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Biomedical subjects

J H Son

Publications and source records attributed to J H Son.

At least 19 recordsLinked to original sources
PubMed2002

Quantification of digesta flow into the caeca.

1. A caecal intubation technique was developed to determine the amount of digesta that enters the caeca of fed and feed-deprived chickens. 2. Dry matter intakes per day for control and caecostomised chickens were not significantly different. 3. For fed and feed-deprived roosters, water intake was significantly increased by caecostomy in control birds and was significantly increased by feeding. 4. Amount of caecal dry matter excretion was significantly increased by feeding, but no difference in caecal water excretion was observed. 5. The ratio of caecal excretion (caecal/total excretion) of dry matter and water tended to decrease in response to feeding. 6. It is concluded that dry matter entry into the caeca represents 18% or 25% of the total dry matter excretion in fed or feed-deprived birds, respectively. Corresponding values for water entry are 17 and 26%. Therefore, the caeca play an important role in water balance.

Animal Feed↗
PubMed2001

Manganese induces endoplasmic reticulum (ER) stress and activates multiple caspases in nigral dopaminergic neuronal cells, SN4741.

Chronic exposure to manganese causes Parkinson's disease (PD)-like clinical symptoms (Neurotoxicology 5 (1984) 13; Arch. Neurol. 46 (1989) 1104; Neurology 56 (2001) 4). Occupational exposure to manganese is proposed as a risk factor in specific cases of idiopathic PD (Neurology 56 (2001) 8). We have investigated the mechanism of manganese neurotoxicity in nigral dopaminergic (DA) neurons using the DA cell line, SN4741 (J. Neurosci. 19 (1999) 10). Manganese treatment elicited endoplasmic reticulum (ER) stress responses, such as an increased level of the ER chaperone BiP, and simultaneously activated the ER resident caspase-12. Peak activation of other major initiator caspases-like activities, such as caspase-1, -8 and -9, ensued, resulting in activation of caspase-3-like activity during manganese-induced DA cell death. The neurotoxic cell death induced by manganese was significantly reduced in the Bcl-2-overexpressing DA cell lines. Our findings suggest that manganese-induced neurotoxicity is mediated in part by ER stress and considerably ameliorated by Bcl-2 overexpression in DA cells.

Animals↗
PubMed2001

Phenotypic differentiation during migration of dopaminergic progenitor cells to the olfactory bulb.

A possible source for transplantable neurons in Parkinson's disease are adult olfactory bulb (OB) dopamine (DA) progenitors that originate in the anterior subventricular zone and reach the OB through the rostral migratory stream. We used adult transgenic mice expressing a lacZ reporter directed by an 8.9 kb tyrosine hydroxylase (TH) promoter to investigate the course of DAergic differentiation. Parallel transgene and intrinsic TH mRNA expression occurred during migration of DA interneurons through the mitral and superficial granule cell layers before these cells reached their final periglomerular position. Differential transgene and calcium-calmodulin-dependent protein kinase IV expression distinguished two nonoverlapping populations of interneurons. Transgenic mice carrying a TH8.9kb/lacZ construct with a mutant AP-1 site demonstrated that this element confers OB DA-specific TH gene regulation. These results indicate that DA phenotypic determination is specific to a subset of mobile OB progenitors.

Animals↗
PubMed2001

Dopaminergic cell death induced by MPP(+), oxidant and specific neurotoxicants shares the common molecular mechanism.

