The prevalence of obesity is rapidly growing throughout the developing and developed world. Given the seriousness of obesity, it critically needs to develop new therapeutic ways to defend against its growth. Persistent increase in food intake is a primary cause of the energy imbalance. The arcuate nucleus of the hypothalamus is a key region to integrate signals originating from various regions in periphery and leptin resistance in the central nervous system (CNS) contributes to the impaired regulation of food intake. It has been endeavor to treat obesity by understanding the mechanisms of CNS regulation of food intake. Adipose tissue has been regarded as a tumor because of its reversible expansibility and dependency on vasculature. There has been a challenge to starve adipose tissue by inhibiting adipose tissue vasculature. A peptide to cause apoptosis of endothelium only in white adipose tissue greatly loses body weight by reducing food intake independent of the action of leptin. This study provides convincing evidence for a previously unknown relationship between the status of adipose tissue vasculature and the regulation of food intake that may provide a novel way for decreasing body fat. However, the mechanism by which the inhibition of angiogenesis in white adipose tissue decreases food intake and body weight remains unclear. In this review, we describe the potential mechanisms of regulation of food intake induced by inhibition of angiogenesis in white adipose tissue.
Adipose Tissue ; Adipose Tissue, White ; Apoptosis ; Arcuate Nucleus ; Body Weight ; Central Nervous System ; Dependency (Psychology) ; Eating ; Endothelium ; Hypothalamus ; Leptin ; Obesity ; Prevalence

OBJECTIVE: The ubiquitous human polyomavirus, JC virus(JCV) is the etiologic agent of the fatal demyelinating central nervous system(CNS) disease, progressive multifocal leukoencephalopathy(PML). Recent studies have reported the detection of the JCV in samples derived from several type of human neural tumors and suggested the possible association of JCV with CNS tumors. Here we report for the first time, the presence of JCV in Korean glioblastoma multiforme(GM) patients. METHODS: Two Korean GM patients were assayed for JCV. To detect JCV, we performed immunohistochemical analysis using anti-JCV and anti-glial fibrillary acidic protein(GFAP) serum and polymerase chain reaction(PCR) using primers. RESULTS: JCV antigen was detected in cytoplasm abundantly in cells of this tumor case. Also, GFAP immunoreactivity was predominantly observed in cytoplasm of the cells that were morphologically bizarred appearing astrocytes in GM. In addition, both of the large T antigen gene and the VP1 gene were detected and this result correspond with previous result of immunohistochemistry. CONCLUSION: Although it is not certain that GM is associated with the JCV, we are attempted to elucidate the possible implication of JCV in the tumorigenesis of certain human malignant gliomas.
Antigens, Viral, Tumor ; Astrocytes ; Brain* ; Carcinogenesis ; Cytoplasm ; Glioblastoma* ; Glioma ; Humans ; Immunohistochemistry ; JC Virus*

The effects of crude saponin (SAP) and alkaloid (ALK) fractions of Panax ginseng C.A. Meyer on the detrimental effects of electroconvulsive shock (ECS) and scopolamine on passive avoidance response (PAR) were studied in male Sprague-Dawley rats, referring their effects on the neuronal injury and plasticity of hippocampus in response to electrolytic lesion of left entorhinal cortex (ECL). The detrimental ECS effect on PAR was attenuated by pre- and post-treatments with SAP and ALK, respectively, or by pretreatment with aminoguanidine (AG), an inhibitor of diamine oxidase and NO synthase. And the detrimental scopolamine effect on PAR was also inhibited by pretreatment with ALK or AG, and by posttreatment with SAP or ALK, respectively. On the 7th day after ECL, the brain sections stained by cresyl violet and by acetylcholinesterase (AChE) histochemistry, respectively, showed the chromatolysis and numeral decrease of neurons and the reduction of AChE reactivity in the hippocampus CA1 area and to a lesser extent, in the dentate gyrus. The neuronal cell death of the CA1 area was significantly reduced by SAP, ALK, or AG, and the reduction of AChE reactivity was significantly attenuated by SAP or ALK and to a lesser extent by AG. These results suggests that the protective effect of ginseng SAP and ALK fractions on ECS- or scopolamine-induced impairment of PAR may be ascribed in part to preservation of hippocampal neurons, particularly cholinergic neurons.
Acetylcholinesterase ; Amine Oxidase (Copper-Containing) ; Brain ; Cell Death ; Cholinergic Neurons ; Cholinesterases ; Dentate Gyrus ; Electroshock ; Entorhinal Cortex ; Hippocampus* ; Humans ; Male ; Neurons* ; Nitric Oxide Synthase ; Panax* ; Plastics ; Rats, Sprague-Dawley ; Saponins ; Scopolamine Hydrobromide ; Viola

