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Increased Expression of Brain-Derived Neurotrophic Factor Transcripts I and VI, cAMP Response Element Binding, and Glucocorticoid Receptor in the Cortex of Patients with Temporal Lobe Epilepsy

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Abstract

A body of evidence supports a relevant role of brain-derived neurotrophic factor (BDNF) in temporal lobe epilepsy (TLE). Magnetic resonance data reveal that the cerebral atrophy extends to regions that are functionally and anatomically connected with the hippocampus, especially the temporal cortex. We previously reported an increased expression of BDNF messenger for the exon VI in the hippocampus of temporal lobe epilepsy patients compared to an autopsy control group. Altered levels of this particular transcript were also associated with pre-surgical use of certain psychotropic. We extended here our analysis of transcripts I, II, IV, and VI to the temporal cortex since this cerebral region holds intrinsic communication with the hippocampus and is structurally affected in patients with TLE. We also assayed the cyclic adenosine monophosphate response element-binding (CREB) and glucocorticoid receptor (GR) genes as there is experimental evidence of changes in their expression associated with BDNF and epilepsy. TLE and pre-surgical pharmacological treatment were considered as the primary clinical independent variables. Transcripts BDNF I and BDNF VI increased in the temporal cortex of patients with pharmacoresistant TLE. The expression of CREB and GR expression follow the same direction. Pre-surgical use of selective serotonin reuptake inhibitors, carbamazepine (CBZ) and valproate (VPA), was associated with the differential expression of specific BDNF transcripts and CREB and GR genes. These changes could have functional implication in the plasticity mechanisms related to temporal lobe epilepsy.

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Acknowledgements

This article constitutes a partial requisite to obtain the Ph.D. grade in the postgraduate program of Biological Sciences at the National Autonomous University of Mexico (UNAM) for GAM-L. This study was supported the research fund of the National Institute of Psychiatry “Ramón de la Fuente Muñíz” Project IC142040.0. We would like to thank Jose Perez Luna for his technical help.

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Authors and Affiliations

  1. Department of Genetics, National Institute of Psychiatry “Ramón de la Fuente Muñiz” (INPRFM), Mexico City, Mexico

    G. A. Martínez-Levy, F. Rodríguez-Pineda, A. Nani, M. Briones-Velasco & C. S. Cruz-Fuentes

  2. Department of Pharmacobiology, Center for Research and Advanced Studies, CINVESTAV, Mexico City, Mexico

    L. Rocha

  3. Neurosurgery Section, National Institute of Neurology and Neurosurgery “Manuel Velasco Suárez” (INNNMVS), Mexico City, Mexico

    M. A. Alonso-Vanegas, R. M. Buentello-García & J. Cienfuegos

  4. Clinical Research Department, National Institute of Neurology and Neurosurgery “Manuel Velasco Suárez” (INNNMVS), Mexico City, Mexico

    D. San-Juan

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  1. G. A. Martínez-Levy
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  2. L. Rocha
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  9. J. Cienfuegos
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  10. C. S. Cruz-Fuentes
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Correspondence to C. S. Cruz-Fuentes.

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All experiments were approved by the Ethics Committee of the National Institute of Neurology and Neurosurgery “Manuel Velasco Suarez” (INNNMVS) in Mexico City (project 70/12). Participants signed an informed consent.

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Martínez-Levy, G., Rocha, L., Rodríguez-Pineda, F. et al. Increased Expression of Brain-Derived Neurotrophic Factor Transcripts I and VI, cAMP Response Element Binding, and Glucocorticoid Receptor in the Cortex of Patients with Temporal Lobe Epilepsy. Mol Neurobiol 55, 3698–3708 (2018). https://doi.org/10.1007/s12035-017-0597-0

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