Stage-specific modulation of neprilysin and aminopeptidase N in the limbic system during kindling progression
Por:
De Gortari P., Vargas M.A., Martínez A., García-Vázquez A.I., Uribe R.M., Chávez-Gutiérrez L., Magdaleno V., Boileau G., Charlí J.-L., Joseph-Bravo P.
Publicada:
1 ene 2007
Categoría:
Cellular and Molecular Neuroscience
Resumen:
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. © Humana Press Inc. 2007.
Filiaciones:
De Gortari P.:
Div. Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñíz, México D.F., Mexico
Vargas M.A.:
Dept. Genética del Desarrollo Y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Ave. Universidad 2001, Chamilpa, Cuernavaca, Morelos, 62210, Mexico
Martínez A.:
Div. Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñíz, México D.F., Mexico
García-Vázquez A.I.:
Dept. Genética del Desarrollo Y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Ave. Universidad 2001, Chamilpa, Cuernavaca, Morelos, 62210, Mexico
Uribe R.M.:
Dept. Genética del Desarrollo Y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Ave. Universidad 2001, Chamilpa, Cuernavaca, Morelos, 62210, Mexico
Chávez-Gutiérrez L.:
Dept. Genética del Desarrollo Y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Ave. Universidad 2001, Chamilpa, Cuernavaca, Morelos, 62210, Mexico
Magdaleno V.:
Div. Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñíz, México D.F., Mexico
Boileau G.:
Dept. Biochimie, Université de Montreal, Montreal, Que., Canada
Charlí J.-L.:
Dept. Genética del Desarrollo Y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Ave. Universidad 2001, Chamilpa, Cuernavaca, Morelos, 62210, Mexico
Joseph-Bravo P.:
Dept. Genética del Desarrollo Y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Ave. Universidad 2001, Chamilpa, Cuernavaca, Morelos, 62210, Mexico
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