6-Hydroxydopamine leads to T2 hyperintensity, decreased claudin-3 immunoreactivity and altered aquaporin 4 expression in the striatum

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• 作者：Britta Wachter^a ; ^b ; ¹ ; ^{Wachter@anatu.uni-tuebingen.de} ; Sonja Schü ; rger^c ; ^d ; ¹ ; ^{sonja.schuerger@google.com} ; Andreas Schmid^e ; ^{A.Schmid@med.uni-tuebingen.de} ; Adriane Gr&ouml ; ger^d ; ^{adriane.groeger@med.uni-tuebingen.de} ; Rü ; diger Sadler^c ; ^{ruedigersadler@web.de} ; Anna Speidel^a ; ^{anna.speidel@gmx.de} ; Jens Rolinger^c ; ^d ; ^{j.rolinger@t-online.de} ; Bernd J. Pichler^e ; ^{Bernd.Pichler@med.uni-tuebingen.de} ; Daniela Berg^d ; ^{daniela.berg@uni-tuebingen.de} ; Hans-Joachim Wagner^a ; ^{hjwagner@anatu.uni-tuebingen.de} ; Andreas von Ameln-Mayerhofer^c ; ^{andreas.mayerhofer@uni-tuebingen.de} ; Eva Kü ; ppers^a ; ^{kueppers@anatu.uni-tuebingen.de}
• 关键词：6-OHDA ; 6-hydroxydopamine ; AQP4 ; aquaporin 4 ; BBB ; blood brain barrier ; CNS ; central nervous system ; GFAP ; glial fibrillary acidic protein ; MRI ; magnetic resonance imaging ; OAP ; orthogonal array of particles ; PD ; Parkinson's disease ; ROI ; region of intere
• 刊名：Behavioural Brain Research
• 出版年：2012
• 期刊代码：3_01664328
• 类别：neu
• 出版时间：15 June, 2012
• 卷：232
• 期：1
• 页码：148-158
• 文件大小：2439 K

摘要

The neurotoxin 6-hydroxydopamine (6-OHDA) is frequently used in animal models to mimic Parkinson's disease. Imaging studies describe hyperintense signalling in regions close to the site of the 6-OHDA injection in T2-weighted (T2w) magnetic resonance imaging (MRI). The nature of this hyperintense signal remains elusive and still is matter of discussion. Here we demonstrate hyperintense signalling in T2w MRI and decreased apparent diffusion coefficient (ADC) values following intraventricular injection of 6-OHDA. Moreover, we show decreased GFAP immunoreactivity in brain regions corresponding to the region revealing the hyperintense signalling, probably indicating a loss of astrocytes due to a toxic effect of 6-OHDA.

In the striatum, where no hyperintense signalling in MRI was observed following intraventricular 6-OHDA injection, immunohistochemical and molecular analyses revealed an altered expression of the water channel aquaporin 4 and the emergence of vasogenic edema, indicated by an increased perivascular space. Moreover, a significant decrease of claudin-3 immunoreactivity was observed, implying alterations in the blood brain barrier.

These findings indicate that intraventricular injection of 6-OHDA results (1) in effects close to the ventricles that can be detected as hyperintense signalling in T2w MRI accompanied by reduced ADC values and (2) in effects on brain regions not adjacent to the ventricles, where a disturbance of water homeostasis occurs. We clearly demonstrate that 6-OHDA leads to brain edema that in turn may affect the overall results of experiments (e.g. behavioral alterations). Therefore, when using 6-OHDA in Parkinson's models effects that are not mediated by degeneration of catecholaminergic neurons have to be considered.