No abstract available.
Aneurysm*

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.
Aluminum/*toxicity ; Animals ; Blood Glucose/analysis ; Cell Differentiation/drug effects ; Cell Proliferation/drug effects ; Diabetes Mellitus, Experimental/pathology ; Diabetes Mellitus, Type 2/*pathology ; Disease Models, Animal ; Hippocampus/*drug effects ; Neurogenesis/*drug effects ; Random Allocation ; Rats, Zucker

PURPOSE: The purpose of this study was to investigate the microstructural changes according to aging on the thickness and signal intensity (SI) of the cortical gray matter (GM) and white matter (WM) on the T2-, fluid-attenuated inversion recovery (FLAIR) and T1-weighted MR images in normal subjects. MATERIALS AND METHODS: The 10, 20, 30, 40, 50, 60, 70, 80 and 90 year age groups of men and women (each 10 individuals) who underwent routine brain MRI, including the T2-, FLAIR and T1-weighted images, were selected for this study. We measured the thickness and the SI of the cortical GM and WM at the postcentral gyrus, which has an even thickness at the level of centrum semiovale, on the axial scans and we calculated the mean values of the thickness ratio of the gray/white matter (TRGW) and the signal intensity ratio of the gray/white matter (SRGW), and we compared the ratios of each age group. RESULTS: On the T2-weighted images, the TRGWs were 0.81 and 0.79 at the age of 10 and they were 0.73 and 0.71 at the age of 90 in the men and women, respectively. So, the GM thickness was decreased more than the WM thickness was with aging. On the FLAIR images, the TRGWs were 1.09 and 1.00 at the age of 10 and they were 1.11 and 0.95 at the age of 70 in the men and women, respectively. On the T1-weighted images, the TRGWs were 0.66 and 0.80 at the age of 10, and the ratio was changed to 0.90 and 0.78 at the age of 90 in the men and women, respectively. On the T2-weighted image, the SRGWs were 1.53 and 1.43 at the age of 10, and they were 1.23 and 1.27 at the age of 90 in the men and women, respectively. On the FLAIR images, the SRGWs were 1.23 and 1.25 at the age of 10 and they were 1.06 and 1.05 at the age of 90 in the men and women, respectively. On the T1-weighted images, the SRGWs were 0.86 and 0.85 at the age of 10, and they were 0.90 and 0.87 at the age of 90 in the men and women, respectively. CONCLUSION: We suggest that the age-related microstructural changes of the thickness and the SI of the cortical GM and WM on the T2-, FLAIR and T1-weighted images are unique, and so this knowledge will be helpful to differentiate neurodegenerative disease from normal aging of the brain.
Aging ; Brain ; Female ; Humans ; Male ; Neurodegenerative Diseases

PURPOSE: The purpose of this study was to investigate the microstructural changes according to aging on the thickness and signal intensity (SI) of the cortical gray matter (GM) and white matter (WM) on the T2-, fluid-attenuated inversion recovery (FLAIR) and T1-weighted MR images in normal subjects. MATERIALS AND METHODS: The 10, 20, 30, 40, 50, 60, 70, 80 and 90 year age groups of men and women (each 10 individuals) who underwent routine brain MRI, including the T2-, FLAIR and T1-weighted images, were selected for this study. We measured the thickness and the SI of the cortical GM and WM at the postcentral gyrus, which has an even thickness at the level of centrum semiovale, on the axial scans and we calculated the mean values of the thickness ratio of the gray/white matter (TRGW) and the signal intensity ratio of the gray/white matter (SRGW), and we compared the ratios of each age group. RESULTS: On the T2-weighted images, the TRGWs were 0.81 and 0.79 at the age of 10 and they were 0.73 and 0.71 at the age of 90 in the men and women, respectively. So, the GM thickness was decreased more than the WM thickness was with aging. On the FLAIR images, the TRGWs were 1.09 and 1.00 at the age of 10 and they were 1.11 and 0.95 at the age of 70 in the men and women, respectively. On the T1-weighted images, the TRGWs were 0.66 and 0.80 at the age of 10, and the ratio was changed to 0.90 and 0.78 at the age of 90 in the men and women, respectively. On the T2-weighted image, the SRGWs were 1.53 and 1.43 at the age of 10, and they were 1.23 and 1.27 at the age of 90 in the men and women, respectively. On the FLAIR images, the SRGWs were 1.23 and 1.25 at the age of 10 and they were 1.06 and 1.05 at the age of 90 in the men and women, respectively. On the T1-weighted images, the SRGWs were 0.86 and 0.85 at the age of 10, and they were 0.90 and 0.87 at the age of 90 in the men and women, respectively. CONCLUSION: We suggest that the age-related microstructural changes of the thickness and the SI of the cortical GM and WM on the T2-, FLAIR and T1-weighted images are unique, and so this knowledge will be helpful to differentiate neurodegenerative disease from normal aging of the brain.
Aging ; Brain ; Female ; Humans ; Male ; Neurodegenerative Diseases

