Rodent models of social stress and neuronal plasticity: Relevance to depressive-like disorders

Abstract

A B S T R A C TExposure to severe or persistent social stress may lead to the development of psychiatric disorders such as anxiety and depression. These mood disorders are associated with structural alterations of neural architecture in limbic brain regions that control emotion, mood and cognition. Structural remodeling may either be a sign of successful adaptation, or of failure to do so. In neuropsychiatric disorders like depression structural remodeling involves apoptosis, reduced neurogenesis, and structural remodeling of neuronal dendrites which most likely reflects the latter. Here we review key findings from animal models of psychosocial stress that have been used to gain insights into the relation between stress-related behavioral disorders like depression and structural plasticity. Specifically, we focus on models having a high face validity like social defeat stress in the resident-intruder paradigm and chronic stress of social subordination in social housing conditions. Moderate to severe social stress appears to stimulate plasticity and neuronal growth in regions of the amygdala, whereas the effects in the hippocampus and prefrontal cortex tend to be opposite. A major focus of the current review is to characterize social stress induced structural changes in these brain regions, aiming to provide insight in pathways and factors that underlie behavioral effects of stress and depression.

Sex-specific and shared expression profiles of vulnerability and resilience to trauma in brain and blood

“…Surprisingly, inspection of overlapping gene module members revealed there were more genes overlapping between the hippocampal and amygdalar modules with opposite directions of effect in females than between the male and female amygdalar modules with same direction of effect, suggesting putative sex and brain region-specific regulation in response to TNFα signaling via NFκΒ. The different direction of effect between amygdala and hippocampus in females parallels previous studies demonstrating stress to increase synaptic plasticity, BDNF levels, and induce dendritic hypertrophy in the amygdala, while having the opposite effect in hippocampus and medial prefrontal cortex [87][88][89][90]. This is also endorsed by the one amygdalar module, detected in females, associated with upregulation in EBR relative to the unexposed CON group; this female EBR module was characterized by upregulation of genes involved in the ECM, stem cell/NPC proliferation, positive regulation of neuron differentiation, and positive regulation of dendritic spine development.…”

Guanosine fast onset antidepressant-like effects in the olfactory bulbectomy mice model

“…The amygdala, involved in the emotional salience of environmental stimuli and modulation of affective states 56 , seems to be key for OBX hyperactivity. Contrasting neurogenesis mechanisms modulate the hippocampus and prefrontal cortex functionality in comparison with the amygdala in rodents submitted to different MDD or stress models 57 . Different modulatory mechanisms are consistent with GUO and Ket effects in SPT and NORT despite the presence of hyperlocomotion.…”

During infant maltreatment, stress targets hippocampus, but stress with mother present targets amygdala and social behavior

“…As with any ecologically relevant naturalistic experimental paradigm using social stimuli, it is impossible to completely separate the social dimension from confounds, such as stimulus complexity (56)(57)(58)(59). It is for this reason that we experimentally deconstructed the pup's complex social experience with the mother and progressively eliminated some of the complexity.…”