1.Human Brain Slice Culture: A Useful Tool to Study Brain Disorders and Potential Therapeutic Compounds.
Xin-Rui QI ; Ronald W H VERWER ; Ai-Min BAO ; Rawien A BALESAR ; Sabina LUCHETTI ; Jiang-Ning ZHOU ; Dick F SWAAB
Neuroscience Bulletin 2019;35(2):244-252
Investigating the pathophysiological mechanisms underlying brain disorders is a priority if novel therapeutic strategies are to be developed. In vivo studies of animal models and in vitro studies of cell lines/primary cell cultures may provide useful tools to study certain aspects of brain disorders. However, discrepancies among these studies or unsuccessful translation from animal/cell studies to human/clinical studies often occur, because these models generally represent only some symptoms of a neuropsychiatric disorder rather than the complete disorder. Human brain slice cultures from postmortem tissue or resected tissue from operations have shown that, in vitro, neurons and glia can stay alive for long periods of time, while their morphological and physiological characteristics, and their ability to respond to experimental manipulations are maintained. Human brain slices can thus provide a close representation of neuronal networks in vivo, be a valuable tool for investigation of the basis of neuropsychiatric disorders, and provide a platform for the evaluation of novel pharmacological treatments of human brain diseases. A brain bank needs to provide the necessary infrastructure to bring together donors, hospitals, and researchers who want to investigate human brain slices in cultures of clinically and neuropathologically well-documented material.
Brain
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drug effects
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physiopathology
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Brain Diseases
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drug therapy
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physiopathology
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Humans
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Tissue Culture Techniques
2.Quantification of Tyrosine Hydroxylase and ErbB4 in the Locus Coeruleus of Mood Disorder Patients Using a Multispectral Method to Prevent Interference with Immunocytochemical Signals by Neuromelanin.
Lei GUO ; Jochem STORMMESAND ; Zheng FANG ; Qingbin ZHU ; Rawien BALESAR ; Joop VAN HEERIKHUIZE ; Arja SLUITER ; Dick SWAAB ; Ai-Min BAO
Neuroscience Bulletin 2019;35(2):205-215
The locus coeruleus (LC) has been studied in major depressive disorder (MDD) and bipolar disorder (BD). A major problem of immunocytochemical studies in the human LC is interference with the staining of the immunocytochemical end-product by the omnipresent natural brown pigment neuromelanin. Here, we used a multispectral method to untangle the two colors: blue immunocytochemical staining and brown neuromelanin. We found significantly increased tyrosine hydroxylase (TH) in the LC of MDD patients-thus validating the method-but not in BD patients, and we did not find significant changes in the receptor tyrosine-protein kinase ErbB4 in the LC in MDD or BD patients. We observed clear co-localization of ErbB4, TH, and neuromelanin in the LC neurons. The different stress-related molecular changes in the LC may contribute to the different clinical symptoms in MDD and BD.
Aged
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Aged, 80 and over
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Bipolar Disorder
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metabolism
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pathology
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Depressive Disorder, Major
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metabolism
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pathology
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Female
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Humans
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Image Processing, Computer-Assisted
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Immunohistochemistry
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methods
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Locus Coeruleus
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metabolism
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pathology
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Male
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Melanins
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metabolism
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Microscopy
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methods
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Middle Aged
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Neurons
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metabolism
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pathology
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Receptor, ErbB-4
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metabolism
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Sensitivity and Specificity
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Spectrum Analysis
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methods
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Tyrosine 3-Monooxygenase
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metabolism