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.
- Abbreviations
- BLA
- basolateral amygdala
- CC
- corpus callosum
- dHPC
- dorsal hippocampus
- EPM
- elevated plus-maze
- LV
- lateral ventricles
- NAc
- nucleus accumbens
- NSF
- novelty-suppressed feeding
- PBS
- phosphate-buffered saline
- PFA
- paraformaldehyde
- PFC
- prefrontal cortex
- RSD
- repeated social defeat
- vHPC
- ventral hippocampus
- ZnT3
- zinc transporter 3
Footnotes
Declarations of interest: none.
Role of the funding source: This research was supported by an NSERC Discovery Grant to RHD and an NHMRC Fellowship and Project Grant to SRS. The funding sources had no involvement in the design or conduct of this research, the writing of this report, or the decision to submit this report for publication.