Neurogenesis and Helplessness Are Mediated by Controllability in Males But Not in Females
Open accessAbstract
Background Numerous studies have implicated neurogenesis in the hippocampus in animal models of depression, especially those related to controllability and learned helplessness. Here, we tested the hypothesis that uncontrollable but not controllable stress would reduce cell proliferation in the hippocampus of male and female rats and would relate to the expression of helplessness behavior. Methods To manipulate controllability, groups of male and female rats were trained in one session (acute stress) or over seven sessions (repeated stress) to escape a footshock, whereas yoked control subjects could not escape but were exposed to the same amount of stress. Cell proliferation was assessed with immunohistochemistry of bromodeoxyuridine (BrdU) and immunofluorescence of BrdU and neuronal nuclei (NeuN). Separate groups were exposed to either controllable or uncontrollable stress, and their ability to learn to escape during training on a more difficult task was used as a behavioral measure of helplessness. Results Acute stress reduced cell proliferation in males but did not affect proliferation in the female hippocampus. When animals were given the opportunity to learn to control the stress over seven days, males produced more cells than the yoked males without control. Repeated training with controllable stress did not influence proliferation in females. Under all conditions, males were more likely than females to express helplessness behavior, even males that were not previously stressed. Conclusions The modulation of neurogenesis by controllability was evident in males but not in females, as was the expression of helplessness behavior, despite the fact that men are less likely than women to experience depression.
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Acute and chronic stress suppress hippocampal cell proliferation.
“In this study, we demonstrate that acute, and chronic, stress suppress hippocampal cell proliferation, consistent with previous reports (12, 32, 33) and that the antiproliferative effect of stress is blocked by inhibition of IL-1RI.”
From IL-1β is an essential mediator of the antineurogenic and anhedonic effects of stress (2008) · cites this paper as [33]
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BackgroundFailure to escape traumatic shock.
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“Under all conditions, males were more likely than emales to express helplessness behavior, even males that were not previously stressed. onclusions: The modulation of neurogenesis by controllability was evident in males but not in females, as was the expression of elplessness behavior, despite the…”
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- Authors
- Shors, T. J., Mathew, J., Sisti, H. M., Edgecomb, C., Beckoff, S., & Dalla, C.
- Affiliations
- Rutgers, The State University of New Jersey (US)
- Corresponding author
- Shors, Tracey J.
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2007-09
- Volume
- 62
- Issue
- 5
- Pages
- 487-495
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC2692748
- OpenAlex
- W2061012822
- Cited by
- 140
- References
- 7
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 3 · 2022: 1 · 2021: 3 · 2020: 2 · 2019: 9 · 2018: 7 · 2017: 6 · 2016: 8 · 2015: 6 · 2014: 8 · 2013: 11 · 2012: 7
- FWCI
- 4.31
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Public Health Service (NIMH 59970)
- National Institute of Mental Health (R01MH059970)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- hippocampal neurogenesis, learned helplessness, controllability, uncontrollable stress, sex differences, depression, cell proliferation, acute stress, repeated stress, escape training, footshock
- MeSH terms
- Animals, Avoidance Learning, Behavior, Animal, Bromodeoxyuridine, Cell Count, Depression, Disease Models, Animal, Female, Helplessness, Learned, Hippocampus, Male, Neurons, Phosphopyruvate Hydratase, Reaction Time, Sex Characteristics, Stress, Psychological, Rats, Sprague-Dawley, Cell Proliferation, Rats
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