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The Endocannabinoid System across Postnatal Development in Transmembrane Domain Neuregulin 1 Mutant Mice

The use of cannabis is a well-established component risk factor for schizophrenia, particularly in adolescent individuals with genetic predisposition for the disorder. Alterations to the endocannabinoid system have been found in the prefrontal cortex of patients with schizophrenia. Thus, we assessed...

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Autores principales: Chesworth, Rose, Long, Leonora E., Weickert, Cynthia Shannon, Karl, Tim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5808294/
https://www.ncbi.nlm.nih.gov/pubmed/29467679
http://dx.doi.org/10.3389/fpsyt.2018.00011
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author Chesworth, Rose
Long, Leonora E.
Weickert, Cynthia Shannon
Karl, Tim
author_facet Chesworth, Rose
Long, Leonora E.
Weickert, Cynthia Shannon
Karl, Tim
author_sort Chesworth, Rose
collection PubMed
description The use of cannabis is a well-established component risk factor for schizophrenia, particularly in adolescent individuals with genetic predisposition for the disorder. Alterations to the endocannabinoid system have been found in the prefrontal cortex of patients with schizophrenia. Thus, we assessed whether molecular alterations exist in the endocannabinoid signalling pathway during brain development in a mouse model for the schizophrenia risk gene neuregulin 1 (Nrg1). We analysed transcripts encoding key molecules of the endocannabinoid system in heterozygous transmembrane domain Nrg1 mutant mice (Nrg1 TM HET), which is known to have increased sensitivity to cannabis exposure. Tissue from the prelimbic cortex and hippocampus of male and female Nrg1 TM HET mice and wild type-like littermates was collected at postnatal days (PNDs) 7, 10, 14, 21, 28, 35, 49, and 161. Quantitative polymerase chain reaction was conducted to assess mRNA levels of cannabinoid receptor 1 (CB(1)R) and enzymes for the synthesis and breakdown of the endocannabinoid 2-arachidonoylglycerol [i.e., diacylglycerol lipase alpha (DAGLα), monoglyceride lipase (MGLL), and α/β-hydrolase domain-containing 6 (ABHD6)]. No sex differences were found for any transcripts in either brain region; thus, male and female data were pooled. Hippocampal and cortical mRNA expression of DAGLα, MGLL, and ABHD6 increased until PND 21–35 and then decreased and stabilised for the rest of postnatal development. Hippocampal CB(1)R mRNA expression increased until PND 21 and decreased after this age. Expression levels of these endocannabinoid markers did not differ in Nrg1 TM HET compared to control mice at any time point. Here, we demonstrate dynamic changes in the developmental trajectory of several key endocannabinoid system transcripts in the mouse brain, which may correspond with periods of endocannabinoid system maturation. Nrg1 TM HET mutation did not alter the developmental trajectory of the endocannabinoid markers assessed, suggesting that other mechanisms may be responsible for the exaggerated cannabinoid susceptibility in these mice.
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spelling pubmed-58082942018-02-21 The Endocannabinoid System across Postnatal Development in Transmembrane Domain Neuregulin 1 Mutant Mice Chesworth, Rose Long, Leonora E. Weickert, Cynthia Shannon Karl, Tim Front Psychiatry Psychiatry The use of cannabis is a well-established component risk factor for schizophrenia, particularly in adolescent individuals with genetic predisposition for the disorder. Alterations to the endocannabinoid system have been found in the prefrontal cortex of patients with schizophrenia. Thus, we assessed whether molecular alterations exist in the endocannabinoid signalling pathway during brain development in a mouse model for the schizophrenia risk gene neuregulin 1 (Nrg1). We analysed transcripts encoding key molecules of the endocannabinoid system in heterozygous transmembrane domain Nrg1 mutant mice (Nrg1 TM HET), which is known to have increased sensitivity to cannabis exposure. Tissue from the prelimbic cortex and hippocampus of male and female Nrg1 TM HET mice and wild type-like littermates was collected at postnatal days (PNDs) 7, 10, 14, 21, 28, 35, 49, and 161. Quantitative polymerase chain reaction was conducted to assess mRNA levels of cannabinoid receptor 1 (CB(1)R) and enzymes for the synthesis and breakdown of the endocannabinoid 2-arachidonoylglycerol [i.e., diacylglycerol lipase alpha (DAGLα), monoglyceride lipase (MGLL), and α/β-hydrolase domain-containing 6 (ABHD6)]. No sex differences were found for any transcripts in either brain region; thus, male and female data were pooled. Hippocampal and cortical mRNA expression of DAGLα, MGLL, and ABHD6 increased until PND 21–35 and then decreased and stabilised for the rest of postnatal development. Hippocampal CB(1)R mRNA expression increased until PND 21 and decreased after this age. Expression levels of these endocannabinoid markers did not differ in Nrg1 TM HET compared to control mice at any time point. Here, we demonstrate dynamic changes in the developmental trajectory of several key endocannabinoid system transcripts in the mouse brain, which may correspond with periods of endocannabinoid system maturation. Nrg1 TM HET mutation did not alter the developmental trajectory of the endocannabinoid markers assessed, suggesting that other mechanisms may be responsible for the exaggerated cannabinoid susceptibility in these mice. Frontiers Media S.A. 2018-02-07 /pmc/articles/PMC5808294/ /pubmed/29467679 http://dx.doi.org/10.3389/fpsyt.2018.00011 Text en Copyright © 2018 Chesworth, Long, Weickert and Karl. http://creativecommons.org/licenses/by/4.0/ 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.
spellingShingle Psychiatry
Chesworth, Rose
Long, Leonora E.
Weickert, Cynthia Shannon
Karl, Tim
The Endocannabinoid System across Postnatal Development in Transmembrane Domain Neuregulin 1 Mutant Mice
title The Endocannabinoid System across Postnatal Development in Transmembrane Domain Neuregulin 1 Mutant Mice
title_full The Endocannabinoid System across Postnatal Development in Transmembrane Domain Neuregulin 1 Mutant Mice
title_fullStr The Endocannabinoid System across Postnatal Development in Transmembrane Domain Neuregulin 1 Mutant Mice
title_full_unstemmed The Endocannabinoid System across Postnatal Development in Transmembrane Domain Neuregulin 1 Mutant Mice
title_short The Endocannabinoid System across Postnatal Development in Transmembrane Domain Neuregulin 1 Mutant Mice
title_sort endocannabinoid system across postnatal development in transmembrane domain neuregulin 1 mutant mice
topic Psychiatry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5808294/
https://www.ncbi.nlm.nih.gov/pubmed/29467679
http://dx.doi.org/10.3389/fpsyt.2018.00011
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