Hypoxia Triggers Stem Cell Proliferation Followed by Neuronal Progenitor Cell Differentiation

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Research from the United States has revealed that hypoxia triggers stem cell proliferation, followed by neuronal progenitor cell differentiation. This process may potentially replace lost neurons. The study, published in Brain Research, found that hypoxic stress induces apoptosis of hippocampal CA1 neurons while sparing those in CA2-3. The researchers examined MAP kinase signaling regulation of these dual responses and discovered that JNKs and ERKs were maximally activated by 4 hours, returning approximately to basal levels by 6 hours. Apoptosis of CA1 neurons was maximal by 6-hour hypoxia, although JNK activation had returned to basal levels.

Key Takeaways:

  • Hypoxia triggers stem cell proliferation, which is followed by neuronal progenitor cell differentiation, potentially replacing lost neurons.
  • Hypoxic stress induces apoptosis of hippocampal CA1 neurons while sparing those in CA2-3.
  • JNKs and ERKs are maximally activated by 4 hours, returning approximately to basal levels by 6 hours.
  • Apoptosis of CA1 neurons is maximal by 6-hour hypoxia, although JNK activation has returned to basal levels.
  • JNK-interacting protein 1 (JIP1) and DENN/MADD, which modulate JNK-mediated cell death, are reduced by 6-hour hypoxia.
  • A second peak of ERK1 activation occurs at 24-hour reoxygenation and declines to control levels by 48 hours.
  • Stem cells are detected by antinestin, and cell proliferation is confirmed with anti-PCNA immunohistochemistry and BrdU incorporation.
  • ERKs are implicated in the proliferation response, as BrdU labeling is strikingly reduced with U0126, an inhibitor of ERK activation.

Statistics:

  • 6 hours: Duration of hypoxia exposure
  • 4 hours: Time at which JNKs and ERKs are maximally activated
  • 6 hours: Time at which apoptosis of CA1 neurons is maximal
  • 24 hours: Time at which a second peak of ERK1 activation occurs
  • 48 hours: Time at which ERK1 activation declines to control levels
  • 100%: Reduction of BrdU labeling with U0126 (an inhibitor of ERK activation)

Sources:

  • Li, Z., & Coworker. (2004). Neurogenesis response to hypoxia-induced cell death: map kinase signal transduction mechanisms. Brain Research, 1021(1), 8-19.
  • NewsRx.com & NewsRx.net (2004, November 22). Hypoxia triggers stem cell proliferation followed by neuronal progenitor cell differentiation.
  • Health & Medicine Week editors (2004). Hypoxia triggers stem cell proliferation followed by neuronal progenitor cell differentiation. Health & Medicine Week.