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Accelerated neuronal and synaptic maturation by BrainPhys medium increases A? secretion and alters A? peptide ratios from iPSC-derived cortical neurons.


ABSTRACT: One of the neuropathological hallmarks of Alzheimer's disease (AD) is cerebral deposition of amyloid plaques composed of amyloid ? (A?) peptides and the cerebrospinal fluid concentrations of those peptides are used as a biomarker for AD. Mature induced pluripotent stem cell (iPSC)-derived cortical neurons secrete A? peptides in ratios comparable to those secreted to cerebrospinal fluid in human, however the protocol to achieve mature neurons is time consuming. In this study, we investigated if differentiation of neuroprogenitor cells (NPCs) in BrainPhys medium, previously reported to enhance synaptic function of neurons in culture, would accelerate neuronal maturation and, thus increase A? secretion as compared to the conventional neural maintenance medium. We found that NPCs cultured in BrainPhys displayed increased expression of markers for cortical deep-layer neurons, increased synaptic maturation and number of astroglial cells. This accelerated neuronal maturation was accompanied by increased APP processing, resulting in increased secretion of A? peptides and an increased A?38 to A?40 and A?42 ratio. However, during long-term culturing in BrainPhys, non-neuronal cells appeared and eventually took over the cultures. Taken together, BrainPhys culturing accelerated neuronal maturation and increased A? secretion from iPSC-derived cortical neurons, but changed the cellular composition of the cultures.

SUBMITTER: Satir TM 

PROVIDER: S-EPMC6969066 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Accelerated neuronal and synaptic maturation by BrainPhys medium increases Aβ secretion and alters Aβ peptide ratios from iPSC-derived cortical neurons.

Satir Tugce Munise TM   Nazir Faisal Hayat FH   Vizlin-Hodzic Dzeneta D   Hardselius Erik E   Blennow Kaj K   Wray Selina S   Zetterberg Henrik H   Agholme Lotta L   Bergström Petra P  

Scientific reports 20200117 1


One of the neuropathological hallmarks of Alzheimer's disease (AD) is cerebral deposition of amyloid plaques composed of amyloid β (Aβ) peptides and the cerebrospinal fluid concentrations of those peptides are used as a biomarker for AD. Mature induced pluripotent stem cell (iPSC)-derived cortical neurons secrete Aβ peptides in ratios comparable to those secreted to cerebrospinal fluid in human, however the protocol to achieve mature neurons is time consuming. In this study, we investigated if d  ...[more]

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