As part of a study on the effects of dexamethasone and dehydroepiandrosterone (DHEA) on the biological roles of astrocytes in brain injury, this study evaluated the effects of dexamethasone and DHEA on the responses of primary cultured rat cortical astrocytes to lipopolysaccharide (LPS) and antimycin A. Dexamethasone decreased spontaneous release of LDH from astrocytes, and the dexamethasone effect was inhibited by DHEA. However, the inhibitory effect of DHEA on the dexamethasone-induced decrease of LDH release was not shown in astrocytes treated with LPS, and antimycin A-induced LDH release was not affected by dexamethasone or DHEA. Unlike dexamethasone, DHEA increased MTT value of astrocytes and also attenuated the antimycin A-induced decrease of MTT value. Glutamine synthetase activity of astrocytes was not affected by DHEA or LPS but increased by dexamethasone, and the dexamethasone-dependent increase was attenuated by DHEA. However, antimycin A markedly decreased glutamine synthetase activity, and the antimycin A effect was not affected by dexamethasone or DHEA. Basal release of (3H)arachidonic acid from astrocytes was moderately increased by LPS and markedly by antimycin A. Dexamethasone inhibited the basal and LPS-dependent releases of (3H)arachidonic acid, but neither dexamethasone nor DHEA affected antimycin A-induced (3H)arachidonic acid release. Basal IL-6 release from astrocytes was not affected by dexamethasone or DHEA but markedly increased by LPS and antimycin A. LPS-induced IL-6 release was attenuated by dexamethasone but was little affected by DHEA, and antimycin A-induced IL-6 release was attenuated by DHEA as well as dexamethasone. At the concentration of dexamethasone and DHEA which does not affect basal NO release from astrocytes, they moderately inhibited LPS-induced NO release but little affected antimycin A-induced decrease of NO release. Taken together, these results suggest that dexamethasone and DHEA, in somewhat different manners, modulate the astrocyte reactivity in brain injuries inhibitorily.
Animals ; Antimycin A* ; Arachidonic Acid ; Astrocytes* ; Brain Injuries ; Dehydroepiandrosterone* ; Dexamethasone* ; Glutamate-Ammonia Ligase ; Interleukin-6 ; Nitric Oxide ; Rats*

Hepatic stellate cells (HSCs) are known to play a role in the pathogenesis of the increased intrahepatic vascular resistance found in chronic liver diseases. The aim of this study was to evaluate the K+ and Ca2+ currents in cultured HSCs from rat liver, through the patch-clamp technique. Most cells were positive for desmin immunostain after isolation and in alpha-smooth muscle actin immunostain after 10 - 14 days of culturing. Outward and inward rectifying K+ currents were confirmed. Two different types of K+ currents were distinguished: one with the inward rectifying current and the other without. The outward K+ currents consisted of at least four components: tetraethylammonium (TEA) -sensitive current, 4-aminopyridine (4-AP) -sensitive current, pimozide-sensitive current and three blocker-resistant current. The peaks of the outward K+ currents evoked by a depolarizing pulse were decreased to 32.0 +/- 3.0, 62.8 +/- 3.7 and 32.8 +/- 3.5% by 5 mM TEA, 2 mM 4-AP and 15microM pimozide, respectively. Moreover, the combined application of three blockers caused 86.6 +/- 4.8% suppression. The inward currents evoked hyperpolarizing pulses were inwardly rectifying and almost blocked by Ba2+. Elevation of external K+ increased the inward current amplitude and positively shifted its reversal potential. Voltage- dependent Ca2+ currents which were completely abolished by Cd2+ and nimodipine were detected in 14 day cultured HSCs. In this study, the cultured HSCs were found to express outward K+ currents composed of multiple pharmacological components, Ba2+-sensitive inward rectifying K+ current and L-type Ca2+ current.
Animals ; Calcium/*metabolism ; Calcium Channel Blockers/pharmacology ; Calcium Channels, L-Type/*physiology ; Cells, Cultured ; Hepatocytes/cytology/*physiology ; Immunohistochemistry ; Male ; Membrane Potentials/drug effects/physiology ; Patch-Clamp Techniques ; Potassium/*metabolism ; Potassium Channel Blockers/pharmacology ; Potassium Channels, Voltage-Gated/*physiology ; Rats ; Rats, Sprague-Dawley

