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Protection by DHA of Early Hippocampal Changes in Diabetes: Possible Role of CREB and NF-κB

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Abstract

The mechanisms underlying diabetic encephalopathy, are only partially understood. In this study, we try to address the mechanisms of diabetes induced damage and whether docosahexaenoic acid (DHA) could attenuate the degenerative changes in diabetic hippocampus in a rodent model of diabetes. Diabetes was induced in rats by an intraperitoneal injection of streptozotocin. Animals were divided into the following experimental groups: control rats; control animals treated with DHA; untreated diabetic rats; diabetic rats treated with insulin; diabetic rats treated with DHA; diabetic rats treated with insulin and DHA. At the end of week 12, rats were killed and one of the hemispheres was cryosectioned and the other was dissected and hippocampi homogenized. The number of bromodeoxyuridine positive cells in the hippocampus of diabetic rats was decreased, and the latency time to find the platform in the Morris Water maze was significantly increased in the diabetic rats when compared to controls. No changes where observed in the expression of p21 in the hippocampus of control and diabetic rats. Biochemical markers of oxidative stress were altered in hippocampus of diabetic rats, and NFκB-positive cells were increased in the hippocampus of diabetic rats when compared to controls. Treatment with DHA, or the combination of DHA with insulin, significantly restored to control levels all the values mentioned above. Our findings confirm a pivotal role for oxidative stress as well as NF-κB, but not p21, in diabetes-induced hippocampal impairments. Administration of DHA as well as insulin prevented the changes induced by diabetes in hippocampus.

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Acknowledgments

This work was supported in part by Funds from Ministerio de Ciencia e Innovación (SAF 2010-21317) and Copernicus-Santander (PRCEU-UCH/COP(01)10/11) programme of the Universidad CEU—Cardenal Herrera.

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Authors and Affiliations

  1. Department of Fisiología, Farmacología and Toxicología, Universidad CEU Cardenal Herrera, Av. Seminario S/n, 46113, Moncada, Valencia, Spain

    Raquel Alvarez-Nölting & Maria Miranda

  2. Fundación Oftalmológica del Mediterráneo, General Avilés/Pio Baroja, 46015, Valencia, Spain

    Emma Arnal & Francisco J. Romero

  3. Facultad de Medicina, Universidad Católica de Valencia ‘San Vicente Mártir’, Quevedo, 2, 46001, Valencia, Spain

    Jorge M. Barcia & Francisco J. Romero

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  1. Raquel Alvarez-Nölting
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  2. Emma Arnal
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  4. Maria Miranda
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  5. Francisco J. Romero
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Correspondence to Francisco J. Romero.

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Alvarez-Nölting, R., Arnal, E., Barcia, J.M. et al. Protection by DHA of Early Hippocampal Changes in Diabetes: Possible Role of CREB and NF-κB. Neurochem Res 37, 105–115 (2012). https://doi.org/10.1007/s11064-011-0588-x

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  • DOI: https://doi.org/10.1007/s11064-011-0588-x

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