were found in the CNS of SOD1(G93A) transgenic mice after clinical symptoms, showing a possible consequence of the pathological process of ALS. This study has also demonstrated that pERK increases in the hippocampus and cerebellum, suggesting a role of pERK in an abnormality of cognitive and/or motor function in ALS, respectively. However, the mechanisms underlying the increased immunoreactivity for pERK and the functional implications require elucidation.

Amyotrophic Lateral Sclerosis↗

PubMed2005

Decreased expression of calretinin in the cerebral cortex and hippocampus of SOD1G93A transgenic mice.

In the present study, we investigated the changes of calretinin (CR) expression in the central nervous system of SOD1G93A transgenic mice as an in vivo model of amyotrophic lateral sclerosis (ALS). In wild-type SOD1 (wtSOD1) transgenic mice, many CR-immunoreactive neurons were found in all cortical regions. In the cerebral cortex of SOD1G93A transgenic mice, the number and staining intensity of CR-positive neurons were decreased. In the hippocampal formation, layer-specific alterations in the staining intensity of CR-immunoreactive neurons were observed in the CA1-3 areas and dentate gyrus. In wtSOD1 transgenic mice, CR-immunoreactive neurons with long processes were found in the stratum oriens and stratum radiatum of CA1-3 areas, and heavily stained band-like molecular layer was prominent in the dentate gyrus. CR immunoreactivity was decreased in each layer of CA1-3 areas and dentate gyrus of SOD1G93A transgenic mice. The first demonstration of decreased immunoreactivity for CR in the cerebral cortex and hippocampus of SOD1G93A transgenic mice may provide insights into the pathogenesis of motor neuron degeneration in human ALS although further quantitative studies are needed.

Animals↗

PubMed2005

Immunohistochemical study on the distribution of the voltage-gated potassium channels in the gerbil cerebellum.

Although there have been many studies on the regional distribution of Kv channels in the rat and mouse cerebellum, there are no reports about Kv channel distribution in the gerbil, which is used as an ischemia animal model. Therefore, we aimed to investigate differences in the spatial patterning of Kv channel alpha-subunit isoforms in the gerbil cerebellum. The greatest concentration of Kv1.2 was found in the basket cell axon plexus and terminal regions around the Purkinje cells. Kv1.1 immunoreactivity was also concentrated in this area although the staining intensity was relatively lower. Both Purkinje cell layer and granular layer were intensely stained with anti-Kv1.3 and Kv1.6 antibodies, whereas immunoreactivities for Kv1.4 and Kv1.5 were detected in the Purkinje cell bodies with much lower intensity in the molecular and granular layers. In the cerebellar nuclei, the cell bodies of cerebellar output neurons showed strong immunoreactivities for Kv1.2, Kv1.4, and Kv1.6 with moderate staining for Kv1.3 and Kv1.5 in the cell bodies. This study on the differential localization patterns of Kv1 channel subunits in the gerbil cerebellum may provide helpful guidelines for correlating current types with particular channels and useful data for the future investigations on the pathological conditions such as ischemia and epilepsy.

Animals↗

PubMed2005

Glial fibrillary acidic protein is expressed in the aged rat olfactory epithelium.

CONCLUSION: Our findings suggest that the aging process induces changes in the phenotype of olfactory supporting cells in the rat. OBJECTIVE: To investigate age-related changes in the expression of astroglial intermediate filament proteins in the olfactory supporting cells of the rat. MATERIAL AND METHODS: The expression of nestin and glial fibrillary acidic protein (GFAP) in the olfactory epithelium (OE) of young (3 months) and aged (25 months) Sprague-Dawley rats was compared using Western blotting and immunohistochemistry. RESULTS: Western blot analysis showed nestin expression only in the young OE, whereas GFAP was detected only in the aged OE. Immunohistochemistry showed that GFAP was localized in the olfactory supporting cells of the aged OE, with regional differences.

Age Factors↗

PubMed2005

Age-related changes in the distribution of Kv1.1 and Kv3.1 in rat cochlear nuclei.

OBJECTIVES: To identify age-related changes in voltage-gated K(+) (Kv) channels that contribute to temporal processing in neurons of the central auditory system, we investigated the distribution of Kv1.1 and Kv3.1 in the auditory brainstem of adult and aged rats. METHODS: Immunohistochemistry was performed in accordance with the free-floating method described earlier. RESULTS: Among the auditory nuclei, only the posterior ventral cochlear nucleus (PVCN) showed age-related changes. Kv1.1 immunoreactivity was increased in the octopus cell bodies, while the staining intensity was significantly decreased in the neuropil. Image analysis demonstrated the specific increase in Kv1.1 immunoreactivity in aged cochlear nucleus neurons although the mean density of the entire selection was significantly decreased. In contrast, the number of Kv1.1-immunoreactive neurons was not significantly different between control and aged groups. The immunoreactivity for Kv3.1 was decreased in the octopus cells and neuropil of aged PVCN, which was confirmed by image analysis. The number of Kv3.1-positive cells was also significantly decreased in aged PVCN. DISCUSSION: This study may provide useful data to compare age-related changes in Kv1.1 and Kv3.1 with known physiological properties of auditory neurons.

