Abstract
T101. Accelerated Maturation Phenotypes in Patient-Derived Cell Models of Bipolar Disorder
Biological psychiatry (1969), Vol.83(9), pp.S167-S168
05/01/2018
DOI: 10.1016/j.biopsych.2018.02.437
Abstract
Background
Bipolar disorder (BP) is a complex neuropsychiatric disorder associated with episodes of altered mood, energy, and sleep. The molecular and cellular mechanisms of BP are poorly understood. Patient-derived induced pluripotent stem cells (iPSC) provide a model for studying neurodevelopment in BP, which may help uncover disease mechanisms.
Methods
We derived iPSC from fibroblasts from neurotypical controls (C) and BP patients, and differentiated them into neurons and astrocytes. We studied neuronal maturation by measuring developmental gene expression as well as electrophysiology. Using fluorescent calcium indicators, we measured spontaneous and activity-evoked calcium transients in BP and C neurons. We also examined ATP-evoked calcium signals in immature and CNTF-matured astrocytes from BP and C subjects.
Results
Immunofluorescence and electrophysiological data suggest that BP neurons matured more quickly and lost progenitor markers at earlier developmental ages than C neurons. BP neurons displayed larger calcium signals in response to chemical stimulation than C neurons. By contrast, in a field depolarization paradigm, BP neurons had smaller calcium signals than C neurons. CNTF maturation altered calcium signaling differentially between BP and C astrocytes.
Conclusions
Our data suggest that cells derived from BP patients may mature more quickly than C cells, and support the hypothesis that BP is a neurodevelopmental disorder. Future studies will seek to identify the signaling pathways involved in maturational differences between BP and C cells, and determine whether maturation in BP cells can be corrected to match C patterns.
Details
- Title: Subtitle
- T101. Accelerated Maturation Phenotypes in Patient-Derived Cell Models of Bipolar Disorder
- Creators
- Aislinn Williams - University of IowaMonica Bame - University of MichiganCynthia DeLong - University of MichiganKatarzyna Glanowska - University of MichiganVictor Cazares - University of MichiganRasika Dhond - University of MichiganAustin Smarsh - University of MichiganCousineau Eric - University of MichiganEmily Martinez - University of MichiganKim-Chew Lim - University of MichiganMelvin McInnis - University of MichiganGeoffrey Murphy - University of MichiganK. Sue O'Shea - University of Michigan
- Resource Type
- Abstract
- Publication Details
- Biological psychiatry (1969), Vol.83(9), pp.S167-S168
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.biopsych.2018.02.437
- ISSN
- 0006-3223
- eISSN
- 1873-2402
- Language
- English
- Date published
- 05/01/2018
- Academic Unit
- Iowa Neuroscience Institute; Psychiatry
- Record Identifier
- 9984066144702771
Metrics
16 Record Views