Recent etiological study in twins (Tanner et al. 1999) strongly suggests that environmental factors play an important role in typical, non-familial Parkinson's disease (PD), beginning after age 50. Epidemiological risk factor analyses of typical PD cases have identified several neurotoxicants, including MPP(+) (the active metabolite of MPTP), paraquat, dieldrin, manganese and salsolinol. Here, we tested the hypothesis that these neurotoxic agents might induce cell death in our nigral dopaminergic cell line, SN4741 (Son et al. 1999) through a common molecular mechanism. Our initial experiments revealed that treatment with both MPP(+) and the other PD-related neurotoxicants induced apoptotic cell death in SN4741 cells, following initial increases of H(2)O(2)-related ROS activity and subsequent activation of JNK1/2 MAP kinases. Moreover, we have demonstrated that during dopaminergic cell death cascades, MPP(+), the neurotoxicants and an oxidant, H(2)O(2) equally induce the ROS-dependent events. Remarkably, the oxidant treatment alone induced similar sequential molecular events: ROS increase, activation of JNK MAP kinases, activation of the PITSLRE kinase, p110, by both Caspase-1 and Caspase-3-like activities and apoptotic cell death. Pharmacological intervention using the combination of the antioxidant Trolox and a pan-caspase inhibitor Boc-(Asp)-fmk (BAF) exerted significant neuroprotection against ROS-induced dopaminergic cell death. Finally, the high throughput cDNA microarray screening using the current model identified downstream response genes, such as heme oxygenase-1, a constituent of Lewy bodies, that can be the useful biomarkers to monitor the pathological conditions of dopaminergic neurons under neurotoxic insult.

1-Methyl-4-phenylpyridinium↗
PubMed2001

Effects of caecal ligation and colostomy on water intake and excretion in chickens.

1. The effect of caecal ligation and colostomy on water intake and excretion were examined in chickens fed a low-protein diet or a low-protein diet supplemented with urea. 2. When fed a low-protein diet, the water intake and the ratio of water intake to food intake were increased by colostomy (P < 0.05) but not changed further by caecal ligation of colostomised chickens. 3. When fed a low-protein diet supplemented with urea, the amount of water intake and the ratio of water intake to food intake were not changed by either treatment. 4. Total water excretion was much higher in the colostomised plus caeca-ligated chickens than in other 3 groups fed both types of diet (P < 0.05). 5. The amount of faecal water excretion was increased by cecal ligation in colostomised chickens fed either diet (P < 0.01). 6. No effect of any treatment on water balance was observed in chickens fed either diet. 7. It is concluded that the lower intestine plays a useful role in the water economy of chickens fed a low-protein diet or a low-protein diet supplemented with urea.

Animal Feed↗
PubMed2000

The zona pellucida-initiated acrosome reaction: defect due to mutations in the sperm glycine receptor/Cl(-) channel.

The mammalian sperm acrosome reaction (AR) is essential to fertilization, and the egg zona pellucida (ZP) is generally believed to be an in vivo initiator of the fertilizing sperm AR. Previously a neuronal glycine receptor/Cl(-) channel (GlyR) was detected on the plasma membrane of mammalian sperm and earlier pharmacological studies suggested that this receptor/channel is important to the ZP-initiated AR. Here, sperm from mice with mutations in the neuronal GlyR alpha or beta subunits (spasmodic and spastic) were shown to be deficient in their ability to undergo the AR initiated in vitro by glycine or by solubilized ZP from mouse eggs. However, both spontaneous and calcium ionophore (A23187)-initiated AR were unaffected. The ZP-initiated AR in wild-type sperm was maximal after 2 h of capacitation, but capacitation of sperm from spasmodic mice for up to 3 h did not result in significant ZP-initiated AR. Similar results were observed when sperm from wild-type and spastic mice were compared. Testis from mice with the beta subunit mutation contained truncated beta subunit mRNAs. Moreover, a monoclonal antibody against GlyR completely blocked ZP initiation of AR in normal mouse sperm. Our results are consistent with an essential role for the sperm GlyR in the ZP-initiated AR.

Acrosome Reaction↗
PubMed2000

Identification of potential compounds promoting BDNF production in nigral dopaminergic neurons: clinical implication in Parkinson's disease.

Parkinson's disease (PD) is characterized by the selective loss of dopamine (DA) neurons in the substantia nigral brain region. Currently, there is no cure or treatment that prevents such neuronal loss. Brain-derived neurotrophic factor (BDNF) has been found to support the survival of DA neurons in animal models and in primary cell cultures. However, the large molecular size of BDNF, coupled with the blood brain barrier, prevents its delivery to DA neurons to promote cell survival in the PD brain. The nigral DA neurons have the ability to produce BDNF for neuroprotection via either autocrine or paracrine mechanisms. Low mol. wt compounds were tested to see whether they could increase the production of BDNF in the DA neurons. The compounds tested include neurotransmitters, neuropeptides, intracellular signaling agents, known neuroprotective agents and growth factors. Our results demonstrate that salicyclic acid, cGMP analog, okadaic acid, IBMX, dipyridamole and glutamate significantly enhance BDNF production in DA neuronal cells.

