J Vet Sci.  2014 Mar;15(1):27-33. 10.4142/jvs.2014.15.1.27.

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

• Yoo DY
• Kim W
• Kim DW
• Nam SM
• Jung HY
• Kim JW
• Lee CH
• Choi JH
• Won MH
• Yoon YS
• Hwang IK

• KMID: 1737607
• DOI: http://doi.org/10.4142/jvs.2014.15.1.27

Abstract

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.

Keyword

brain-derived neurotrophic factor; dentate gyrus; high-fat diet; rosiglitazone

MeSH Terms

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
Brain-Derived Neurotrophic Factor
Hypoglycemic Agents
Ki-67 Antigen
Microtubule-Associated Proteins
Neuropeptides
Thiazolidinediones

Figure

• 

  Fig. 1 Immunohistochemistry specific for Ki67 in the dentate gyrus. Ki67-positive nuclei were detected in the subgranular zone of the dentate gyrus. The number of Ki67-immunoreactive nuclei was decreased in the LFD-RSG group compared to the LFD-Vehicle group. Ki67-positive nuclei were rarely seen in the HFD-Vehicle group unlike the LFD-Vehicle group. The number of Ki67-positive nuclei was significantly increased in the HFD-RSG group compared to the HFD-Vehicle group. (A) low-fat diet (LFD)-fed vehicle-treated group (LFD-Vehicle). (B) LFD-fed rosiglitazone (RSG)-treated group (LFD-RSG). (C) high-fat diet (HFD)-fed vehicle-treated group (HFD-Vehicle). (D) HFD-fed RSG-treated (HFD-RSG) groups. (E) Relative numbers of Ki67-immunoreactive nuclei in the LFD-Vehicle, LFD-RSG, HFD-Vehicle, and HFD-RSG groups (n = 7 per group; *p < 0.05, Vehicle versus RSG groups; †p < 0.05, LFD versus HFD groups). All data are expressed as the mean ± standard error of the mean (SEM). ML: molecular layer, GCL: granule cell layer, PoL: polymorphic layer. Scale bar = 50 µm.

• 

  Fig. 2 Immunohistochemistry specific for DCX in the dentate gyrus. DCX-positive neuroblasts were detected in the subgranular zone of the dentate gyrus. The number of DCX-immunoreactive neuroblasts was decreased in the LFD-RSG group compared to the LFD-Vehicle group. DCX-positive neuroblasts were rarely seen in the HFD-Vehicle group unlike the LFD-Vehicle group. The number of DCX-immunoreactive neuroblasts in the dentate gyrus was increased in the HFD-RSG group compared to the HFD-Vehicle group. (A and B) LFD-Vehicle. (C and D) LFD-RSG. (E and F) HFD-Vehicle. (G and H) HFD-RSG groups. (I) Relative number of DCX-immunoreactive cells in the LFD-Vehicle, LFD-RSG, HFD-Vehicle, and HFD-RSG groups (n = 7 per group; *p < 0.05, Vehicle vs. RSG groups; †p < 0.05, LFD vs. HFD groups). All data are expressed as the mean ± SEM. (J) Western blot analysis of DCX levels in the dentate gyrus of the LFD-Vehicle, LFD-RSG, HFD-Vehicle, and HFD-RSG groups. Relative optical density (ROD) of the bands is expressed as percentages (n = 5 per group; *p < 0.05, Vehicle vs. RSG groups; †p < 0.05, LFD vs. HFD groups). Data are presented as the mean ± SEM. Scale bars = 25 µm (B, D, F, and H) or 50 µm (A, C, E, and G).

• 

  Fig. 3 BDNF levels in the hippocampal homogenates from the LFD-Vehicle, LFD-RSG, HFD-Vehicle, and HFD-RSG groups (n = 5 per group; *p < 0.05, LFD vs. HFD groups; †p < 0.05, Vehicle vs. RSG groups). All data are expressed as the mean ± SEM.

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