ABSTRACT
Parkinson's disease (PD) is a basal ganglia movement disorder characterized by progressive degeneration of the nigrostriatal dopaminergic system. Immunohistochemical methods have been widely used for characterization of dopaminergic neuronal injury in animal models of PD, including the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model. However, conventional immunohistochemical techniques applied to tissue sections have inherent limitations with respect to loss of 3D resolution, yielding insufficient information on the architecture of the dopaminergic system. To provide a more comprehensive and non-biased map of MPTP-induced changes in central dopaminergic pathways, we used iDISCO immunolabeling, light-sheet fluorescence microscopy (LSFM) and deep-learning computational methods for whole-brain three-dimensional visualization and automated quantitation of tyrosine hydroxylase (TH)-positive neurons in the adult mouse brain. Mice terminated 7 days after acute MPTP administration demonstrated widespread alterations in TH expression. Compared to vehicle controls, MPTP-dosed mice showed a significant loss of TH-positive neurons in the substantia nigra pars compacta and ventral tegmental area. Also, MPTP dosing reduced overall TH signal intensity in basal ganglia nuclei, i.e. the substantia nigra, caudate-putamen, globus pallidus and subthalamic nucleus. In contrast, increased TH signal intensity was predominantly observed in limbic regions, including several subdivisions of the amygdala and hypothalamus. In conclusion, mouse whole-brain 3D imaging is ideal for unbiased automated counting and densitometric analysis of TH-positive cells. The LSFM-deep learning pipeline tracked brain-wide changes in catecholaminergic pathways in the MPTP mouse model of PD, and may be applied for preclinical characterization of compounds targeting dopaminergic neurotransmission.
Subject(s)
Brain/diagnostic imaging , Disease Models, Animal , Imaging, Three-Dimensional/methods , Neurons/enzymology , Parkinson Disease/diagnostic imaging , Tyrosine 3-Monooxygenase/analysis , Animals , Deep Learning , MPTP Poisoning/diagnostic imaging , Mice , Microscopy, Fluorescence , Motor Skills , Parkinson Disease/enzymologyABSTRACT
BACKGROUND: We assumed that persons with a Russian/Soviet cultural background have a more skeptical attitude towards psychotherapy than persons with a German background because of the poor distribution of psychotherapy and the knowledge about this kind of treatment in Russia. METHODS: We compared the views of Russian probands (n=40), Russian migrants living in Germany (n=65) and German probands (n=70) with the "Questionnaire on Attitudes towards Psychotherapeutic Treatment" (QAPT). For the study of the Russian probands we translated the questionnaire into the Russian language. RESULTS: The psychometric examination predominantly suggests the quality of the Russian version of the QAPT. Russian probands showed a more skeptical attitude towards psychotherapy compared to the German probands. The migrants had a tendentially more negative attitude than the Germans and a more positive attitude than the Russians. However, we could not determine any differences concerning the anticipated social acceptance regarding participation in psychotherapy. DISCUSSION: The results suggest the relevance of culture-specific factors in psychotherapy and an increased need for information of persons with a Russian/Soviet cultural background about psychotherapy.
