Changes of myelin basic protein in the hippocampus of an animal model of type 2 diabetes / 한국실험동물학회지

In this study, we observed chronological changes in the immunoreactivity and expression level of myelin basic protein (MBP), one of the most abundant proteins in the central nervous system, in the hippocampus of Zucker diabetic fatty (ZDF) rats and their control littermates (Zucker lean control; ZLC). In the ZLC group, body weight steadily increased with age; the body weight of the ZDF group, however, peaked at 30 weeks of age, and subsequently decreased. Based on the changes of body weight, animals were divided into the following six groups: early (12-week), middle (30-week), and chronic (52-week) diabetic groups and their controls. MBP immunoreactivity was found in the alveus, strata pyramidale, and lacunosum-moleculare of the CA1 region, strata pyramidale and radiatum of the CA3 region, and subgranular zone, polymorphic layer, and molecular layer of the dentate gyrus. MBP immunoreactivity was lowest in the hippocampus of 12-week-old rats in the ZLC group, and highest in 12-week-old rats in the ZDF group. Diabetes increased MBP levels in the 12-week-old group, while MBP immunoreactivity decreased in the 30-week-old group. In the 52-week-old ZLC and ZDF groups, MBP immunoreactivity was detected in the hippocampus, similar to the 30-week-old ZDF group. Western blot results corroborated with immunohistochemical results. These results suggested that changes in the immunoreactivity and expression of MBP in the hippocampus might be a compensatory response to aging, while the sustained levels of MBP in diabetic animals could be attributed to a loss of compensatory responses in oligodendrocytes.

Reduction of adult hippocampal neurogenesis is amplified by aluminum exposure in a model of type 2 diabetes

In this study, we investigated the effects of chronic aluminum (Al) exposure for 10 weeks on cell proliferation and neuroblast differentiation in the hippocampus of type 2 diabetic rats. Six-week-old Zucker diabetic fatty (ZDF) and Zucker lean control (ZLC) rats were selected and randomly divided into Al- and non-Al-groups. Al was administered via drinking water for 10 weeks, after which the animals were sacrificed at 16 weeks of age. ZDF rats in both Al- and non-Al-groups showed increases in body weight and blood glucose levels compared to ZLC rats. Al exposure did not significantly affect body weight, blood glucose levels or pancreatic β-cells and morphology of the pancreas in either ZLC or ZDF rats. However, exposure to Al reduced cell proliferation and neuroblast differentiation in both ZLC and ZDF rats. Exposure to Al resulted in poor development of the dendritic processes of neuroblasts in both ZLC and ZDF rats. Furthermore, onset and continuation of diabetes reduced cell proliferation and neuroblast differentiation, and Al exposure amplified reduction of these parameters. These results suggest that Al exposure via drinking water aggravates the impairment in hippocampal neurogenesis that is typically observed in type 2 diabetic animals.

Effects of aluminum on the reduction of neural stem cells, proliferating cells, and differentiating neuroblasts in the dentate gyrus of D-galactose-treated mice via increasing oxidative stress

Aluminum (Al) accumulation increases with aging, and long-term exposure to Al is regarded as a risk factor for Alzheimer's disease. In this study, we investigated the effects of Al and/or D-galactose on neural stem cells, proliferating cells, differentiating neuroblasts, and mature neurons in the hippocampal dentate gyrus. AlCl3 (40 mg/kg/day) was intraperitoneally administered to C57BL/6J mice for 4 weeks. In addition, vehicle (physiological saline) or D-galactose (100 mg/kg) was subcutaneously injected to these mice immediately after AlCl3 treatment. Neural stem cells, proliferating cells, differentiating neuroblasts, and mature neurons were detected using the relevant marker for each cell type, including nestin, Ki67, doublecortin, and NeuN, respectively, via immunohistochemistry. Subchronic (4 weeks) exposure to Al in mice reduced neural stem cells, proliferating cells, and differentiating neuroblasts without causing any changes to mature neurons. This Al-induced reduction effect was exacerbated in D-galactose-treated mice compared to vehicle-treated adult mice. Moreover, exposure to Al enhanced lipid peroxidation in the hippocampus and expression of antioxidants such as Cu, Zn- and Mn-superoxide dismutase in D-galactose-treated mice. These results suggest that Al accelerates the reduction of neural stem cells, proliferating cells, and differentiating neuroblasts in D-galactose-treated mice via oxidative stress, without inducing loss in mature neurons.

