The co-occurrence of zinc deficiency and social isolation has the opposite effects on mood compared with either condition alone due to changes in the central norepinephrine system

Abstract

Nutritional and social environmental problems during the early stages of life are closely associated with the pathophysiology of mood disorders such as depression. Disruption or dysfunction of the central norepinephrine (NE) system is also considered to play a role in mood disorders. Therefore, we evaluated the effects of zinc deficiency and/or social isolation on mood and changes in the central NE system using rats. Compared with the controls, the rats subjected to zinc deficiency or social isolation alone exhibited increased anxiety-related behavior in the elevated plus maze and greater depression-like behavior in the forced swim test. However, the co-occurrence of zinc deficiency and social isolation resulted in decreased anxiety-related behavior and control levels of depression-like behavior. Social isolation alone decreased the rats' cerebral NE concentrations. The expression of the NE transporter was not affected by social isolation alone, but its expression in the locus coeruleus was markedly decreased by the co-occurrence of social isolation and zinc deficiency, and this change was accompanied by an increase in the blood concentration of 3-methoxy-4-hydroxyphenylglycol, which is a marker of central NE system activity. These findings suggest that zinc deficiency or social isolation alone induce anxious or depressive symptoms, but the presence of both conditions has anxiolytic or antidepressive effects. Furthermore, these opposing effects of mood-related behaviors were found to be associated with changes in the central NE system.

Shifts in broadband power and alpha peak frequency observed during long-term isolation

“…Counterintuitively, however, they showed a positive correlation suggesting that higher levels of NA indicate a flatter power spectrum and stronger neural noise. To what extent NA is altered during long-term isolation should be focus of future investigations, but initial evidence suggests that levels of NA are highly reduced during social isolation as investigated in rats 40 .…”

Paradoxical changes in mood-related behaviors on continuous social isolation after weaning

“…Anxiety-related behaviors were evaluated using the EPM as described previously (Mitsuya et al 2015 ; Pellow et al 1985 ). Briefly, the plus-shaped apparatus (situated 65 cm above the floor) consisted of two open arms (45 cm × 10 cm) and two closed arms (45 cm × 10 cm, surrounded by 50 cm high non-transparent walls) that extended from a central platform (10 cm × 10 cm).…”

“…Depressive-like behaviors were evaluated using the FST as described previously (Mitsuya et al 2015 ; Prosolt et al 1977 ). Briefly, the day before the test, each rat was placed into a plastic cylinder (height: 80 cm, diameter: 45 cm) filled with water to a 25-cm depth at 25 ± 1 °C for 15 min on the day after the EPM for the habituation session.…”

The Behavioral Biology of Teams: Multidisciplinary Contributions to Social Dynamics in Isolated, Confined, and Extreme Environments

“…Nutritional deficits can affect the pathophysiology of mood disorders including depression, which can in turn affect individual performance within a team, healthy, and constructive team interactions, and may cause the withdrawal of that individual from team activities. Zinc deficiency is one example of an essential nutrient for maintenance of normal brain function and has been associated with increased depressive-like and anxiety-related behavior (Roohani et al, 2013; Mitsuya et al, 2015). In addition, low vitamin D status and insufficient omega-3 fatty acids are others that are associated with mood disorders because of their link with the production and action of serotonin, a neurochemical that is typically lower in major and bipolar depression, schizophrenia, and other mood disorders (Patrick and Ames, 2015).…”