Acute stress enhances adult rat hippocampal neurogenesis and activation of newborn neurons via secreted astrocytic FGF2

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Acute stress enhances adult rat hippocampal neurogenesis and activation of newborn neurons via secreted astrocytic FGF2

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DOI: April 16, 2013 Cite as eLife 2013;2:e00362


Stress is a potent modulator of the mammalian brain. The highly conserved stress hormone response influences many brain regions, particularly the hippocampus, a region important for memory function. The effect of acute stress on the unique population of adult neural stem/progenitor cells (NPCs) that resides in the adult hippocampus is unclear. We found that acute stress increased hippocampal cell proliferation and astrocytic fibroblast growth factor 2 (FGF2) expression. The effect of acute stress occurred independent of basolateral amygdala neural input and was mimicked by treating isolated NPCs with conditioned media from corticosterone-treated primary astrocytes. Neutralization of FGF2 revealed that astrocyte-secreted FGF2 mediated stress-hormone-induced NPC proliferation. 2 weeks, but not 2 days, after acute stress, rats also showed enhanced fear extinction memory coincident with enhanced activation of newborn neurons. Our findings suggest a beneficial role for brief stress on the hippocampus and improve understanding of the adaptive capacity of the brain.


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EDK was supported by a CIRM predoctoral fellowship and DoD NDSEG fellowship; LAB was supported by NSF GRFP.

Decision letter

Russ Fernald, Reviewing editor, Stanford University, United States

eLife posts the editorial decision letter and author response on a selection of the published articles (subject to the approval of the authors). An edited version of the letter sent to the authors after peer review is shown, indicating the substantive concerns or comments; minor concerns are not usually shown. Reviewers have the opportunity to discuss the decision before the letter is sent (see review process). Similarly, the author response typically shows only responses to the major concerns raised by the reviewers.

Thank you for choosing to send your work entitled “Acute stress enhances adult hippocampal neurogenesis and memory via secreted astrocytic FGF2 in rats” for consideration at eLife. Your article has been evaluated by a Senior editor and 3 reviewers, one of whom is a member of our Board of Reviewing Editors.

The Reviewing editor and the other reviewers discussed their comments before we reached this decision, and the Reviewing editor has assembled the following comments to help you prepare a revised submission. The reviewers agree that this is a thorough and interesting study, but they have the following suggestions:

1) This study reveals a new domain of the inverse-U phenomenon in stress and glucocorticoid action. To make the paper more broadly appealing, this should be discussed in the Introduction.

2) The Introduction should also include comments about the BLA given its role in mediating interactions between the amygala and hippocampus.

3) To be convinced on the causal role of astrocytic FGF2, additional data are needed to demonstrate that the in vivo increase in FGF2 is from astrocytes. Since neonatal astrocyte cultures are often contaminated, these sources need to be excluded using, e.g., in situ hybridization or immunohistochemistry on hippocampus tissue of similarly aged animals in vivo.

4) A related concern is the certainty that no other members of the FGF family are involved. Is the FGF2 blocking antibody specific to that form?

5) In addition, can you show actual levels of FGF2 present rather than relative levels, and is any FGF2 released from untreated astrocyte cultures (an important question since untreated ACM has no effect on NPC proliferation)?

6) The fear extinction data are interesting, but they feel like they belong in a different paper.


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