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Stage-specific Modulation of Neprilysin and Aminopeptidase N in the Limbic System During Kindling Progression

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Abstract

Aminopeptidase N (APN) and neprilysin (NEP) inactivate neuropeptides released into the brain extracellular fluid. We previously showed that the expression of pyroglutamyl peptidase II (PPII), the TRH degrading ecto-enzyme, is regulated in rat brain by amygdaline kindling, a paradigm that activates neuronal pathways in the limbic system increasing the expression of several neuropeptides including TRH and opioids. To understand the specificity of this phenomenon, we studied APN and NEP expression in brains of partially or fully kindled rats (stage II and V), sacrificed 6 h after last stimulus, compared with sham-operated animals. In situ hybridization analysis of NEP mRNA levels showed decreased expression at stage II in CA1, CA2, olfactory tubercle and medial mammillary nucleus, and increased at stage V in CA1 and CA2 cells. These changes were specific for the ipsilateral side. APN mRNA levels, semi-quantified by RT-PCR, were decreased at stage II and increased at stage V, in frontal cortex-olfactory tubercle, and hippocampus. NEP and APN enzymatic activities, determined by fluorometric assays, followed similar variations to their respective mRNA levels. The coordinated changes (in some regions) of NEP and APN expression were opposite to those previously observed for PPII mRNA and activity levels in limbic regions. These results demonstrate that expression of ectopeptidases can be regulated when peptide neurons are activated and, that regulation is enzyme-, region-, and stage-specific.

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Authors and Affiliations

  1. Div. Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñíz, México D.F., México

    Patricia de Gortari, Adrián Martínez & Víctor Magdaleno

  2. Dept. Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Ave. Universidad 2001, Chamilpa, Cuernavaca, Morelos, 62210, México

    Miguel Angel Vargas, Arlene I. García-Vázquez, Rosa María Uribe, Lucía Chávez-Gutiérrez, Jean-Louis Charlí & Patricia Joseph-Bravo

  3. Dept. Biochimie, Université de Montreal, Montreal, Canada

    Guy Boileau

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  1. Patricia de Gortari
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  2. Miguel Angel Vargas
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  10. Patricia Joseph-Bravo
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de Gortari, P., Vargas, M.A., Martínez, A. et al. Stage-specific Modulation of Neprilysin and Aminopeptidase N in the Limbic System During Kindling Progression. J Mol Neurosci 33, 252–261 (2007). https://doi.org/10.1007/s12031-007-0020-9

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