Comparison of pharmacological and genetic inhibition of cyclooxygenase-2: effects on adult neurogenesis in the hippocampal dentate gyrus

Inducible cyclooxygenase-2 (COX-2) has received much attention because of its role in neuro-inflammation and synaptic plasticity. Even though COX-2 levels are high in healthy animals, the function of this factor in adult neurogenesis has not been clearly demonstrated. Therefore, we performed the present study to compare the effects of pharmacological and genetic inhibition of COX-2 on adult hippocampal neurogenesis. Physiological saline or the same volume containing celecoxib was administered perorally every day for 5 weeks using a feeding needle. Compared to the control, pharmacological and genetic inhibition of COX-2 reduced the appearance of nestin-immunoreactive neural stem cells, Ki67-positive nuclei, and doublecortin-immunoreactive neuroblasts in the dentate gyrus. In addition, a decrease in phosphorylated cAMP response element binding protein (pCREB) at Ser133 was observed. Compared to pharmacological inhibition, genetic inhibition of COX-2 resulted in significant reduction of neural stem cells, cell proliferation, and neuroblast differentiation as well as pCREB levels. These results suggest that COX-2 is part of the molecular machinery that regulates neural stem cells, cell proliferation, and neuroblast differentiation during adult hippocampal neurogenesis via pCREB. Additionally, genetic inhibition of COX-2 strongly reduced neural stem cell populations, cell proliferation, and neuroblast differentiation in the dentate gyrus compared to pharmacological inhibition.

Treadmill exercise prevents diabetes-induced increases in lipid peroxidation and decreases in Cu,Zn-superoxide dismutase levels in the hippocampus of Zucker diabetic fatty rats

In the present study, we investigated the effects of treadmill exercise on lipid peroxidation and Cu,Zn-superoxide dismutase (SOD1) levels in the hippocampus of Zucker diabetic fatty (ZDF) rats and lean control rats (ZLC) during the onset of diabetes. At 7 weeks of age, ZLC and ZDF rats were either placed on a stationary treadmill or made to run for 1 h/day for 5 consecutive days at 16~22 m/min for 5 weeks. At 12 weeks of age, the ZDF rats had significantly higher blood glucose levels and body weight than the ZLC rats. In addition, malondialdehyde (MDA) levels in the hippocampus of the ZDF rats were significantly higher than those of the ZLC rats whereas SOD1 levels in the hippocampus of the ZDF rats were moderately decreased. Notably, treadmill exercise prevented the increase of blood glucose levels in ZDF rats. In addition, treadmill exercise significantly ameliorated changes in MDA and SOD1 levels in the hippocampus although SOD activity was not altered. These findings suggest that diabetes increases lipid peroxidation and decreases SOD1 levels, and treadmill exercise can mitigate diabetes-induced oxidative damage in the hippocampus.

Cell proliferation and neuroblast differentiation in the dentate gyrus of high-fat diet-fed mice are increased after rosiglitazone treatment

In this study, we determined how rosiglitazone (RSG) differentially affected hippocampal neurogenesis in mice fed a low-fat diet (LFD) or high-fat diet (HFD; 60% fat). LFD and HFD were given to the mice for 8 weeks. Four weeks after initiating the LFD and HFD feeding, vehicle or RSG was administered orally once a day to both groups of mice. We measured cell proliferation and neuroblast differentiation in the subgranular zone of the dentate gyrus using Ki67 and doublecortin (DCX), respectively, as markers. In addition, we monitored the effects of RSG on the levels of DCX and brain-derived neurotrophic factor (BDNF) in hippocampal homogenates. At 8 weeks after the LFD feeding, the numbers of Ki67- and DCX-positive cells as well as hippocampal levels of DCX and BDNF were significantly decreased in the RSG-treated group compared to the vehicle-treated animals. In contrast, the numbers of Ki67- and DCX-positive cells along with hippocampal levels of DCX and BDNF in the HFD fed mice were significantly increased in the RSG-treated mice compared to the vehicle-treated group. Our data demonstrate that RSG can modulate the levels of BDNF, which could play a pivotal role in cell proliferation and neuroblast differentiation in the hippocampal dentate gyrus.

Intragastric gavage with denatonium benzoate acutely induces neuronal activation in the solitary tract nucleus via the vagal afferent pathway

Natural toxic substances have a bitter taste and their ingestion sends signals to the brain leading to aversive oral sensations. In the present study, we investigated chronological changes in c-Fos immunoreactivity in the nucleus tractus solitarius (NTS) to study the bitter taste reaction time of neurons in the NTS. Equal volumes (0.5 mL) of denatonium benzoate (DB), a bitter tastant, or its vehicle (distilled water) were administered to rats intragastrically. The rats were sacrificed at 0, 0.5, 1, 2, 4, 8, or 16 h after treatment. In the vehicle-treated group, the number of c-Fos-positive nuclei started to increase 0.5 h after treatment and peaked 2 h after gavage. In contrast, the number of c-Fos-positive nuclei in the DB-treated group significantly increased 1 h after gavage. Thereafter, the number of c-Fos immunoreactive nuclei decreased over time. The number of c-Fos immunoreactive nuclei in the NTS was also increased in a dose-dependent manner 1 h after gavage. Subdiaphragmatic vagotomy significantly decreased DB-induced neuronal activation in the NTS. These results suggest that intragastric DB increases neuronal c-Fos expression in the NTS 1 h after gavage and this effect is mediated by vagal afferent fibers.

