Article

Reduced cell proliferation and neuroblast differentiation in the dentate gyrus of high fat diet-fed mice are ameliorated by metformin and glimepiride treatment.

Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul 151-742, South Korea.
Neurochemical Research (Impact Factor: 2.13). 08/2011; 36(12):2401-8. DOI: 10.1007/s11064-011-0566-3
Source: PubMed

ABSTRACT We investigated the effects of a high-fat diet (HFD) and the subsequent treatment of metformin (met) and glimepiride (glim), which are widely prescribed for type 2 diabetes, on cell proliferation and neuroblast differentiation using Ki67 and doublecortin (DCX) immunohistochemistry, respectively. Animals were fed low-fat diet (LFD) or HFD for 8 weeks. After 5 weeks of the HFD treatment, met alone or met + glim was administered orally once a day for 3 weeks. Body weight and food intake were much higher in the HFD + vehicle-treated group than the LFD-treated group. The administration of met or met + glim to the HFD-treated group resulted in a decrease in weight gain and food intake. Ki67-immunoreactive ((+)) nuclei, DCX(+) neuroblasts and brain-derived neurotrophic factor (BDNF) protein levels were markedly decreased in the dentate gyrus (DG) of the HFD + vehicle-treated group compared to the LFD-treated group. The administration of met or met + glim to the HFD-treated group prevented the reduction of Ki67(+) nuclei, DCX(+) neuroblasts, BDNF levels in the DG. The intraventricular injection of K252a (a BDNF receptor blocker) to the HFD-treated group treated met or met + glim distinctively lowered the reduction of cell proliferation and neuroblast differentiation induced by HFD. These results suggest that a HFD significantly reduces cell proliferation and neuroblast differentiation by reducing BDNF levels and these effects are ameliorated by treatment with met or met + glim.

0 Bookmarks
 · 
123 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Aluminum is the most plentiful metal on the Earth's crust, and its usage in cooking utensils, cosmetics, drinking containers, food additives, pharmaceutical products, and building materials provides many opportunities for potential aluminum consumption. However, its toxicity is low and harmful effects only develop with large-scale deposition of aluminum. In this study, we investigated the effects of subchronic exposure to aluminum (40 mg/kg/day) on neural stem cells, cell proliferation, neuroblast differentiation, and mature neurons in the dentate gyrus of the hippocampus. These experiments were performed in both high-fat diet and low-fat diet-fed C57BL/6J mice via immunohistochemistry using the relevant marker for each cell type, including nestin, Ki67, doublecortin, and NeuN. Subchronic exposure to aluminum in both low-fat and high-fat diet-fed mice reduced neural stem cells, cell proliferation, and neuroblast differentiation without any changes in mature neurons. Furthermore, this reduction effect was exacerbated in high-fat diet-fed mice. These results suggest that aluminum accelerates the reduction of neural stem cells, cell proliferation, and neuroblast differentiation additively or synergistically in high-fat diet-fed mice without any harmful changes in mature neurons.
    Biological trace element research 11/2013; · 1.92 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: This study investigated how rosiglitazone (RSG) differentially affected on the hippocampal neurogenesis in low-fat diet (LFD)- and high-fat diet (HFD)-fed mice. LFD and HFD (60% fat) foods were provided to mice for 8 weeks. Starting from the 4 weeks after 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. In addition, we determined the effects of RSG on the level of DCX and brain-derived neurotrophic factor (BDNF) in hippocampal homogenates. The number of Ki67- and DCX-positive cells and the hippocampal levels of DCX, and BDNF levels were significantly decreased in the RSG-treated group compared to the vehicle-treated group. In contrast, the number of Ki67- and DCX-positive cells and hippocampal levels of DCX, and BDNF were significantly increased in the RSG-treated group compared to the vehicle-treated group. RSG can modulate the levels of BDNF, which could play a pivotal role in cell proliferation and neuroblast differentiation in the hippocampal dentate gyrus; the direction of this modulation depends on the condition of the central nervous system.
    Journal of veterinary science (Suwŏn-si, Korea) 10/2013; · 0.89 Impact Factor