Beta-adrenoceptor pathway enhances mitochondrial function in human neural stem cells via rotary cell culture system

Ming Chang Chiang, Heng Lin, Yi Chuan Cheng, Chia Hui Yen, Rong Nan Huang, Kuan Hung Lin

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The structure and function of the human nervous system are altered in space when compared with their state on earth. To investigate directly the influence of simulated microgravity conditions which may be beneficial for cultivation and proliferation of human neural stem cells (hNSCs), the rotary cell culture system (RCCS) developed at the National Aeronautics and Space Administration (NASA) was used. RCCS allows the creation of a unique microgravity environment of low shear force, high-mass transfer and enables three-dimensional (3D) cell culture of dissimilar cell types. The results show that simulated microgravity using an RCCS would induce β-adrenoceptor, upregulate cAMP formation and activate both PKA and CREB (cAMP response element binding protein) pathways. The expression of intracellular mitochondrial genes, including PGC1α (PPAR coactivator 1α), nuclear respiratory factors 1 and 2 (NRF1 and NRF2) and mitochondrial transcription factor A (Tfam), regulated by CREB, were all significantly increased at 72. h after the onset of microgravity. Accordingly and importantly, the ATP level and amount of mitochondrial mass were also increased. These results suggest that exposure to simulated microgravity using an RCCS would induce cellular proliferation in hNSCs via an increased mitochondrial function. In addition, the RCCS bioreactor would support hNSCs growth, which may have the potential for cell replacement therapy in neurological disorders.

Original languageEnglish
Pages (from-to)130-136
Number of pages7
JournalJournal of Neuroscience Methods
Volume207
Issue number2
DOIs
Publication statusPublished - Jun 15 2012

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Keywords

  • Human neural stem cells
  • Mitochondrial function
  • PGC1α
  • Rotary cell culture system

ASJC Scopus subject areas

  • Neuroscience(all)

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