Brain-Derived Neurotrophic Factor↗
PubMed2000

Effect of removal of caecal contents on nitrogen utilisation and nitrogen excretion in caecally ligated chickens fed on a low protein diet supplemented with urea.

1. The effect of washing out the caecal contents on nitrogen utilisation and nitrogen excretion were examined in Single Comb White Leghorn cockerels fed on a 50 g/kg protein diet supplemented with urea. 2. Flushing out the caecal contents with saline in caecally ligated chickens produced a significantly increased nitrogen balance and increased nitrogen utilisation (P<0.05). 3. Washing out the caecal contents significantly decreased uric acid excretion but the treatment had no effect on urea and ammonia excretion. 4. Caecal bacterial contents were significantly decreased by caecal ligation and decreased further by washing out the caecal contents. 5. It is concluded that nitrogen metabolism in chickens is affected by possible changes in caecal fermentation produced by preventing substances from urine and digesta from entering the caeca.

Ammonia↗
PubMed2000

Effect of caecectomy on growth, moisture in excreta, gastrointestinal passage time and uric acid excretion in growing chicks.

1. The effect of caecectomy on nitrogen utilisation and excretion was examined in growing chicks fed on a commercial diet. 2. Caecectomy had no significant effect on food intake or body weight gain. 3. Caecectomy caused significantly higher moisture content in excreta (P<0.01). 4. Gastrointestinal passage time of digesta was significantly shorter in caecectomised chicks than in control chicks (P<0.05). 5. Caecectomy tended to improve nitrogen utilisation rate in growing chicks. 6. The treatment significantly decreased uric acid excretion (P<0.01) and excretory uric acid-N/total nitrogen excretion (P<0.01). 7. It is concluded that the effects of caecectomy on nitrogen metabolism in growing chicks are similar to those in adult chickens.

Animals↗
PubMed1999

Neuroprotection and neuronal differentiation studies using substantia nigra dopaminergic cells derived from transgenic mouse embryos.

The major pathological lesion of Parkinson's disease (PD) is the selective cell death of dopaminergic (DA) neurons in substantia nigra (SN). Although the initial cause and subsequent molecular signaling mechanisms leading to DA cell death underlying the PD process remain elusive, brain-derived neurotrophic factor (BDNF) is thought to exert neuroprotective as well as neurotrophic roles for the survival and differentiation of DA neurons in SN. Addressing molecular mechanisms of BDNF action in both primary embryonic mesencephalic cultures and in vivo animal models has been technically difficult because DA neurons in SN are relatively rare and present with many heterogeneous cell populations in midbrain. We have developed and characterized a DA neuronal cell line of embryonic SN origin that is more accessible to molecular analysis and can be used as an in vitro model system for studying SN DA neurons. A clonal SN DA neuronal progenitor cell line SN4741, arrested at an early DA developmental stage, was established from transgenic mouse embryos containing the targeted expression of the thermolabile SV40Tag in SN DA neurons. The phenotypic and morphological differentiation of the SN4741 cells could be manipulated by environmental cues in vitro. Exogenous BDNF treatment produced significant neuroprotection against 1-methyl-4-phenylpyridinium, glutamate, and nitric oxide-induced neurotoxicity in the SN4741 cells. Simultaneous phosphorylation of receptor tyrosine kinase B accompanied the neuroprotection. This SN DA neuronal cell line provides a unique model system to circumvent the limitations associated with primary mesencephalic cultures for the elucidation of molecular mechanisms of BDNF action on DA neurons of the SN.

1-Methyl-4-phenylpyridinium↗
PubMed1999

Altered presynaptic gene expression in transgenic mice producing dopamine in the pineal gland.

