Strain Differences and Effects of Environmental Manipulation on Astrocytes (Glial Fibrillary Acidic Protein), Glucocorticoid Receptor, and Microglia (Iba1) Immunoreactivity between Wistar-Kyoto and Wistar Females.

BACKGROUND: Depression is often associated with an increase in hypothalamic-pituitary-adrenal (HPA) axis reactivity and immune response. To investigate this relationship, we examined the consequences of environmental manipulation on the neural correlates of the HPA axis and immune response in an animal model of depression, the Wistar-Kyoto (WKY) rat. Additionally, female animals are often overlooked in preclinical research because of the hormone fluctuations inherent in the estrous cycle. METHODS: Female rats were randomly assigned to 1 of 3 environments for 30 days: (1) environmental enrichment (EE), (2) standard housing (SH), and (3) isolated housing (IH). Immunoreactivity of astrocytes (glial fibrillary acidic protein [GFAP]), glucocorticoid receptors (GRs), and microglia (Iba1) in the hippocampus and amygdala were measured using immunohistochemistry. RESULTS: WKY animals had significantly more GR staining area and Iba1 staining intensity and area in the CA1 of the hippocampus. In enriched Wistar rats, GFAP staining intensity and area were greater in the CA1. A trend towards a greater percent of area stained with GR was found in WKY animals as compared to that of the Wistar animals. This was due to WKY females in EE having significantly higher GR staining intensity and area in the amygdala as compared to that of animals in SH. DISCUSSION: These strain differences lend support to the use of WKY animals as an animal model of depression. Furthermore, due to the effects of EE on GFAP and GR staining in WKY females, we suggest that EE can be used as an intervention to potentially alleviate the negative effects of depression.

Corticosterone and immune cytokine characterization following environmental manipulation in female WKY rats.

This study investigated the effects of environmental manipulation on female Wistar Kyoto (WKY), an animal model of depression, and female Wistar rats. It explored the function of the hypothalamic-pituitary-adrenal axis (HPA) and immune system, as they have both been implicated in the pathophysiology of depression. A further goal was to characterize the immune cytokine concentrations of female WKY rats as this has, to our knowledge, never been documented. Animals were assigned to enriched, standard, or impoverished housing for four consecutive weeks. Following this, serum was collected at baseline and post-stress periods to measure the concentration of corticosterone, TNF-α, IL-1ß, and IL-10. WKY animals had significantly higher corticosterone levels at the post-stress time-point than their Wistar counterparts. WKY females in isolation tended to have the lowest corticosterone levels which may indicate that they prefer a solitary environment, a symptom of depression. We observed a significant decrease in TNF-α after enrichment in the Wistar strain. A similar decrease in TNF-α was found in the WKY strain, but there was no difference between environmental conditions. There was a significant increase in pre- to post-stress IL-10 level in both Wistar and WKY animals. WKY females had a significantly lower level of IL-1ß as compared to the Wistar animals at both pre- and post-stress time points. Given this strain difference, it is likely that the WKY rats had a dysregulated HPA axis which further influenced their circulating cytokine levels. Further studies are needed to examine how this pattern of findings plays a role in the pathophysiology of depression.

Environmental manipulation affects depressive-like behaviours in female Wistar-Kyoto rats.

While the efficacy of pharmacological interventions to treat depression has been well-studied in animal models, much less work has been done to shed light on how changes in the immediate environment can impact behaviour. Furthermore, most studies have focused on male rodents despite the prevalence of mood disorders in women. In this study, 36 Wistar Kyoto (validated animal model of depression) and 36 Wistar (control) female rats were used to examine the effects of environmental manipulation on depressive- and anxiety-like behaviours. Animals were assigned to one of three groups: standard (3 rats/cage), enriched (6 rats/cage plus physical enrichment), and isolation (1 rat/cage) housing. The elevated plus maze (EPM) and forced swim test (FST) were conducted prior to, and four weeks after environmental assignment to measure anxiety-like and depressive-like behaviours, respectively. Sucrose preference assessed anhedonia both before and after environmental assignment. Weight was measured every week to monitor weight-gain over time. Post-environment sucrose preference was significantly increased in animals in enriched housing as compared to those in isolated housing in both strains. While there were significant differences between strains in measures of open arm duration in the EPM and immobility in the FST, there appeared to be no differences between environmental groups. The results of this study highlight the importance of environmental factors in the expression of anhedonia. Enrichment appears to reduce anhedonia while isolation increases anhedonia. These effects should be studied further to assess whether longer periods of social and physical enrichment alleviate other symptoms of depression.