Age Factors↗

PubMed2004

Immunohistochemical study of the distribution of neuronal voltage-gated calcium channels in the nNOS knock-out mouse cerebellum.

Nitric oxide (NO) participates in synaptic plasticity, neuronal development, and apoptosis. The involvement of NO and ionic calcium in synaptic plasticity imply that NO may exert an effect on Ca2+ channels. Therefore, we investigated changes in the expressions of calcium channel subunits (Cav1.2/alpha1C, Cav1.3/alpha(1D), Cav2.1/alpha1A, and Cav2.2/alpha1B) in nNOS knock-out (-/-) (nNOS((-/-))) mouse cerebellum using an immunohistochemical approach. We found that the immunoreactivities of the Cav1.2 and Cav1.3 subunits were reduced in the cell bodies of Purkinje cells in these mice and that the signal of the Cav1.2 subunit in neurons and of the Cav1.3 subunit in the neuropils of nNOS((-/-)) mice cerebellar nuclei were significantly down-regulated. We show, for the first time, that prolonged NO deficiency in the cerebellum may affect calcium channel protein expressions, especially, of the Cav1.2 and Cav1.3 subunits.

Animals↗

PubMed2004

Region-specific alterations in insulin-like growth factor-I receptor in the central nervous system of nNOS knockout mice.

In the present study, we investigated layer-specific changes in insulin-like growth factor-I (IGF-I) receptor localization in the cerebral cortex, hippocampus and cerebellum of neuronal nitric oxide synthase knockout (nNOS-/-) mice using immunohistochemistry. In the cerebral cortex of control mice, moderately stained cells were seen through the layers II-VI in several cortical regions. In nNOS-/- mice, there was a significant decrease in IGF-I receptor immunoreactivity in the same cortical regions. In the hippocampus of control mice, a distinct immunoreactivity pattern was observed in the CA1-3 areas and dentate gyrus. The immunoreactivity for IGF-I receptor was differentially decreased in each layer in nNOS-/- mice. In nNOS-/- cerebellum, IGF-I receptor immunoreactivity was also significantly decreased in each layer of cerebellar cortex and cerebellar nuclei. To clarify whether decreased expression of IGF-I receptor in nNOS-/- mice was specific, the expression of other receptors for IGF-I was also evaluated. Receptor tyrosine kinase type A (TrkA receptor) and TrkB receptor were differentially decreased in each layer of the hippocampus or cerebellum of nNOS-/- mice. Although further studies of functional features of IGF-I systems in the nNOS-/- mice are required, our first morphological data may provide insights into NO-induced changes in trophic support as well as basic knowledge required for the study of NO-associated neurological diseases.

Animals↗

PubMed2004

Distribution of vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide receptors (VPAC1, VPAC2, and PAC1 receptor) in the rat brain.

To examine the distributions of VIP/PACAP receptors (VPAC1, VPAC2, and PAC1 receptors) in the brain and to identify the cell types that express these receptors, we performed immunohistochemistry and double immunofluorescence in the rat brain with specific antibodies. The immunohistochemistry revealed that the receptors had distinctive, complementary, and overlapping distribution patterns. High levels of the VPAC1 receptor were expressed in the cerebral cortex, hippocampal formation, deep cerebellar nuclei, thalamus, hypothalamus, and brainstem. The VPAC2 receptors were concentrated in the cerebral cortex, hippocampal formation, amygdalar regions, cerebellar cortex, deep cerebellar nuclei, hypothalamus, and brainstem. On the other hand, the PAC1 receptors had a more restricted distribution pattern in the brain, and high levels of the PAC1 receptors were confined to the cerebellar cortex, deep cerebellar nuclei, epithalamus, hypothalamus, brainstem, and white matter of many brain regions. Also, many fibers expressing the PAC1 receptors were observed in various areas, i.e., the thalamus, hypothalamus, and brainstem. The double immunofluorescence showed that the VIP/PACAP receptors were confined to the neuroglia as well as the neurons. All three types of the VIP/PACAP receptors were expressed in the astrocytes, and the PAC1 receptors were also expressed in the oligodendrocytes. These findings indicate that VIP and PACAP exert their functions through their receptors in specific locations in different combinations. We hope that this first demonstration of the distributions of the VIP/PACAP receptors provides data useful in the investigation of the mechanisms of the many functions of VIP and PACAP in the brain, which require further elucidation.