Neurotransmitters are known to play an important role in the development of the nervous system. We recently generated transgenic mice that ectopically express tyrosine hydroxylase (TH) and thereby produce dopamine (DA) de novo in pinealocytes of the pineal gland (PG). The transgenic PG also exhibited a dramatic decrease in TH-immunoreactive (IR) fibers putatively arising from the superior cervical ganglion (SCG) (Cho et al. [1996] Proc Natl Acad Sci USA 93:2862-2866). In the current study, however, we found that there was no reduction in the number of fibers immunostained for neurofilament protein or PGP9.5, markers known to be heavily localized in fibers, despite the reduction of TH fiber density. Therefore, we investigated whether the decreased TH-IR fiber density is the consequence of reduced sympathetic innervation, or a decrease in TH expression within innervating fibers. Immunohistochemical analysis comparing control and transgenic PG demonstrated no apparent differences in numbers of NPY- and aromatic-L-amino acid decarboxylase (AADC)-IR fibers, indicating that TH expression is decreased in a normal number of innervating fibers. Furthermore, presynaptic neurons in the transgenic SCG showed abnormal and heterogeneous TH immunoreactivity and reduced TH and norepinephrine transporter (NET) mRNA levels. These results show that ectopic DA production in the PG lowers TH and NET gene expression in the SCG without altering sympathetic innervation to the PG and suggest that the alteration of target neurotransmitter phenotype may influence gene expression of phenotype-specific proteins in projecting neurons.

Animals↗
PubMed1998

Regulation of tyrosine hydroxylase promoter activity by chronic morphine in TH9.0-LacZ transgenic mice.

Levels of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, are known to be upregulated in specific brain regions by chronic administration of drugs of abuse. Chronic morphine administration increases TH levels in the locus coeruleus and ventral tegmental area, whereas chronic cocaine administration increases TH levels in the ventral tegmental area only. While such upregulation of TH has been related to behavioral effects of the drugs, the mechanism underlying these adaptations has remained controversial. To study the possibility that upregulation of TH occurs at the transcriptional level, we investigated the effect of chronic morphine or cocaine treatment on the activity of the TH gene promoter (9.0 kb), coupled to the LacZ reporter gene, in transgenic mice. These TH9.0-LacZ mice have been shown to exhibit correct tissue-specific expression and regulation of the reporter gene. We show here that chronic (but not acute) exposure of the TH9.0-LacZ mice to morphine increases the expression of beta-galactosidase (which is encoded by the LacZ gene) in the locus coeruleus by twofold compared with sham-treated mice. In contrast, beta-galactosidase expression in the ventral tegmental area was decreased 20-25% by chronic morphine and unaffected by chronic cocaine administration. Similar results were obtained after analysis of TH mRNA levels in these brain regions by in situ hybridization. These results suggest that chronic morphine upregulates TH expression via transcriptional mechanisms in the locus coeruleus but by post-transcriptional mechanisms in the ventral tegmental area.

Animals↗
PubMed1998

Differential expression of monoamine oxidase A, serotonin transporter, tyrosine hydroxylase and norepinephrine transporter mRNA by anorexia mutation and food deprivation.

The Anorexia (anx) mutation causes reduced food intake in preweanling mice, resulting in death from starvation within 3-4 weeks. We have found serotonin (5HT) hyperinnervation in the anx brain; altered noradrenergic (NE) innervation may also mediate eating disorders. We examined the expression of synthetic or catabolic monoamine enzyme genes in brainstem nuclei: serotonin transporter (5HTT) and monoamine oxidase A (MAOA) in the raphe nuclei (RN), and MAOA, norepinephrine transporter (NET), and tyrosine hydroxylase (TH) in the locus ceruleus (LC). We compared 3-week old anx with control and 24-h food-deprived wildtype littermates using in situ hybridization to measure mRNA levels by quantitative autoradiography. The anx mutation was correlated with decreased MAOA mRNA in the LC (but not RN), decreased 5HTT mRNA in the RN, and a trend towards lower NET mRNA in the LC. Food deprivation decreased MAOA mRNA in the LC (but not RN), increased TH mRNA in the LC, and did not alter NET or 5HTT mRNA levels. Thus, the effect of the anx mutation on MAOA expression in the LC paralleled the effect of food-deprivation, but the anx mutation and food-deprivation had differential effects on the expression of TH, NET, and 5HTT genes. Decreased 5HTT expression in the anx RN is consistent with upregulation of serotonergic neurotransmission that may accompany 5HT hyperinnervation. Central NE levels or innervation may be altered in anx mice by decreased expression of NET and MAOA and a lack of TH upregulation induced by food deprivation as in wild-type mice.

