Human Brain Slice Culture: A Useful Tool to Study Brain Disorders and Potential Therapeutic Compounds
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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.
KeywordsAlzheimer’s disease Brain bank Brain-derived neurotrophic factor Depression Electrical activity Human brain slice culture Neuropsychiatric disorders Organotypic culture Postmortem human brain tissue Resected human brain tissue
We are grateful to the Netherlands Brain Bank (Director Dr. I. Huitinga) at the Netherlands Institute for Neuroscience for providing brain material and patient information, and to Wilma Verweij for secretarial assistance. This review was supported by the National Natural Science Foundation of China (81501172), the China Exchange Programme of the Royal Netherlands Academy of Arts and Sciences (10CDP0037 and 05CD9027), the Shanghai Municipal Commission of Health and Family Planning (20154Y0016), an Innovation Project of the Chinese Academy of Sciences (KSCX2-SW-217), a National Basic Research Development Program of China (2006CB500705), the Internationale Stichting Alzheimer Onderzoek (05501), the Jan Dekkerstichting and dr. Lutgardine Bouwmanstichting, and the Stichting Vrienden van het Herseninstituut.
Conflict of interest
The authors declare that there is no conflict of interest.
- 10.Van Dam D, De Deyn PP. Non human primate models for Alzheimer’s disease-related research and drug discovery. Expert Opin Drug Discov 2017, 12: 187–200.Google Scholar
- 15.Shahani N, Subramaniam S, Wolf T, Tackenberg C, Brandt R. Tau aggregation and progressive neuronal degeneration in the absence of changes in spine density and morphology after targeted expression of Alzheimer’s disease-relevant tau constructs in organotypic hippocampal slices. J Neurosci 2006, 26: 6103–6114.CrossRefGoogle Scholar
- 17.Molnar G, Rozsa M, Baka J, Holderith N, Barzo P, Nusser Z, et al. Human pyramidal to interneuron synapses are mediated by multi-vesicular release and multiple docked vesicles. Elife 2016, 5.Google Scholar
- 41.Schwarz N, Hedrich UBS, Schwarz H, P AH, Dammeier N, Auffenberg E, et al. Human cerebrospinal fluid promotes long-term neuronal viability and network function in human neocortical organotypic brain slice cultures. Sci Rep 2017, 7: 12249.Google Scholar
- 49.Andersson M, Avaliani N, Svensson A, Wickham J, Pinborg LH, Jespersen B, et al. Optogenetic control of human neurons in organotypic brain cultures. Sci Rep 2016, 6.Google Scholar