Brain-region-specific Molecular Responses to Maternal Separation and Social Defeat Stress in Mice

Sachs, Benjamin D.; Tran, Ha Le Bao; Folse, Emily; Caron, Marc G.

doi:10.1016/j.neuroscience.2018.01.018

Cited by 16 publications

(9 citation statements)

References 38 publications

(70 reference statements)

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“…In addition, maternal separation in rats strongly affects the adrenocortical functionality, by regulating GR expression in the dorsal CA1 [66]. In the research on early-life stress in mice, long-term changes in Nr3c1 are Nr3c2 expression are usually not found in either males or females [11,67,68], although there are isolated reports about enhanced hippocampal Nr3c1 expression in adult MS and HD male mice [69] or decreased cortical Nr3c1 expression in adult MS male mice [70]. Therefore, our data support the hypothesis that mice (in contrast to rats) are more resistant to the effects of early-life stress, at least at the level of regulation of the hypothalamic-pituitary-adrenal axis [11,69].…”

Section: Early-life Stress Increases the Expression Of Nr1d1 But Doesmentioning

confidence: 99%

Maternal Separation Early in Life Alters the Expression of Genes Npas4 and Nr1d1 in Adult Female Mice: Correlation with Social Behavior

Ryabushkina

Reshetnikov

Bondar

2020

Behavioural Neurology

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Early-life stress affects neuronal plasticity of the brain regions participating in the implementation of social behavior. Our previous studies have shown that brief and prolonged separation of pups from their mothers leads to enhanced social behavior in adult female mice. The goal of the present study was to characterize the expression of genes (which are engaged in synaptic plasticity) Egr1, Npas4, Arc, and Homer1 in the prefrontal cortex and dorsal hippocampus of adult female mice with a history of early-life stress. In addition, we evaluated the expression of stress-related genes: glucocorticoid and mineralocorticoid receptors (Nr3c1 and Nr3c2) and Nr1d1, which encodes a transcription factor (also known as REVERBα) modulating sociability and anxiety-related behavior. C57Bl/6 mice were exposed to either maternal separation (MS, 3 h once a day) or handling (HD, 15 min once a day) on postnatal days 2 through 14. In adulthood, the behavior of female mice was analyzed by some behavioral tests, and on the day after the testing of social behavior, we measured the gene expression. We found increased Npas4 expression only in the prefrontal cortex and higher Nr1d1 expression in both the prefrontal cortex and dorsal hippocampus of adult female mice with a history of MS. The expression of the studied genes did not change in HD female mice. The expression of stress-related genes Nr3c1 and Nr3c2 was unaltered in both groups. We propose that the upregulation of Npas4 and Nr1d1 in females with a history of early-life stress and the corresponding enhancement of social behavior may be regarded as an adaptation mechanism reversing possible aberrations caused by early-life stress.

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Section: Early-life Stress Increases the Expression Of Nr1d1 But Doesmentioning

confidence: 99%

Maternal Separation Early in Life Alters the Expression of Genes Npas4 and Nr1d1 in Adult Female Mice: Correlation with Social Behavior

Ryabushkina

Reshetnikov

Bondar

2020

Behavioural Neurology

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“…Reverse transcriptions were performed using the Thermo Scientific Maxima First Strand cDNA Synthesis Kit, according to the manufacturer's instructions. Real-time polymerase chain reaction (RT-PCR) was performed as we have described previously (Sachs et al, 2018) using the PowerUp Sybr Green Master Mix rt-PCR kit (Applied Biosystems, Foster City, CA, USA) according to the manufacturer's instructions. Primer sequences were selected from PrimerBank (Wang et al, 2012): GAPDH forward: 5 -CATGTTCCAGTATGACTC CACTC-3 ; GAPDH reverse: 5 -GGCCTCACCCCATTTGAT GT-3 ; complement C4A forward: 5 -GATGACAAGAACGTGA GTGTCC-3 ; complement C4A reverse: 5 -CCCTTTAGCCAC CAATTTCAGG-3 ; IL-1β forward: 5 -TTCAGGCAGGCAGT ATCACTC-3 ; IL-1β reverse: 5 -GAAGGTCCACGGGAAAGA CAC-3 ; IL-6 forward: 5 -TCTATACCACTTCACAAGTCGG A-3 ; IL-6 reverse: 5 -GAATTGCCATTGCACAACTCTTT-3 ; ionized calcium binding adaptor molecule 1 (IBA1) forward: 5 -ATCAACAAGCAATTCCTCGATGA-3 ; IBA1 reverse: 5 -CA GCATTCGCTTCAAGGACATA-3 ; GSK3β forward: 5 -ACAG GCCACAGGAGGTCAGT-3 ; GSK3β reverse: 5 -GATGGCAA CCAGTTCTCCAG-3 .…”

Section: Gene Expression Analysismentioning

confidence: 99%

Brain 5-HT Deficiency Prevents Antidepressant-Like Effects of High-Fat-Diet and Blocks High-Fat-Diet-Induced GSK3β Phosphorylation in the Hippocampus

Karth

Baugher

Daly

et al. 2019

Front. Mol. Neurosci.