PURPOSE: Hypertension may be involved an alteration of intrinsic basal tone in vascular smooth muscle. The purpose of this study was to investigate the vasorelaxant effect of atrial natriuretic peptide (ANP) on isolated non-contracted aorta from two-kidney, one clip (2K1C) renovascular hypertensive rats. METHODS: 2K1C hypertension was induced by clipping the left renal artery and were used 6 weeks later. Age-matched rats receiving a sham treatment, which served as controls. The thoracic aortae were mounted in tissue baths to measure the isometric tension. RESULTS: ANP diminished basal tone in previously unstimulated thoracic aortic rings from 2K1C hypertensive rats, while it had no effect in the control rats. Endothelial destruction potentiated the vasorelaxant effect of ANP on basal tone in 2K1C rats. A similar potentiation of the ANP response was observed by pre-treatment with N omega-nitro-L-arginine methyl ester (L-NAME) or methylene blue in aortic rings with endothelium. Treatment with calcium-free Krebs decreased basal tone and abolished ANPresponse. These effects were observed only in aortic rings from 2K1C rats. Similarly, staurosporine and calphostin C, inhibitors of protein kinase C (PKC), lowered basal tone and abolished ANP-response in hypertensive rats. CONCLUSION: These results demonstrate that ANP has a vasorelaxant effect on basal tone in 2K1C renovascular hypertension. Inhibition of ANP effects on basal tone by calcium-free Krebs and PKC antagonists suggests that altered Ca2+ -active tone is involved in hypertension, that modifies the response of vascular smooth muscle to the ANP.
Animals ; Aorta ; Aorta, Thoracic ; Atrial Natriuretic Factor ; Baths ; Endothelium ; Hypertension ; Hypertension, Renovascular ; Methylene Blue ; Muscle, Smooth, Vascular ; Naphthalenes ; NG-Nitroarginine Methyl Ester ; Placebos ; Protein Kinase C ; Rats ; Renal Artery ; Salicylamides ; Staurosporine

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.
Adult ; Aging ; Aluminum* ; Alzheimer Disease ; Animals ; Antioxidants ; Dentate Gyrus* ; Galactose ; Hippocampus ; Humans ; Immunohistochemistry ; Lipid Peroxidation ; Mice* ; Nestin ; Neural Stem Cells* ; Neurons ; Oxidative Stress* ; Risk Factors ; Superoxide Dismutase

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.
Animals ; Diabetes Mellitus/enzymology/*metabolism ; Female ; Gene Expression Regulation, Enzymologic ; Genotype ; Hippocampus/*enzymology/metabolism ; Lipid Peroxidation/*physiology ; Male ; Malondialdehyde/metabolism ; Physical Conditioning, Animal/*physiology ; Rats ; Rats, Zucker ; Superoxide Dismutase/genetics/*metabolism

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.
Animals ; Blotting, Western ; Brain-Derived Neurotrophic Factor/metabolism ; Cell Differentiation/*drug effects ; Cell Proliferation/drug effects ; Dentate Gyrus/growth & development/physiology ; Diet, Fat-Restricted ; *Diet, High-Fat ; Hippocampus/growth & development/physiology ; Hypoglycemic Agents/*pharmacology ; Immunohistochemistry ; Ki-67 Antigen/metabolism ; Male ; Mice, Inbred C57BL ; Microtubule-Associated Proteins/metabolism ; Neurogenesis/*drug effects ; Neuropeptides/metabolism ; Thiazolidinediones/*pharmacology

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.
Animals ; Celecoxib/*pharmacology ; Cell Differentiation/drug effects/physiology ; Cell Proliferation/drug effects/physiology ; Cyclooxygenase 2/*genetics/metabolism ; Cyclooxygenase 2 Inhibitors/*pharmacology ; Dentate Gyrus/drug effects/*physiology ; Male ; Mice ; Mice, Knockout ; Neural Stem Cells/drug effects/physiology ; Neurogenesis/drug effects

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.
Adjuvants, Immunologic/pharmacology ; Afferent Pathways/physiology ; Animals ; Injections/veterinary ; Ligands ; Male ; Proto-Oncogene Proteins c-fos/*metabolism ; Quaternary Ammonium Compounds/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, G-Protein-Coupled/*metabolism ; Solitary Nucleus/*physiology ; Vagus Nerve/*drug effects/*physiology