Stage-specific modulation of neprilysin and aminopeptidase N in the limbic system during kindling progression

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 n...

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Published inJournal of molecular neuroscience Vol. 33; no. 3; pp. 252 - 261
Main Authors de Gortari, Patricia, Vargas, Miguel Angel, Martínez, Adrián, García-Vázquez, Arlene I, Uribe, Rosa María, Chávez-Gutiérrez, Lucía, Magdaleno, Víctor, Boileau, Guy, Charlí, Jean-Louis, Joseph-Bravo, Patricia
Format Journal Article
LanguageEnglish
Published United States Springer Nature B.V 01.11.2007
Subjects
Animals
CD13 Antigens - genetics
CD13 Antigens - metabolism
Electric Stimulation
In Situ Hybridization
Kindling, Neurologic - physiology
Limbic System - physiology
Male
Neprilysin - genetics
Neprilysin - metabolism
Rats
Rats, Wistar
Rodents
Online AccessGet full text

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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.
AbstractList 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.
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.[PUBLICATION ABSTRACT]
Author Vargas, Miguel Angel
Magdaleno, Víctor
Martínez, Adrián
Boileau, Guy
Chávez-Gutiérrez, Lucía
Joseph-Bravo, Patricia
de Gortari, Patricia
García-Vázquez, Arlene I
Charlí, Jean-Louis
Uribe, Rosa María
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crossref_primary_10_1007_s12031_012_9823_4
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Snippet Aminopeptidase N (APN) and neprilysin (NEP) inactivate neuropeptides released into the brain extracellular fluid. We previously showed that the expression of...
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pubmed
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Index Database
StartPage 252
SubjectTerms Animals
CD13 Antigens - genetics
CD13 Antigens - metabolism
Electric Stimulation
In Situ Hybridization
Kindling, Neurologic - physiology
Limbic System - physiology
Male
Neprilysin - genetics
Neprilysin - metabolism
Rats
Rats, Wistar
Rodents
Title Stage-specific modulation of neprilysin and aminopeptidase N in the limbic system during kindling progression
URI https://www.ncbi.nlm.nih.gov/pubmed/17952634
https://www.proquest.com/docview/881657910
https://search.proquest.com/docview/21313900
https://search.proquest.com/docview/68416579
Volume 33
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