کد مقاله کد نشریه سال انتشار مقاله انگلیسی ترجمه فارسی نسخه تمام متن
2564618 1561022 2017 7 صفحه PDF سفارش دهید دانلود رایگان
عنوان انگلیسی مقاله ISI
Endocannabinoid dysregulation in cognitive and stress-related brain regions in the Nrg1 mouse model of schizophrenia
ترجمه فارسی عنوان
اختلال در نظم اندوکانابینوئید در مناطق شناختی و مربوط به استرس مغز در مدل NRG1 موس اسکیزوفرنی
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موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی روانپزشکی بیولوژیکی
چکیده انگلیسی


• Chronic adolescent stress increased anandamide levels in the amygdala of mice.
• Nrg1 hypomorphism increased anandamide levels in the amygdala of mice.
• Nrg1 hypomorphism increased 2-AG levels in the hippocampus and reduced levels of 2-AG in the hypothalamus of mice.
• Nrg1 HET mice display impaired spatial learning as measured by the Morris Water Maze.

The endocannabinoid system is dysregulated in schizophrenia. Mice with heterozygous deletion of neuregulin 1 (Nrg1 HET mice) provide a well-characterised animal model of schizophrenia, and display enhanced sensitivity to stress and cannabinoids during adolescence. However, no study has yet determined whether these mice have altered brain endocannabinoid concentrations. Nrg1 application to hippocampal slices decreased 2-arachidonoylglycerol (2-AG) signalling and disrupted long-term depression, a form of synaptic plasticity critical to spatial learning. Therefore we specifically aimed to examine whether Nrg1 HET mice exhibit increased 2-AG concentrations and disruption of spatial learning. As chronic stress influences brain endocannabinoids, we also sought to examine whether Nrg1 deficiency moderates adolescent stress-induced alterations in brain endocannabinoids. Adolescent Nrg1 HET and wild-type (WT) mice were submitted to chronic restraint stress and brain endocannabinoid concentrations were analysed. A separate cohort of WT and Nrg1 HET mice was also assessed for spatial learning performance in the Morris Water Maze. Partial genetic deletion of Nrg1 increased anandamide concentrations in the amygdala and decreased 2-AG concentrations in the hypothalamus. Further, Nrg1 HET mice exhibited increased 2-AG concentrations in the hippocampus and impaired spatial learning performance. Chronic adolescent stress increased anandamide concentrations in the amygdala, however, Nrg1 disruption did not influence this stress-induced change. These results demonstrate for the first time in vivo interplay between Nrg1 and endocannabinoids in the brain. Our results demonstrate that aberrant Nrg1 and endocannabinoid signalling may cooperate in the hippocampus to impair cognition, and that Nrg1 deficiency alters endocannabinoid signalling in brain stress circuitry.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Progress in Neuro-Psychopharmacology and Biological Psychiatry - Volume 72, 4 January 2017, Pages 9–15
نویسندگان
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