We studied the sex different nicotine effect on evoked population spike amplitudes (ePSA) and connexin (Cx) expression in the hippocampus CA1 area of gerbils. Acute doses of nicotine bitartrate (0.5 mg/kg: NT-0.5) slightly reduced ePSA in males but markedly augmented that in females. Acute NT (5.0 mg/kg) markedly increased the ePSA in all gerbils. Unlike acute NT-0.5, repeated NT-0.5 injection (twice a day for 7 days) significantly increased the ePSA in males and slightly affected the NT-0.5 effect in females. The Cx36 and Cx43 expression levels as well as Cx expressing neuronal populations were significantly increased by repeated NT-0.5 in in both male and female gerbils, and particularly, Cx43 expression was somewhat prominent in females. These results demonstrated a sex difference with respect to the nicotine effect on hippocampal bisynaptic excitability, irrelevant to connexin expression.
Animals ; Connexins ; Connexin 43 ; Female ; Gerbillinae* ; Hippocampus ; Male ; Neurons* ; Nicotine* ; Sex Characteristics*

New-born cells continue to proliferate and survive to become mature granule cells in adult rat hippocampus. Although this process, known as neurogenesis, is inhibited by acute stress, it is not clear whether chronic stress affects neurogenesis. To determine whether chronic mild stress (CMS) influences neurogenesis in the adult rat hippocampus, male Sprague-Dawley rats were exposed to CMS and administered bromodeoxyuridine (BrdU) before or after CMS to observe the survival/differentiation or proliferation of new-born cells, respectively. In addition, we measured brain-derived neurotrophic factor (BDNF) mRNA in the granule cell layer (GCL) of the hippocampus, because BDNF is known to play an important role in the survival of new-born cells. CMS significantly decreased the survival of newborn cells in the GCL, but did not influence the proliferation or differentiation of new-born cells. CMS did not affect the proliferation and survival of new-born cells in the hilus. In addition, CMS did not change BDNF mRNA levels in the GCL. These results demonstrate that CMS reduces the survival of new-born cells but not of their proliferation, suggesting that repeated mild stress could influence a part of neurogenesis, but not the whole part of neurogenesis. These results raise the possibility that the survival of new-born cells may be suppressed in the presence of normal BDNF mRNA levels in GCL.
Animals ; Brain-Derived Neurotrophic Factor/metabolism ; Bromodeoxyuridine/*administration & dosage ; Calcium-Binding Protein, Vitamin D-Dependent/metabolism ; Cell Proliferation ; Cell Survival ; Comparative Study ; Fluorescein-5-isothiocyanate ; Fluorescent Antibody Technique, Indirect ; Fluorescent Dyes ; Glial Fibrillary Acidic Protein/metabolism ; Hippocampus/cytology/growth & development/*pathology ; Immunohistochemistry ; In Situ Hybridization ; Male ; Microscopy, Confocal ; RNA, Messenger/metabolism ; Rats ; Rats, Sprague-Dawley ; Research Support, Non-U.S. Gov't ; Restraint, Physical ; Rhodamines ; Stress/pathology/*physiopathology

Recent studies suggest that alterations in glutamate receptor subunit levels in mesocorticolimbic dopamine areas could account for neural adaptations in response to psychostimulant drugs. Although many drugs of abuse induce changes in ionotropic glutamate receptor subunits in mesocorticolimbic dopamine areas, the changes of ionotropic glutamate receptor subunits by repeated nicotine treatment in these areas are not known. To answer this question, we injected male Sprague-Dawley rats twice daily with nicotine (0.4 mg/kg) or saline (1 ml/kg) for 10 days. The immunoreactivity of NR1, GluR1, and GluR2 glutamate receptor subunits was examined 16~18 h after the last injection of saline or nicotine. Repeated nicotine treatment significantly increased NR1 levels in the ventral tegmental area (VTA). In addition, repeated nicotine treatment showed a tendency towards an increase in GluR1 levels in the VTA as well as in striatum. However, there was no significant change in glutamate receptor subunits in other areas including nucleus accumbens (NAc). These results demonstrate that repeated nicotine treatment increases NR1 levels in VTA similarly to other drugs of abuse, suggesting that elevated glutamate receptor subunits in the VTA, but not NAc may be involved in the excitation of mesocorticolimbic dopamine neurons by nicotine.
Dopamine* ; Glutamic Acid* ; Humans ; Male ; Neurons ; Nicotine* ; Nucleus Accumbens ; Rats, Sprague-Dawley ; Receptors, Glutamate* ; Street Drugs ; Ventral Tegmental Area