A Case of Abdominal Actinomycosis Presenting as Ileocecal Ulcers and Recurrent Lower Gastrointestinal Bleeding

Abdominal actinomycosis is a rare chronic suppurative infection that is difficult to diagnose precisely without an operation. It also tends to be misdiagnosed as a malignancy, intestinal tuberculosis, diverticular disease, or Crohn's disease. A 54-year-old man presented with loose stools, hematochezia, and vague abdominal pain in the right lower quadrant. He had had a history of hematochezia and recurrent colon ulcers on colonoscopy seven times within the past 3 years. A colonoscopy at admission revealed multiple, variably sized and shaped ulcerations in the terminal ileum, cecum, and ascending and transverse colons. Biopsies from the cecal ulcer demonstrated sulfur granules. This is the first cases of abdominal actinomycosis presenting as a recurrent lower gastrointestinal hemorrhage due to ileocolic ulcerations in Korea.

Differential effects of treadmill exercise on cyclooxygenase-2 in the rat hippocampus at early and chronic stages of diabetes / 한국실험동물학회지

Cyclooxygenase-2 (COX-2) is believed to be a multifunctional neural modulator that affects synaptic plasticity in the hippocampus. In the present study, we investigated the differential effects of treadmill exercise on COX-2 immunoreactivity in the dentate gyrus in early and chronic diabetic stages in Zucker diabetic fatty (ZDF) rats and lean control (ZLC) rats. To this end, ZLC and ZDF rats at 6 or 23 weeks of age were put on a treadmill with or without running for 1 h/day for 5 consecutive days at 16-22 m/min for 5 weeks or 12-16 m/min for 7 weeks, respectively. Treadmill exercise in prediabetic and chronic diabetic rats significantly reduced blood glucose levels. In particular, exercise in the prediabetic rat blocked the onset of diabetes. COX-2 immunoreactivity was mainly detected in the granule cell layer of the dentate gyrus and stratum pyramidale of the CA3 region in all groups. COX-2 immunoreactivity was significantly increased in these regions of ZLC and ZDF rats after treadmill exercise in the early diabetic stage. However, COX-2 immunoreactivity was not changed in these regions in ZDF rats after treadmill exercise in the chronic stage. These results suggest that treadmill exercise in diabetic animals in the chronic stage has limited ability to cause plasticity in the dentate gyrus.

Selective Proximal Tubule Injury and Progressive Renal Failure due to Ifosfamide and Cisplatin in a Patient with Ovarian Cancer / 대한신장학회지

Ifosfamide-induced nephrotoxicity is usually manifested in the form of Fanconi syndrome and the combination of cisplatin enhances ifosfamide-induced nephrotoxicity. We here report a case of report specific proximal tubular dysfunction and progressive renal failure after ifosfamide and cisplatin chemotherapy in a 32-year old woman with ovarian cancer. The patient was referred to our department due to severe hypokalemia and elevated serum creatinine. Her renal function was abruptly impaired and serum and urine electrolytes were consistent with Fanconi syndrome. The kidney biopsy revealed atrophy and falling of renal tubular cells, and immunohistochemical staining with aquaporin 1 (AQP1) revealed that injured epithelial cells were proximal tubular cells. This finding suggests that ifosfamide selectively impairs proximal tubule function and combination with cisplatin causes progressive renal failure

A Case of High Dose Cytosine Arabinoside Induced Stevens-Johnson Syndrome in a Patient with Malignant Lymphoma

Many chemotherapeutic agents induce variable cutaneous adverse reactions. Among the side effects, Stevens-Johnson syndrome is rare, but a fatal complication. There are two prior reports of cytosine arabinoside (ARA-C) induced toxic epidermal necrolysis, which is considered in the continuum of Stevens- Johnson syndrome. The prior cases were female patients under 16 years old with acute lymphocytic leukemia. We treated a 77-year-old man with recurrent mantle cell lymphoma who developed Stevens- Johnson syndrome after high dose ARA-C therapy. This is the first case of ARA-C induced Stevens- Johnson syndrome in Korea.

Intraductal Papillary Mucinous Neoplasm in a Patient with an Incomplete Pancreatic Divisum / 대한소화기내시경학회지

Intraductal papillary mucinous neoplasms (IPMNs) are premalignant lesions that require a surgical resection. IPMN can cause abdominal pain or pancreatitis as a result of either mucin production or a papillary growth, resulting in a ductal obstruction. Most IPMNs arise from the main pancreatic duct. However, IPMNs arising from the accessory pancreatic duct are extremely rare. Pancreatic divisum occurs when the ventral and dorsal ducts of the pancreas fail to fuse during organogenesis. It is the most common congenital variant of pancreatic-ductal development, and occurs in approximately 10~14% of individuals. Although pancreatic divisum has no clinical relevance, some patients present with acute recurrent or chronic pancreatitis. In most cases, it is discovered incidentally during an examination of pancreatitis, and is occasionally accompanied by a pancreatic tumor. We report the first case of IPMN in a patient with an incomplete pancreatic divisum in Korea.