J Vet Sci.  2016 Mar;17(1):13-20. 10.4142/jvs.2016.17.1.13.

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

• Nam SM
• Kim JW
• Yoo DY
• Jung HY
• Choi JH
• Hwang IK
• Seong JK
• Yoon YS

• KMID: 2363330
• DOI: http://doi.org/10.4142/jvs.2016.17.1.13

Abstract

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.

Keyword

Zucker diabetic fatty rat; aluminum; diabetes; drinking water; neurogenesis

MeSH Terms

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
Aluminum
Blood Glucose

Figure

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  Fig. 1 Changes in body weight (A) and blood glucose levels (B) in vehicle-treated Zucker lean control (ZLC), vehicle-treated Zucker diabetic fatty (ZDF), aluminum-treated ZLC (ZLC-Al), and aluminum-treated ZDF (ZDF-Al) rats. Means were analyzed using two-way ANOVA (n = 5 per group; *p < 0.05, indicates a significant difference between ZLC and ZDF or ZLC-AL and ZDF-AL. Error bars indicate the means ± SEM.

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  Fig. 2 Hematoxylin and eosin stain (A, C, E and G) and immunohistochemistry for insulin (B, D, F and H) of the pancreatic islets of the ZLC (A and B), ZLC-Al (C and D), ZDF (E and F), and ZDF-Al (G and H) groups. Note that the islets are slightly enlarged in the ZDF and ZDF-Al groups and insulin immunoreactive β cells are decreased in the ZDF and ZDF-Al groups. However, no histological and immunohistological differences were found between non-Al and Al groups. Scale bars = 50 µm.

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  Fig. 3 Immunohistochemistry for Ki67 in the dentate gyrus of ZLC (A and B), ZLC-Al (C and D), ZDF (E and F), and ZDF-Al (G and H) groups. Ki67-immunoreactive nuclei were observed in the subgranular zone (arrows) of the dentate gyrus. Note that Ki67-immunoreactive nuclei are decreased in the ZLC-Al and ZDF-Al groups compared to the ZLC and ZDF groups, respectively. The lowest number of Ki67-immunoreactive nuclei was observed in the ZDF-Al group. (I) Relative mean number of Ki67-positive nuclei per section in all groups vs. ZLC group (n = 5 per group; *p < 0.05, indicates a significant difference between ZLC and ZDF or ZLC-AL and ZDF-AL, †p < 0.05, indicates a significant difference between ZLC and ZLC-AL or ZDF and ZDF-AL). Error bars indicate the means ± SEM. Scale bars = 100 µm (A, C, E and G), 25 µm (B, D, F and H). GCL, granule cell layer; PL, polymorphic layer; ML, molecular layer.

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  Fig. 4 Immunohistochemistry for DCX in the dentate gyrus of ZLC (A and B), ZLC-Al (C and D), ZDF (E and F), and ZDF-Al (G and H) groups. DCX-immunoreactive neuroblasts are observed in the subgranular zone (arrows) of the dentate gyrus. Note that DCX-immunoreactive neuroblasts were decreased in the ZLC-Al and ZDF-Al groups compared to the ZLC and ZDF groups, respectively. The lowest number of DCX-immunoreactive neuroblasts was observed in the ZDF-Al group. Scale bars = 100 µm (A, C, E and G), 25 µm (B, D, F and H).

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  Fig. 5 Relative optical density (ROD) demonstrated as percentages of ZLC in DCX immunoreactivity (A), mean number of DCX-immunoreactive neuroblasts (B) and the length of neuroblast dendrites (C) in all groups (n = 5 per group; n = 5 per group; *p< 0.05, indicates a significant difference between ZLC and ZDF or ZLC-AL and ZDF-AL, †p < 0.05, indicates a significant difference between ZLC and ZLC-AL or ZDF and ZDF-AL). Error bars indicate the means ± SEM.

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