What Do the Animal Studies of Stress Resilience Teach Us?

Abstract

Long-lasting stress factors, both biological and psychological, are commonly accepted as the main cause of depressive disorders. Several animal models, using various stressful stimuli, have been used to find biochemical and molecular alterations that could help us understand the etiopathogenesis of depression. However, recent sophisticated studies indicate that the most frequently used animal models of stress only capture a portion of the molecular features associated with complex human disorders. On the other hand, some of these models generate groups of animals resilient to stress. Studies of the mechanisms of stress resilience bring us closer to understanding the process of adapting to aversive stimuli and the differences between stress-susceptible vs. resilient phenotypes. Especially interesting in this context is the chronic mild stress (CMS) experimental paradigm, most often using rats. Studies using this animal model have revealed that biochemical (e.g., the dopamine D2 receptor) and molecular (e.g., microRNA) alterations are dynamic (i.e., depend on stress duration, 2 vs. 7 weeks) and much more pronounced in stress-resilient than stress-susceptible groups of animals. We strongly suggest that studies aimed at understanding the molecular and biochemical mechanisms of depression must consider these dynamics. A good candidate to serve as a biomarker in such studies might be serum microRNA, since it can be obtained relatively easily from living individuals at various time points.

Spontaneous Activity of CB2 Receptors Attenuates Stress-Induced Behavioral and Neuroplastic Deficits in Male Mice

“…This apparent discrepancy was observed in a recent study published by our group (Fernandes et al, 2021). In addition, chronic unpredictable stress can be used to determine sub-populations of mice that respond different to stress (resilient versus susceptible) and specific molecular markers that could be used as future tools to understand how stress influence behaviors and, translationally, psychiatric disorders (Torrisi et al, 2021;Dziedzicka-Wasylewska et al, 2021). The participation of CB2 receptors in resilience events remain to be elucidated.…”

The miRNome of Depression

“…Recent studies suggest that stress-related mood disorders are an effect of complex genetic, epigenetic and environmental interactions [ 12 , 13 , 14 , 15 ]. Stress responses are more associated with multiple small and often dynamic molecular changes in homeostatic balance, rather than with one genetic factor of strong phenotypic penetration [ 16 , 17 , 18 , 19 ]. As depression is a multifaceted phenotype, it is important to study the biochemical pathways that can regulate overall allostasis of the brain.…”

Synergic action of L-acetylcarnitine and L-methylfolate in Mouse Models of Stress-Related Disorders and Human iPSC-Derived Dopaminergic Neurons

“…This novel form of intervention is predicted to be effective in the management of patients with TRD, in which non-monoaminergic drugs have better chances of success. Our findings lay the groundwork for an in-depth analysis of the synergism between LAC and MF in additional preclinical models, such as 1) models that are able to identify groups of animals resilient to both acute ( Torrisi et al, 2020 ) and chronic ( Dziedzicka-Wasylewska et al, 2021 ) stress; 2) models in which LAC and MF are combined with subthreshold doses of conventional antidepressants (e.g., SSRIs or SNRIs); and, 3) experimental animal models of TRD, characterized by a reduced or absent response to antidepressants ( Planchez et al, 2019 ; Kelly et al, 2022 ).…”