Localized hypoxia within the SGZ determines the early survival of newborn hippocampal granule cells

  1. C Chatzi
  2. E Schnell
  3. G L Westbrook  Is a corresponding author
  1. Vollum Institute, United States
  2. Oregon Health & Science University, United States

Abstract

The majority of adult hippocampal newborn cells die during early differentiation from intermediate progenitors (IPCs) to immature neurons. Neural stem cells in vivo are located in a relative hypoxic environment, and hypoxia enhances their survival, proliferation and stemness in vitro. Thus, we hypothesized that migration of IPCs away from hypoxic zones within the SGZ might result in oxidative damage, thus triggering cell death. Hypoxic niches were observed along the SGZ, composed of adult NSCs and early IPCs, and oxidative byproducts were present in adjacent late IPCs and neuroblasts. Stabilizing hypoxia inducible factor-1α with dimethyloxallyl glycine increased early survival, but not proliferation or differentiation, in neurospheres in vitro and in newly born SGZ cells in vivo. Rescue experiments in Baxfl/fl mutants supported these results. We propose that localized hypoxia within the SGZ contributes to the neurogenic microenvironment and determines the early, activity-independent survival of adult hippocampal newborn cells.

Article and author information

Author details

  1. C Chatzi

    Vollum Institute, Portland, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. E Schnell

    Department of Anesthesiology and Perioperative Medicine, Oregon Health & Science University, Portland, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. G L Westbrook

    Vollum Institute, Portland, United States
    For correspondence
    westbroo@ohsu.edu
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: All procedures were performed according to the National Institutes of Health Guidelines for the Care and Use of Laboratory Animals and have been conducted with the approval of the Institutional Animal Care and Use Committee (#IP00000148) and the Insitutional Biosafety Committee (#04-06) at Oregon Health and Science University.

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Metrics

  • 1,810
    views
  • 339
    downloads
  • 22
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. C Chatzi
  2. E Schnell
  3. G L Westbrook
(2015)
Localized hypoxia within the SGZ determines the early survival of newborn hippocampal granule cells
eLife 4:e08722.
https://doi.org/10.7554/eLife.08722

Share this article

https://doi.org/10.7554/eLife.08722

Further reading

    1. Neuroscience
    2. Stem Cells and Regenerative Medicine
    Alfonso Aguilera, Marta Nieto
    Insight

    A tailored cocktail of genes can reprogram a subset of progenitors to no longer produce glial cells and instead develop into neurons involved in motor control.

    1. Neuroscience
    Merlin Monzel, Pitshaporn Leelaarporn ... Cornelia McCormick
    Research Article

    Aphantasia refers to reduced or absent visual imagery. While most of us can readily recall decade-old personal experiences (autobiographical memories, AM) with vivid mental images, there is a dearth of information about whether the loss of visual imagery in aphantasics affects their AM retrieval. The hippocampus is thought to be a crucial hub in a brain-wide network underlying AM. One important question is whether this network, especially the connectivity of the hippocampus, is altered in aphantasia. In the current study, we tested 14 congenital aphantasics and 16 demographically matched controls in an AM fMRI task to investigate how key brain regions (i.e. hippocampus and visual-perceptual cortices) interact with each other during AM re-experiencing. All participants were interviewed regarding their autobiographical memory to examine their episodic and semantic recall of specific events. Aphantasics reported more difficulties in recalling AM, were less confident about their memories, and described less internal and emotional details than controls. Neurally, aphantasics displayed decreased hippocampal and increased visual-perceptual cortex activation during AM retrieval compared to controls. In addition, controls showed strong negative functional connectivity between the hippocampus and the visual cortex during AM and resting-state functional connectivity between these two brain structures predicted better visualization skills. Our results indicate that visual mental imagery plays an important role in detail-rich vivid AM, and that this type of cognitive function is supported by the functional connection between the hippocampus and the visual-perceptual cortex.