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Down regulation of the Proliferation and Apoptotic Pathways in the Embryonic Brain of Diabetic Rats

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Abstract

Compelling evidence shows that the offspring subjected to uncontrolled hyperlycemia during gestation display behavioral, neurochemical, and cellular abnormalities during adulthood. However, the molecular mechanisms underlying these defects remain elusive. Previous studies have shown an increased rate of apoptosis and a decreased index of neuronal proliferation associated with diabetic embryopathy. The aim of the present study was to determine whether impairments in apoptotic related proteins also occur in the developing central nervous system from non-malformed embryos exposed to uncontrolled gestational hyperglycemia. Pregnant rats injected with either streptozotocin or vehicle were killed on gestational day 19. Offspring brains were quickly removed to evaluate protein expression by Western blotting. Embryonic brains from diabetic rats exhibited a decrease in the cell survival p-Akt expression (52.83 ± 24.35%) and in the pro-apoptotic protein Bax (56.16 ± 6.47%). Moreover, the anti-apoptotic protein Bcl-2 showed a non-significant increase while there were no changes in Procaspase 3 or cleaved Caspase 3 proteins. The cytoskeleton proteins NF-200 and GFAP were also examined. Neither NF-200 nor GFAP showed differences in embryonic brains from diabetic rats compared to controls. Altogether, these results indicate that both proliferation and apoptotic pathways are decreased in the brain from the developing offspring of diabetic rats. Since selective neuronal apoptosis, as well as selective cell proliferation, are specifically involved in brain organogenesis, it is possible that simultaneous impairments during the perinatal period contribute to the long lasting alterations observed in the adult brain.

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Acknowledgments

This study was partially supported by grants from the University of Buenos Aires (UBACYT, M012), and the Consejo Nacional de Investigaciones Científicas y Técnicas de la República Argentina (CONICET, PIP860), J B. was supported by CONICET fellowship.

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Authors and Affiliations

  1. Laboratorio de Neurobiología, Instituto de Biología y Medicina Experimental, Vuelta de Obligado 2490, C1428ADN, Ciudad Autónoma de Buenos Aires, Argentina

    María Sol Kruse, Joaquín Barutta, María Cristina Vega & Héctor Coirini

  2. Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, 5to Piso, C1121ABG, Ciudad Autónoma de Buenos Aires, Argentina

    Héctor Coirini

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  1. María Sol Kruse
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  2. Joaquín Barutta
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  3. María Cristina Vega
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  4. Héctor Coirini
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Correspondence to Héctor Coirini.

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María Sol Kruse and Joaquín Barutta contributed equally to this study.

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Kruse, M.S., Barutta, J., Vega, M.C. et al. Down regulation of the Proliferation and Apoptotic Pathways in the Embryonic Brain of Diabetic Rats. Cell Mol Neurobiol 32, 1031–1037 (2012). https://doi.org/10.1007/s10571-012-9820-8

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  • DOI: https://doi.org/10.1007/s10571-012-9820-8

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