کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6273936 | 1614815 | 2014 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Increased dopaminergic innervation in the brain of conditional mutant mice overexpressing Otx2: Effects on locomotor behavior and seizure susceptibility
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کلمات کلیدی
OTX25-HTIEGGAD65VGLUT2VTADATGCLMPTPkainic acid - اسید کرییکDopamine transporter - انتقال دهنده دوپامینEpilepsy - بیماری صرعanalysis of variance - تحلیل واریانسANOVA - تحلیل واریانس Analysis of variancesubstantia nigra - توده سیاهtyrosine hydroxylase - تیروزین هیدروکسیلازvesicular glutamate transporter 2 - حمل کننده گلوتامات vesicular 2limbic system - دستگاه کنارهای، سیستم لیمبیکDopamine - دوپامینSerotonin - سروتونینprefrontal cortex - قشر prefrontalventral tegmental area - ناحیه تگمنتوم شکمیEEG - نوار مغزیHippocampus - هیپوکامپ Parvalbumin - پاروالبومینimmediate early gene - ژن فوری اولیه
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
The homeobox-containing transcription factor Otx2 controls the identity, fate and proliferation of mesencephalic dopaminergic (mesDA) neurons. Transgenic mice, in which Otx2 was conditionally overexpressed by a Cre recombinase expressed under the transcriptional control of the Engrailed1 gene (En1Cre/+; tOtx2ov/+), show an increased number of mesDA neurons during development. In adult mice, Otx2 is expressed in a subset of neurons in the ventral tegmental area (VTA) and its overexpression renders mesDA more resistant to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-HCl (MPTP) neurotoxin. Here we further investigated the neurological consequences of the increased number of mesDA neurons in En1Cre/+; tOtx2ov/+ adult mice. Immunohistochemistry for the active, glycosylated form of the dopamine transporter (glyco-Dat) showed that En1Cre/+; tOtx2ov/+ adult mice display an increased density of mesocortical DAergic fibers, as compared to control animals. Increased glyco-Dat staining was accompanied by a marked hypolocomotion in En1Cre/+; tOtx2ov/+ mice, as detected in the open field test. Since conditional knockout mice lacking Otx2 in mesDA precursors (En1Cre/+; Otx2floxv/flox mice) show a marked resistance to kainic acid (KA)-induced seizures, we investigated the behavioral response to KA in En1Cre/+; tOtx2ov/+ and control mice. No difference was observed between mutant and control mice, but En1Cre/+; tOtx2ov/+ mice showed a markedly different c-fos mRNA induction profile in the cerebral cortex and hippocampus after KA seizures, as compared to controls. Accordingly, an increased density of parvalbumin (PV)-positive inhibitory interneurons was detected in the deep layers of the frontal cortex of naïve En1Cre/+; tOtx2ov/+ mice, as compared to controls. These data indicate that Otx2 overexpression results in increased DAergic innervation and PV cell density in the fronto-parietal cortex, with important consequences on spontaneous locomotor activity and seizure-induced gene expression. Our results strengthen the notion that Otx2 mutant mouse models are a powerful genetic tool to unravel the molecular and behavioral consequences of altered development of the DAergic system.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 261, 7 March 2014, Pages 173-183
Journal: Neuroscience - Volume 261, 7 March 2014, Pages 173-183
نویسندگان
P.P. Tripathi, L.G. Di Giovannantonio, E. Sanguinetti, D. Acampora, M. Allegra, M. Caleo, W. Wurst, A. Simeone, Y. Bozzi,