title: Brain Aggregates: An Effective In Vitro Cell Culture System Modeling Neurodegenerative Diseases.
abstract: Drug discovery for neurodegenerative diseases is particularly challenging because of the discrepancies in drug effects between in vitro and in vivo studies. These discrepancies occur in part because current cell culture systems used for drug screening have many limitations. First, few cell culture systems accurately model human aging or neurodegenerative diseases. Second, drug efficacy may differ between dividing and stationary cells, the latter resembling nondividing neurons in the CNS. Brain aggregates (BrnAggs) derived from embryonic day 15 gestation mouse embryos may represent neuropathogenic processes in prion disease and reflect in vivo drug efficacy. Here, we report a new method for the production of BrnAggs suitable for drug screening and suggest that BrnAggs can model additional neurological diseases such as tauopathies. We also report a functional assay with BrnAggs by measuring electrophysiological activities. Our data suggest that BrnAggs could serve as an effective in vitro cell culture system for drug discovery for neurodegenerative diseases.
authors: From the Department of Pathology (MA, AO, SJD) and Institute for Neurodegenerative Diseases (MA, SJD), University of California San Francisco, California; Department of Pharmacology, University of Washington, Seattle, Washington (FK); and McLaughlin Research Institute, Great Falls, Montana (RP, GC). mahn@ind.ucsf.edu.
authors: Misol
authors: M
authors: Ahn
authors: From the Department of Pathology (MA, AO, SJD) and Institute for Neurodegenerative Diseases (MA, SJD), University of California San Francisco, California; Department of Pharmacology, University of Washington, Seattle, Washington (FK); and McLaughlin Research Institute, Great Falls, Montana (RP, GC).
authors: Franck
authors: F
authors: Kalume
authors: From the Department of Pathology (MA, AO, SJD) and Institute for Neurodegenerative Diseases (MA, SJD), University of California San Francisco, California; Department of Pharmacology, University of Washington, Seattle, Washington (FK); and McLaughlin Research Institute, Great Falls, Montana (RP, GC).
authors: Rose
authors: R
authors: Pitstick
authors: From the Department of Pathology (MA, AO, SJD) and Institute for Neurodegenerative Diseases (MA, SJD), University of California San Francisco, California; Department of Pharmacology, University of Washington, Seattle, Washington (FK); and McLaughlin Research Institute, Great Falls, Montana (RP, GC).
authors: Abby
authors: A
authors: Oehler
authors: From the Department of Pathology (MA, AO, SJD) and Institute for Neurodegenerative Diseases (MA, SJD), University of California San Francisco, California; Department of Pharmacology, University of Washington, Seattle, Washington (FK); and McLaughlin Research Institute, Great Falls, Montana (RP, GC).
authors: George
authors: G
authors: Carlson
authors: From the Department of Pathology (MA, AO, SJD) and Institute for Neurodegenerative Diseases (MA, SJD), University of California San Francisco, California; Department of Pharmacology, University of Washington, Seattle, Washington (FK); and McLaughlin Research Institute, Great Falls, Montana (RP, GC).
authors: Stephen J
authors: SJ
authors: DeArmond
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000367:Age Factors; D000818:Animals; D001921:Brain / Q000166:cytology*; D018929:Cell Culture Techniques / Q000379:methods*; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology*; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D009457:Neuroglia / Q000502:physiology; D009474:Neurons / Q000502:physiology; D011247:Pregnancy; D026941:Sodium Channel Blockers / Q000494:pharmacology; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D026941:Sodium Channel Blockers; D016875:tau Proteins
keywords: Brain aggregates; Dendritic degeneration; Drug screening; Neurodegeneration; Tau.