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Obesity is associated with an increased risk of depression and anxiety disorders, but the nature of the relationship(s) between obesity and mental illness remains highly controversial. Some argue that depression and anxiety lead to increased consumption of "comfort foods," the intake of which reduces negative affect and promotes obesity. In contrast, others have theorized that negative affect results from chronic excessive consumption of highly palatable foods. The brain serotonin (5-HT) system has long been implicated in both the development and treatment of mental illness. Preclinical studies have shown that low brain 5-HT exacerbates depression-and anxiety-like behaviors induced by stress and blocks reductions in depression-like behavior induced by antidepressants, but the effects of brain 5-HT deficiency on responses to high-fat diet (HFD) have not been explored. The current work used genetically modified mice to evaluate the effects of low 5-HT on behavioral and molecular alterations induced by chronic exposure to HFD. Our results reveal that HFD decreases depression-like behavior and increases some anxiety-like behaviors in wild-type (WT) mice. However, genetic brain 5-HT deficiency blocks HFD-induced reductions in forced swim immobility and prevents HFD-induced increases in hippocampal GSK3β phosphorylation despite having no significant effects on HFD-induced changes in body weight or anxiety-like behavior. Together, our results suggest that brain 5-HT deficiency significantly impacts a subset of behavioral and molecular responses to HFD, a finding that could help explain the complex relationships between obesity and mental illness.

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“…These molecules are located at adherens and/or synaptic junctions, forming inter-neuronal connections and dynamically shaping synaptic plasticity by modulating synapse formation, maturation, and transmission [ 13 – 15 ]. Several CAMs are altered by stress, such as nectin3 [ 16 , 17 ], nectin1 [ 18 , 19 ], neuroligin2 [ 10 , 20 ], β-catenin [ 21 – 23 ], and N-cadherin [ 22 , 24 ]. Evidence also supports mediating roles of CAMs in the effects of stress on behavior and dendritic structure [ 16 , 20 , 25 , 26 ], but the majority of these studies have focused on the hippocampus and postnatal/adult stress [ 16 , 20 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

Prefrontal Nectin3 Reduction Mediates Adolescent Stress-Induced Deficits of Social Memory, Spatial Working Memory, and Dendritic Structure in Mice

Wang

et al. 2020

Neurosci. Bull.

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Chronic stress may disrupt the normal neurodevelopmental trajectory of the adolescent brain (especially the prefrontal cortex) and contribute to the pathophysiology of stress-related mental illnesses, but the underlying molecular mechanisms remain unclear. Here, we investigated how synaptic cell adhesion molecules (e.g., nectin3) are involved in the effects of adolescent chronic stress on mouse medial prefrontal cortex (mPFC). Male C57BL/6N mice were subjected to chronic social instability stress from postnatal days 29 to 77. One week later, the mice exposed to chronic stress exhibited impaired social recognition and spatial working memory, simplified dendritic structure, and reduced spine density in the mPFC. Membrane localization of nectin3 was also altered, and was significantly correlated with behavioral performance. Furthermore, knocking down mPFC nectin3 expression by adeno-associated virus in adolescent mice reproduced the stress-induced changes in behavior and mPFC morphology. These results support the hypothesis that nectin3 is a potential mediator of the effects of adolescent chronic stress on prefrontal structural and functional abnormalities.

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Brain-region-specific Molecular Responses to Maternal Separation and Social Defeat Stress in Mice

Cited by 16 publications

References 38 publications

Maternal Separation Early in Life Alters the Expression of Genes Npas4 and Nr1d1 in Adult Female Mice: Correlation with Social Behavior

Maternal Separation Early in Life Alters the Expression of Genes Npas4 and Nr1d1 in Adult Female Mice: Correlation with Social Behavior

Brain 5-HT Deficiency Prevents Antidepressant-Like Effects of High-Fat-Diet and Blocks High-Fat-Diet-Induced GSK3β Phosphorylation in the Hippocampus

Prefrontal Nectin3 Reduction Mediates Adolescent Stress-Induced Deficits of Social Memory, Spatial Working Memory, and Dendritic Structure in Mice

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