Aging↗

PubMed2004

Age-related changes in erythropoietin immunoreactivity in the cerebral cortex and hippocampus of rats.

Although oxidative stress may influence the fluid properties of blood, resulting in a potential decrement in blood flow and oxygen delivery to the brain during aging, very little is known about age-related changes in Epo expression. Therefore, we examined age-related changes in Epo expression in the cerebral cortex and hippocampus with an immunohistochemical technique. In aged rats, there was a significant decrease in Epo immunoreactivity in the pyramidal cells in the cortical regions. In the hippocampus of adult rats, a distinct immunoreactivity pattern was observed in the CA1-3 areas and dentate gyrus. In aged hippocampus, Epo immunoreactivity was significantly deceased in the pyramidal layer of CA1 regions, and the granule cell layer of dentate gyrus. It was noted that there was distinct pattern of Epo immunoreactivity in the pyramidal layer of CA2-CA3 region of aged rats. Epo immunoreactivity was relatively strong, but was observed only in the periphery of the cytoplasm. The first demonstration of age-related decreases in Epo expression in the cerebral cortex and hippocampus may provide useful data for investigating the pathogenesis of age-related neurodegenerative diseases, suggesting that age-related decreases in Epo may contribute to degenerative events following age-related decreases in brain flow and oxygen supply.

Aging↗

PubMed2004

Enhanced expression of erythropoietin in the central nervous system of SOD1(G93A) transgenic mice.

In the present study, we investigated the changes of erythropoietin (Epo) expression in the central nervous system (CNS) of SOD1(G93A) transgenic mice as an in vivo model of amyotrophic lateral sclerosis (ALS). In wild-type SOD1 (wtSOD1) transgenic mice, little immunoreactivity was found in all cortical regions. In the cerebral cortex of symptomatic SOD1(G93A) transgenic mice, there was a significant increase in Epo immunoreactivity. In the hippocampal formation, layer-specific alterations in the staining intensity were observed in the CA1-3 areas and dentate gyrus. Epo immunoreactivity was significantly increased in the midbrain, cerebellar cortex and brainstem of SOD1(G93A) transgenic mice. On the contrary, Epo immunoreactivity was moderately stained in the spinal cord and was not different between wtSOD1 and SOD1(G93A) transgenic mice at the age of 8 weeks, 13 weeks and 18 weeks. In the staining of Epo receptor (EpoR), the changing pattern was similar with that of Epo in the spinal cord and hippocampal formation in wtSOD1 and SOD1(G93A) transgenic mice. Although further studies of functional features of Epo in ALS are needed, the first demonstration of increased immunoreactivity for Epo in the CNS of SOD1(G93A) transgenic mice may provide initial insights into the development of interventional strategies to alleviate motor neuron degeneration in human ALS.

Animals↗

PubMed2004

Postnatal development and age-related changes in the distribution of nitric oxide synthase-immunoreactive neurons in the visual system of rats.

We have determined postnatal development and age-related changes in the distribution of neuronal nitric oxide synthase (nNOS) in the visual system including superior colliculus (SC), dorsal nucleus of lateral geniculate body (dLGB) and visual cortex of rats. In SC, the number and intensity of immunoreactive cells were increased until postnatal day 21 (P21), and were comparably decreased during the following days. Both neurons and neuropil were intensely stained in dLGB at P21, and the staining intensity was decreased in aged rats. The number of nNOS-immunoreactive cells was increased from P7 to P28 and was decreased in aged rats. The first demonstration of different staining patterns in SC, dLGB and visual cortex during the postnatal days and aging suggests that NO may mediate both postnatal refinement and age-associated visual deficits in some brain regions.

Aging↗

PubMed2004

Reactive astrocytes express PARP in the central nervous system of SOD(G93A) transgenic mice.

In the present study, we used the transgenic mice expressing a human Cu/Zn SOD mutation (SOD1(G93A)) as an in vivo model of amyotrophic lateral sclerosis (ALS) and performed immunohistochemical studies to investigate the changes of poly(ADP-ribose) polymerase (PARP) in the central nervous system. In the spinal cord of symptomatic transgenic mice, immunohistochemistry showed intensely stained PARP-immunoreactive glial cells with the appearance of astrocytes, which were confirmed as astrocytes by double-immunofluorescences. In the brainstem and cerebellum, PARP-immunoreactive astrocytes were observed in the medullary and pontine reticular formation, hypoglossal nucleus, vestibular nucleus, cochlear nucleus and cerebellar nuclei. On the contrary, no PARP-immunoreactive glial cells were observed in control mice although PARP-immunoreactive motor neurons were found. In presymptomatic transgenic mice, a few moderately stained neurons were observed, whereas PARP-immunoreactive astrocytes were not detected. The present study provides the first evidence that PARP-immunoreactive astrocytes were found in the central nervous system of symptomatic SOD1(G93A) transgenic mice, suggesting that reactive astrocytes may play an important role in the pathogenesis and progress of ALS.