Animals↗
PubMed1998

Neuropeptide Y mRNA and serotonin innervation in the arcuate nucleus of anorexia mutant mice.

The anorexia (anx) mutation causes reduced food intake in preweanling mice, resulting in death from starvation within 3-4 weeks. In wild-type rodents, starvation induces increased neuropeptide Y (NPY) mRNA levels in the arcuate nucleus that promotes compensatory hyperphagia. Despite severely decreased body weight and food intake at 3-weeks age, anx/anx mice do not show elevated NPY mRNA levels in the hypothalamic arcuate nucleus compared to wild-type/heterozygous littermates. The NPY mRNA levels can be upregulated in normal mice at this chronological age, because 24-h food deprivation increased arcuate NPY mRNA in wild-type littermates. The unresponsiveness of NPY expression in the arcuate of anx/anx mice was paralleled by serotonergic hyperinnervation of the arcuate nucleus, comparable to the serotonergic hyperinnervation previously reported in the rest of the anx/anx brain. This result is consistent with the hypothesis that wasting disorders are accompanied by disregulation of NPY mRNA expression in the arcuate nucleus, and suggests that reduced food intake, the primary behavioral phenotype of the anx/anx mouse, may be the result of altered hypothalamic mechanisms that normally regulate feeding.

Animals↗
PubMed1997

Monitoring catecholamine differentiation in the embryonic brain and peripheral neurons using E. coli lacZ as a reporter gene.

An X-gal based histochemical assay was used to detect catecholamine (CA) cells in transgenic mouse embryos, in which the expression of the lacZ reporter was driven by the tissue-specific promoter of the rat tyrosine hydroxylase (TH) gene. As the first enzyme in the biosynthetic pathway for CA neurotransmitters, TH is a specific phenotypic marker for CA cells in the central and peripheral nervous systems of adult animals. During embryogenesis, TH expression appears permanently within CA-producing cells, and transiently within several other cell types. In this study we were able to monitor TH expression in transgenic mouse embryos by following the expression of the lacZ reporter in substantia nigral dopaminergic neurons in the central nervous system, the trigeminal (V) sensory ganglia, and dorsal root ganglia in the periphery. Our results demonstrate that the rat TH promoter-lacZ transgene provides an important experimental tool for monitoring catecholaminergic lineage cells during embryogenesis.

Animals↗
PubMed1997

Induction of interferon-gamma inducing factor in the adrenal cortex.

Interferon-gamma inducing factor (IGIF) is a recently identified cytokine also called interleukin-1gamma (IL-1gamma) or interleukin-18 (IL-18). Its biological activity is pleiotropic, and, so far, it has been shown to induce interferon-gamma production in Th1 cells, to augment the production of granulocyte-macrophage-CSF, and to decrease that of interleukin-10 (IL-10). We first detected newly synthesized IGIF mRNA by differential display in the adrenal gland of reserpine-treated rats and then isolated two transcripts by reverse transcription polymerase chain reaction. They were identified as rat IGIF on the basis of the high homology with mouse: 91% at both the nucleotide and the amino acid level. Subsequently, we investigated the effects of stress on IGIF mRNA levels and found that acute cold stress strongly induced IGIF gene expression. In situ hybridization analysis showed that IGIF is synthesized in the adrenal cortex, specifically in the zona reticularis and fasciculata that produce glucocorticoids. The presence of IGIF mRNA was also detected in the neurohypophysis although induction by stress was not significant. Our results call for more attention to the role of the adrenal gland as a potential effector of immunomodulation and suggest that IGIF itself might be a secreted neuroimmunomodulator and play an important role in orchestrating the immune system following a stressful experience.

Adrenal Cortex↗