Stress resilience is the ability of neuronal networks to maintain function despite exposure to stress. In this study, we investigated whether stress resilience is an actively developed dynamic process in adult mice. To assess the resilient and anhedonic behavioral phenotypes developed after induction the chronic unpredictable stress, we quantitatively characterized the structural and functional plasticity of excitatory synapses in the hippocampus using a combination of proteomic, electrophysiological, and imaging methods. Our results indicate that stress resilience is a dynamic and multifactorial process manifested by structural, functional, and molecular changes in synapses. We reveal that chronic stress influences palmitoylation, the profiles of which differ between resilient and anhedonic animals. We also observed that stress resilience is associated with structural compensatory plasticity of the postsynaptic parts of synapses.One Sentence SummaryCompensatory remodeling of dendritic spines at the structural and molecular levels underlies stress resilience.
Clinical and preclinical studies show evidence that chronic stress or nutritional deficits in dietary zinc (Zn) intake may be risk factors for developing major depressive disorder (MDD). Furthermore, there may be possible links between low serum Zn levels and development of treatment-resistant depression. In the present work, we combined chronic restraint stress (CRS) and a low-zinc diet (ZnD) in mice and carried out a set of behavioral and biochemical studies. The mice were treated with four different antidepressant compounds, namely, ketamine, Ro 25–6981 (Ro), hyperforin and lanicemine (Hyp + Lan), and imipramine (IMI). We show that CRS or ZnD alone or a combination of CRS and ZnD (CRS + ZnD) induces anhedonia observed in the sucrose preference test (SPT). The behavioral effects of CRS were restored by ketamine or IMI. However, only Hyp + Lan restored the deficits in behavioral phenotype in mice subjected to CRS + ZnD. We also showed that the antidepressant-like effects observed in Hyp + Lan-treated CRS + ZnD mice were associated with changes in the morphology of the dendritic spines (restored physiological level) in the hippocampus (Hp). Finally, we studied the metabolism of ketamine and its brain absorption in CRS and CRS + ZnD mice. Our results suggest that CRS + ZnD does not alter the metabolism of ketamine to (2R,6R;2S,6S)-HNK; however, CRS + ZnD can induce altered bioavailability and distribution of ketamine in the Hp and frontal cortex (FC) in CRS + ZnD animals compared to the control and CRS groups.
Stress resilience is an ability of neuronal networks to maintain their function despite the stress exposure. In this study, we investigate whether stress resilience is an actively developed dynamic process in adult mice. In order to assess the resilient and anhedonic behavioral phenotypes developed after induction the chronic unpredictable stress, we quantitatively characterized the structural and functional plasticity of excitatory synapses in the hippocampus using a combination of proteomic, electrophysiological, and imaging methods. Our results indicate that stress resilience is a dynamic and multifactorial process manifested by structural, functional, and molecular changes in synapses. We reveal that chronic stress influences palmitoylation, whose profiles differ between resilient and anhedonic animals. We also observed that stress resilience is associated with structural compensatory plasticity of the postsynaptic parts of synapses.
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