Abstract
Social isolation is considered a stressful situation that results in increased physiological reactivity to novel stimuli, altered behaviour, and impaired brain function. Here, we investigated the effects of long-term social isolation on working memory, spatial learning/memory, hippocampal synaptic transmission, and synaptic proteins in the brain of adult female and male Octodon degus. The strong similarity between degus and humans in social, metabolic, biochemical, and cognitive aspects, makes it a unique animal model that can be highly applicable for further social, emotional, cognitive, and aging studies. These animals were socially isolated from post-natal and post-weaning until adulthood. We also evaluated if re-socialization would be able to compensate for reactive stress responses in chronically stressed animals. We showed that long-term social isolation impaired the HPA axis negative feedback loop, which can be related to cognitive deficits observed in chronically stressed animals. Notably, re-socialization restored it. In addition, we measured physiological aspects of synaptic transmission, where chronically stressed males showed more efficient transmission but deficient plasticity, as the reverse was true on females. Finally, we analysed synaptic and canonical Wnt signalling proteins in the hypothalamus, hippocampus, and prefrontal cortex, finding both sex- and brain structure-dependent modulation, including transient and permanent changes dependent on stress treatment.
Highlights
Social isolation is considered a stressful situation that results in increased physiological reactivity to novel stimuli, altered behaviour, and impaired brain function
The siblings remained together until postnatal day (PND) 90, and thereafter they were raised as sex-matched groups of three siblings from PND 91 until the end of the experiment when degus reached 25-months old (Partial isolation group, protein during early stress (PI), Fig. 1b). (ii-b) From PND 36 until the end of the experiment, male and female degus were individually housed in standard rodent cages, where they had olfactory, acoustic, partial visual, but not physical contact with conspecifics (Chronic isolation group, CI, Fig. 1c)
For the total β-catenin levels in the hypothalamus of female degus, we found a statistically significant effect of stress treatment [F(3,8) = 21.88, p < 0.01], where β-catenin was higher in PI and CI compared to CTL (Fig. 6e)
Summary
Social isolation is considered a stressful situation that results in increased physiological reactivity to novel stimuli, altered behaviour, and impaired brain function. The strong similarity between degus and humans in social, metabolic, biochemical, and cognitive aspects, makes it a unique animal model that can be highly applicable for further social, emotional, cognitive, and aging studies These animals were socially isolated from post-natal and post-weaning until adulthood. We showed that long-term social isolation impaired the HPA axis negative feedback loop, which can be related to cognitive deficits observed in chronically stressed animals. Under repetitive stress, the body will generate a GC response that anticipates the stress episode, having different impacts during juvenile and adult stages[14,15,16] In this way, the biological effects of GCs are usually adaptive, becoming essential in the regulation of metabolic, cardiovascular, and immune systems, and in the modulation of learning strategies and memory processes[16,17,18]. Depending on the circumstances, GCs affect cognitive performance in a context-specific manner that can be either adaptive or pathological[16]
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