Animals↗

PubMed2004

Region-specific alterations of neuronal nitric oxide synthase (nNOS) expression in the amygdala of the aged rats.

Although many amygdalar functions are altered by aging, little is known about their mechanisms. As these functions are related with nitric oxide (NO), we examined neuronal nitric oxide synthase (nNOS) expression in the amygdala of the aged rats via immunohistochemical technique. We found that nNOS immunoreactive neurons are decreased in almost all amygdalar areas of the aged rats, while nNOS immunoreactivity of the neuropil is significantly increased in the amygdalar nuclei related with main and accessory olfactory system. These suggest altered levels of NO might provide region-specific mechanisms of many physiological and behavioral deficits of the amygdala developed by aging. However, exact effects of these changes require further elucidation.

Aging↗

PubMed2003

Immunohistochemical study on the distribution of insulin-like growth factor I (IGF-I) receptor in the central nervous system of SOD1(G93A) mutant transgenic mice.

In the present study, we used the SOD1(G93A) mutant transgenic mice as an in vivo model of ALS and performed immunohistochemical studies to investigate the changes of insulin-like growth factor I (IGF-I) receptor in the central nervous system. IGF-I receptor-immunoreactive astrocytes were detected in the spinal cord, brainstem, central gray and cerebellar nuclei of SOD1(G93A) transgenic mice. In contrast to transgenic mice, no IGF-I receptor-immunoreactive astrocytes were observed in any brain region of wtSOD1 transgenic mice although a few moderately stained neurons were observed. In the hippocampal formation of SOD1(G93A) transgenic mice, IGF-I receptor immunoreactivity was increased in the pyramidal cells of the CA1-3 regions and granule cells of the dentate gyrus. The present study provides the first evidence that IGF-I receptor immunoreactivity was increased in reactive astrocytes in the central nervous system of SOD(G93A) transgenic mice, suggesting that reactive astrocytes may play an important role in the pathogenesis and progress of ALS. The mechanisms underlying the increased immunoreactivity for IGF-I receptor, and the functional implications of these increases, require elucidation.

Amyotrophic Lateral Sclerosis↗

PubMed2003

Immunohistochemical study on the distribution of MnSOD in the central nervous system of the transgenic mice expressing a human Cu/Zn SOD mutation.

In the present study, we used the SOD1(G93A) mutant transgenic mice as an animal model of amyotrophic lateral sclerosis (ALS) and performed immunohistochemical studies to investigate the changes of MnSOD in the central nervous system of transgenic mice at the age of 8, 13, and 18 weeks. In the spinal cord of wild-type SOD1 (wtSOD1) and SOD1(G93A) transgenic mice, MnSOD-immunoreactive neurons were distributed mainly in the anterior horn, although they were also observed in the posterior horn. The staining intensity of MnSOD was significantly increased in the spinal cord of SOD1(G93A) transgenic mice at presymptomatic and symptomatic stage. In the brainstem of symptomatic SOD1(G93A) transgenic mice, significantly increased immunoreactivity for MnSOD was observed in abducens nucleus, facial nucleus, dorsal motor nucleus of vagus, hypoglossal nucleus, medullary and pontine reticular formation, superior and inferior olivary nucleus, and cochlear nucleus. The present study provides the first evidence that MnSOD immunoreactivity was increased in the central nervous system of SOD(G93A) transgenic mice, suggesting that mitochondria may play an important role in the pathogenesis and progress of ALS. The mechanisms underlying the increased immunoreactivity for MnSOD, and the functional implications of these increases, require elucidation.

Amyotrophic Lateral Sclerosis↗

PubMed2003

Vasoactive intestinal peptide (VIP) and VIP mRNA decrease in the cerebral cortex of nNOS knock-out(-/-) mice.

Although there is much evidence showing that NO regulates the release of VIP in several areas, there is no report about the influence of NO on VIP in the cerebral cortex. We therefore examined changes in VIP expression in the cerebral cortex of nNOS knock-out(-/-) mice using immunohistochemistry and in situ hybridization. The nNOS((-/-)) mice had significantly fewer VIP-immunoreactive neurons than the control mice and the VIP mRNA as well as the VIP-immunoreactivity of the individual neuron was decreased in the nNOS((-/-)) mice. The first demonstration of decrease in VIP expression in the cerebral cortex of nNOS((-/-)) mice may provide useful data for investigating the relation between NO and VIP in the cerebral cortex and the mechanisms of many functions of these two neurotransmitters.

Animals↗