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- Title
Characterization of three‐dimensional rat central nervous system culture maturation, with applications to monitor cholinergic integrity.
- Authors
Andersen, Parker L.; Vermette, Patrick; Khalil, Abdelouahed; Witkowski, Jacek M.; Fülöp, Tamas
- Abstract
Studying age‐related neuropathologies in vitro requires a three‐dimensional (3D) culture system presenting mature phenotypes. In this study, we aimed to determine whether aged reaggregate cultures physiologically represent mature brain tissue. Results support that embryo‐derived rat central nervous system (CNS) reaggregate cultures develop into mature‐like tissues, comparable to in vivo maturation, including the following characteristics: (a) progressive reduction in cell proliferation (reduced anti‐Ki‐67 immunoreactivity), (b) progressive restriction of long neurite growth potential (as explant cultures), and (c) increased and sustained synaptic enzyme (acetylcholine esterase, AChE) activity. The acquisition of mature‐like reaggregate cultures has allowed us to pursue the hypothesis that the physiological integrity of 3D CNS cultures may be monitored by synaptic enzyme activity. To assess this hypothesis, mature‐like reaggregates were exposed to H2O2, glutamate, or amyloid β(1–42); each resulted in diminished AChE activity. H2O2 exposure resulted in nuclear fragmentation. Glutamate and amyloid β(1–42) exposure resulted in acetylcholine content reduction. Simultaneous reduction of AChE activity and acetylcholine content verified diminished cholinergic integrity. This scheme exploiting synapse enzyme activity of mature‐like 3D CNS tissue is therefore applicable to age‐related neuropathology research including in vitro screening of conditions potentially affecting synapse integrity, including the promotion of dementia.
- Subjects
CENTRAL nervous system; NUCLEAR fragmentation; INTEGRITY; RATS
- Publication
Biotechnology Progress, 2020, Vol 36, Issue 4, p1
- ISSN
8756-7938
- Publication type
Article
- DOI
10.1002/btpr.2976