Uncoupling protein 2 knockout exacerbates depression-like behaviors in mice via enhancing inflammatory response

After a cold conditioning swim, UCP2-deficient mice are more able to defend against the cold than wild type mice

“…Wild type and UCP2-deficient mice are known to have similar resting concentrations of circulating corticosterone [14, 34], however, we found that UCP2-deficient mice had a higher concentration of circulating corticosterone than wild type mice when measured 24 h after a swim at 26°C (Fig. 5B), coinciding temporally with a greater defense against cold in UCP2-deficient mice than in wild type mice (Fig.…”

“…Because anxiety is a condition that is frequently, but not always comorbid with depression, it is useful to differentiate their mediation from each other. Relevant to a potential role in depression, UCP2-deficient mice exhibit anhedonia and have higher circulating corticosterone after 3 weeks of unpredictable chronic mild stress than wild type mice [13, 14]. To determine the role of UCP2 in a commonly used measure of depressive behavior in rodents, we tested mice in the forced swim test but observed no difference between the duration of immobility of UCP2-deficient and wild type mice and all mice floated longer on day 2 than on day 1.…”

“…In contrast to UCP1 that is found almost exclusively in brown adipose tissue [2], UCP2 is widely distributed throughout the body including the pancreas [3], spleen, kidney [4], immune cells [5], brain [6], and the CNS [7]. This distribution has implicated UCP2 in multiple pathologies including diabetes [8], Parkinson's disease [9], cancer [10, 11], atherosclerosis [12], anxiety [13] and depression [14]. …”

“…UCP2-deficient mice are more anxious than wild type mice in the elevated plus maze [13] in response to defeat stress [13]. UCP2-deficient mice exhibit more anhedonia, measured using the glucose preference test, and have higher concentrations of circulating corticosterone than wild type mice when subjected to chronic mild stress [14]. UCP2-deficient mice have an increased turnover of brain dopamine and serotonin [13], two neurotransmitters involved in depression [15, 16] as well as anxiety [17, 18].…”

“…Yet stressed mice have an increased concentration of UCP2 in the hypothalamus [14], a region of the brain important in thermogenesis and temperature regulation [22]. In many animal models of depression, including chronic mild stress: [5,6]; olfactory bulbectomy: [7]; after high doses of lipopolysaccharides: [8-11]; tail suspension test: [12], depressive-like behavior occurs coincident with changes in body temperature.…”