Strain Differences in the Chronic Mild Stress Animal Model of Depression and Anxiety in Mice

Jung, Younghun; Hong, Sa-Ik; Ma, Shi-Xun; Hwang, Ji-Young; Kim, Jun-Sup; Lee, Ju‐Hyun; Seo, Jee-Yeon; Lee, Seok‐Yong; Jang, Choon‐Gon

doi:10.4062/biomolther.2014.058

Cited by 49 publications

(28 citation statements)

References 36 publications

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“…We observed increased exploratory activity specifically in DBA in four independent tests: in the first light phase of the 24h activity test, in the open field, elevated plus maze as well as in the SPSN test, while BL6 showed hyperactivity in elevated plus maze and a trend in the open field and 24h activity. Similar increases in center time and open arm visits have been reported before [ 46 , 69 ], but other studies reported reductions [ 70 – 73 ]. We attribute these contradictory results as being caused by differences in housing condition, testing history and strain background, factors that have all been shown to influence exploration in open field and elevated plus maze [ 74 ].…”

Section: Discussionsupporting

confidence: 83%

Unpredictable chronic mild stress differentially impairs social and contextual discrimination learning in two inbred mouse strains

et al. 2017

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Alterations in the social and cognitive domain are considered important indicators for increased disability in many stress-related disorders. Similar impairments have been observed in rodents chronically exposed to stress, mimicking potential endophenotypes of stress-related psychopathologies such as major depression disorder (MDD), anxiety, conduct disorder, and posttraumatic stress disorder (PTSD). Data from numerous studies suggest that deficient plasticity mechanisms in hippocampus (HC) and prefrontal cortex (PFC) might underlie these social and cognitive deficits. Specifically, stress-induced deficiencies in neural plasticity have been associated with a hypodopaminergic state and reduced neural plasticity persistence. Here we assessed the effects of unpredictable chronic mild stress (UCMS) on exploratory, social and cognitive behavior of females of two inbred mouse strains (C57BL/6J and DBA/2J) that differ in their dopaminergic profile. Exposure to chronic stress resulted in impaired circadian rhythmicity, sociability and social cognition in both inbred strains, but differentially affected activity patterns and contextual discrimination performance. These stress-induced behavioral impairments were accompanied by reduced expression levels of brain derived neurotrophic factor (BDNF) in the prefrontal cortex. The strain-specific cognitive impairment was coexistent with enhanced plasma corticosterone levels and reduced expression of genes related to dopamine signaling in hippocampus. These results underline the importance of assessing different strains with multiple test batteries to elucidate the neural and genetic basis of social and cognitive impairments related to chronic stress.

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Section: Discussionsupporting

confidence: 83%

Unpredictable chronic mild stress differentially impairs social and contextual discrimination learning in two inbred mouse strains

et al. 2017

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“…Firstly, the rats we used are outbred. Since genetic differences may contribute to the behavioral effects of rodents in models of depression [ 58 ], it would be more ideal to use inbred strains in the future. Secondly, we were unable to have a pre- and post-stress brain comparison due to laboratory regulations limiting the physical movement of the animals after r-fMRI.…”

Section: Discussionmentioning

confidence: 99%

Effects of stress on behavior and resting-state fMRI in rats and evaluation of Telmisartan therapy in a stress-induced depression model

Yang

Xia

et al. 2018

BMC Psychiatry

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BackgroundThe etiology of depression and its effective therapeutic treatment have not been clearly identified. Using behavioral phenotyping and resting-state functional magnetic resonance imaging (r-fMRI), we investigated the behavioral impact and cerebral alterations of chronic unpredictable mild stress (CUMS) in the rat. We also evaluated the efficacy of telmisartan therapy in this rodent model of depression.MethodsThirty-two rats were divided into 4 groups: a control group(C group), a stress group(S group), a stress + telmisartan(0.5 mg/kg)group (T-0.5 mg/kg group) and a stress + telmisartan(1 mg/kg) group (T-1 mg/kg group). A behavioral battery, including an open field test (OFT), a sucrose preference test (SPT), and an object recognition test (ORT), as well as r-fMRI were conducted after 4 weeks of CUMS and telmisartan therapy. The r-fMRI data were analyzed using the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) approach. The group differences in the behavior and r-fMRI test results as well as the correlations between these 2 approaches were examined.ResultsCUMS reduced the number of rearings and the total moved distance in OFT, the sucrose preference in SPT, and novel object recognition ability in ORT. The telmisartan treatment (1 mg/kg) significantly improved B-A/B + A in the ORT and improved latency scores in the OFT and SPT. The S group exhibited a decreased ReHo in the motor cortex and pons, but increased ReHo in the thalamus, visual cortex, midbrain, cerebellum, hippocampus, hypothalamus, and olfactory cortex compared to the C group. Telmisartan (1 mg/kg)reversed or attenuated the stress-induced changes in the motor cortex, midbrain, thalamus, hippocampus, hypothalamus, visual cortex, and olfactory cortex. A negative correlation was found between OFT rearing and ReHo values in the thalamus. Two positive correlations were found between ORT B-A and the ReHo values in the olfactory cortexand pons.ConclusionsTelmisartan may be an effective complementary drug for individuals with depression who also exhibit memory impairments. Stress induced widespread regional alterations in the cerebrum in ReHo measures while telmissartan can reverse part of theses alterations. These data lend support for future research on the pathology of depression and provide a new insight into the effects of telmisartan on brain function in depression.

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“…The novelty-suppressed feeding test (NSF) was adapted from previous studies 40 , 41 . The mice were deprived of food for 24 h before the test in their home cages.…”

Section: Methodsmentioning

confidence: 99%

Molecular hydrogen increases resilience to stress in mice

Gao

Song

Wang

et al. 2017

Sci Rep

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The inability to successfully adapt to stress produces pathological changes that can lead to depression. Molecular hydrogen has anti-oxidative and anti-inflammatory activities and neuroprotective effects. However, the potential role of molecular hydrogen in stress-related disorders is still poorly understood. The present study aims to investigate the effects of hydrogen gas on resilience to stress in mice. The results showed that repeated inhalation of hydrogen-oxygen mixed gas [67%:33% (V/V)] significantly decreased both the acute and chronic stress-induced depressive- and anxiety-like behaviors of mice, assessed by tail suspension test (TST), forced swimming test (FST), novelty suppressed feeding (NSF) test, and open field test (OFT). ELISA analyses showed that inhalation of hydrogen-oxygen mixed gas blocked CMS-induced increase in the serum levels of corticosterone, adrenocorticotropic hormone, interleukin-6, and tumor necrosis factor-α in mice exposed to chronic mild stress. Finally, inhalation of hydrogen gas in adolescence significantly increased the resilience to acute stress in early adulthood, which illustrates the long-lasting effects of hydrogen on stress resilience in mice. This was likely mediated by inhibiting the hypothalamic-pituitary-adrenal axis and inflammatory responses to stress. These results warrant further exploration for developing molecular hydrogen as a novel strategy to prevent the occurrence of stress-related disorders.

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Strain Differences in the Chronic Mild Stress Animal Model of Depression and Anxiety in Mice

Cited by 49 publications

References 36 publications

Unpredictable chronic mild stress differentially impairs social and contextual discrimination learning in two inbred mouse strains

Unpredictable chronic mild stress differentially impairs social and contextual discrimination learning in two inbred mouse strains

Effects of stress on behavior and resting-state fMRI in rats and evaluation of Telmisartan therapy in a stress-induced depression model

Molecular hydrogen increases resilience to stress in mice

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