Elimination of vesicular zinc alters the behavioural and neuroanatomical effects of social defeat stress in mice

Brendan B. McAllister, David K. Wright, Ryan C. Wortman, Sandy R. Shultz, Richard H. Dyck

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)

Abstract

Chronic stress can have deleterious effects on mental health, increasing the risk of developing depression or anxiety. But not all individuals are equally affected by stress; some are susceptible while others are more resilient. Understanding the mechanisms that lead to these differing outcomes has been a focus of considerable research. One unexplored mechanism is vesicular zinc – zinc that is released by neurons as a neuromodulator. We examined how chronic stress, induced by repeated social defeat, affects mice that lack vesicular zinc due to genetic deletion of zinc transporter 3 (ZnT3). These mice, unlike wild type mice, did not become socially avoidant of a novel conspecific, suggesting resilience to stress. However, they showed enhanced sensitivity to the potentiating effect of stress on cued fear memory. Thus, the contribution of vesicular zinc to stress susceptibility is not straightforward. Stress also increased anxiety-like behaviour but produced no deficits in a spatial Y-maze test. We found no evidence that microglial activation or hippocampal neurogenesis accounted for the differences in behavioural outcome. Volumetric analysis revealed that ZnT3 KO mice have larger corpus callosum and parietal cortex volumes, and that corpus callosum volume was decreased by stress in ZnT3 KO, but not wild type, mice.

Original languageEnglish
Pages (from-to)199-213
Number of pages15
JournalNeurobiology of Stress
Volume9
DOIs
Publication statusPublished - 1 Nov 2018

Keywords

  • Chronic stress
  • Depression
  • Fear memory
  • Magnetic resonance imaging (MRI)
  • SLC30A3
  • Synaptic zinc

Cite this

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title = "Elimination of vesicular zinc alters the behavioural and neuroanatomical effects of social defeat stress in mice",
abstract = "Chronic stress can have deleterious effects on mental health, increasing the risk of developing depression or anxiety. But not all individuals are equally affected by stress; some are susceptible while others are more resilient. Understanding the mechanisms that lead to these differing outcomes has been a focus of considerable research. One unexplored mechanism is vesicular zinc – zinc that is released by neurons as a neuromodulator. We examined how chronic stress, induced by repeated social defeat, affects mice that lack vesicular zinc due to genetic deletion of zinc transporter 3 (ZnT3). These mice, unlike wild type mice, did not become socially avoidant of a novel conspecific, suggesting resilience to stress. However, they showed enhanced sensitivity to the potentiating effect of stress on cued fear memory. Thus, the contribution of vesicular zinc to stress susceptibility is not straightforward. Stress also increased anxiety-like behaviour but produced no deficits in a spatial Y-maze test. We found no evidence that microglial activation or hippocampal neurogenesis accounted for the differences in behavioural outcome. Volumetric analysis revealed that ZnT3 KO mice have larger corpus callosum and parietal cortex volumes, and that corpus callosum volume was decreased by stress in ZnT3 KO, but not wild type, mice.",
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Elimination of vesicular zinc alters the behavioural and neuroanatomical effects of social defeat stress in mice. / McAllister, Brendan B.; Wright, David K.; Wortman, Ryan C.; Shultz, Sandy R.; Dyck, Richard H.

In: Neurobiology of Stress, Vol. 9, 01.11.2018, p. 199-213.

Research output: Contribution to journalArticleResearchpeer-review

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