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Epigenetic Mechanisms Regulating Neural Plasticity

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Front. Cell. Neurosci. | doi: 10.3389/fncel.2018.00103

Ovarian function modulates the effects of long-chain polyunsaturated fatty acids on the mouse cerebral cortex

 Jose Luis Herrera1, Lara Ordóñez-Gutiérrez2,  Gemma Fabrias3, Josefina Casas3, Araceli Morales3, Guadalberto Hernandez1, Nieves G. Acosta4,  COVADONGA RODRÍGUEZ4, Luis Prieto-Valiente5,  Luis M. Garcia-Segura6,  Rafael Alonso1 and  Francisco G. Wandosell2*
  • 1Departamento de Ciencias Médicas Básica and Instituto de Tecnologías Biomédicas (ITB), Centro de Investigaciones Biomédicas de Canarias (CIBICAN), Spain
  • 2Molecular Neurobiology, Centro de Biología Molecular Severo Ochoa (CSIC), Spain
  • 3(IQAC-CSIC),, Institute of Advanced Chemistry of Catalonia (CSIC), Spain
  • 4Departamento de Biología Animal, Edafología y Geología, Universidad de La Laguna, Spain
  • 5Universidad Católica ,, Universidad de Murcia, Spain
  • 6& Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Cajal Institute (CSIC), Spain

Different dietary ratios of n-6/n-3 long-chain polyunsaturated fatty acids (LC-PUFAs) may alter brain lipid profile, neural activity and brain cognitive function. To determine whether ovarian hormones influence the effect of diet on the brain, ovariectomized and sham-operated mice continuously treated with placebo or estradiol were fed for three months with diets containing low or high n-6/n-3 LC-PUFA ratios. The fatty acid (FA) profile and expression of key neuronal proteins were analyzed in the cerebral cortex, with intact female mice on standard diet serving as internal controls of brain lipidome composition. Diets containing different concentrations of LC-PUFAs greatly modified total FAs, sphingolipids and gangliosides in the cerebral cortex. Some of these changes were dependent on ovarian hormones, as they were not detected in ovariectomized animals, and in the case of complex lipids, the effect of ovariectomy was partially or totally reversed by continuous administration of estradiol. However, even though differential dietary LC-PUFA content modified the expression of neuronal proteins such as synapsin and its phosphorylation level, PSD-95, amyloid precursor protein (APP) or glial proteins such as glial fibrillary acidic protein (GFAP), an effect also dependent on the presence of the ovary, chronic estradiol treatment was unable to revert the dietary effects on brain cortex synaptic proteins. These results suggest that, in addition to stable estradiol levels, other ovarian hormones such as progesterone and/or cyclic ovarian secretory activity could play a physiological role in the modulation of dietary LC-PUFAs on the cerebral cortex, which may have clinical implications for post-menopausal women on diets enriched with different proportions of n-3 and n-6 LC-PUFAs.

Keywords: Cerebral cortex lipidome, Long-chain polyunsaturated fatty acids (LC-PUFAs), Docosahexaenoic acid (DHA), Sphingolipids, Ovarian hormones, Synaptic proteins

Received: 28 Nov 2017; Accepted: 29 Mar 2018.

Edited by:

Merce Pallas, Universitat de Barcelona, Spain

Reviewed by:

Amy Christensen, University of Southern California, United States
Mustapha U. Imam, Zhengzhou University, China  

Copyright: © 2018 Herrera, Ordóñez-Gutiérrez, Fabrias, Casas, Morales, Hernandez, Acosta, RODRÍGUEZ, Prieto-Valiente, Garcia-Segura, Alonso and Wandosell. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Francisco G. Wandosell, Centro de Biología Molecular Severo Ochoa (CSIC), Molecular Neurobiology, Unv Autonoma de Madrid, (UAM-CSIC & CIBERNED), C/Nicolas Cabrera, Cantoblanco, Madrid, Madrid, 28049, Spain,