Social defeat stress before pregnancy induces depressive-like behaviours and cognitive deficits in adult male offspring: correlation with neurobiological changes
Abstract Background Epidemiological surveys and studies with animal models have established a relationship between maternal stress and affective disorders in their offspring. However, whether maternal depression before pregnancy influences behaviour and related neurobiological mechanisms in the offs...
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| Format: | Article |
| Language: | English |
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BMC
2018-10-01
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| Series: | BMC Neuroscience |
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| Online Access: | http://link.springer.com/article/10.1186/s12868-018-0463-7 |
| _version_ | 1811237977350733824 |
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| author | Sheng Wei Zifa Li Meng Ren Jieqiong Wang Jie Gao Yinghui Guo Kaiyong Xu Fang Li Dehao Zhu Hao Zhang Rongju Lv Mingqi Qiao |
| author_facet | Sheng Wei Zifa Li Meng Ren Jieqiong Wang Jie Gao Yinghui Guo Kaiyong Xu Fang Li Dehao Zhu Hao Zhang Rongju Lv Mingqi Qiao |
| author_sort | Sheng Wei |
| collection | DOAJ |
| description | Abstract Background Epidemiological surveys and studies with animal models have established a relationship between maternal stress and affective disorders in their offspring. However, whether maternal depression before pregnancy influences behaviour and related neurobiological mechanisms in the offspring has not been studied. Results A social defeat stress (SDS) maternal rat model was established using the resident-intruder paradigm with female specific pathogen-free Wistar rats and evaluated with behavioural tests. SDS maternal rats showed a significant reduction in sucrose preference and locomotor and exploratory activities after 4 weeks of stress. In the third week of the experiment, a reduction in body weight gain was observed in SDS animals. Sucrose preference, open field, the elevated-plus maze, light–dark box, object recognition, the Morris water maze, and forced swimming tests were performed using the 2-month-old male offspring of the female SDS rats. Offspring subjected to pre-gestational SDS displayed enhanced anxiety-like behaviours, reduced exploratory behaviours, reduced sucrose preference, and atypical despair behaviours. With regard to cognition, the offspring showed significant impairments in the retention phase of the object recognition test, but no effect was observed in the acquisition phase. These animals also showed impairments in recognition memory, as the discrimination index in the Morris water maze test in this group was significantly lower for both 1 h and 24 h memory retention compared to controls. Corticosterone, adrenocorticotropic hormone, and monoamine neurotransmitters levels were determined using enzyme immunoassays or radioimmunoassays in plasma, hypothalamus, left hippocampus, and left prefrontal cortex samples from the offspring of the SDS rats. These markers of hypothalamic–pituitary–adrenal axis responsiveness and the monoaminergic system were significantly altered in pre-gestationally stressed offspring. Brain-derived neurotrophic factor (BDNF), cyclic adenosine monophosphate response element binding protein (CREB), phosphorylated CREB (pCREB), and serotonin transporter (SERT) protein levels were evaluated using western blotting with right hippocampus and right prefrontal cortex samples. Expression levels of BDNF, pCREB, and SERT in the offspring were also altered in the hippocampus and in the prefrontal cortex; however, there was no effect on CREB. Conclusion We conclude that SDS before pregnancy might induce depressive-like behaviours, cognitive deficits, and neurobiological alterations in the offspring. |
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| id | doaj.art-081c3108b5ed4d5380eb678cafce3462 |
| institution | Directory Open Access Journal |
| issn | 1471-2202 |
| language | English |
| last_indexed | 2024-04-12T12:32:40Z |
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| spelling | doaj.art-081c3108b5ed4d5380eb678cafce34622022-12-22T03:32:58ZengBMCBMC Neuroscience1471-22022018-10-0119112210.1186/s12868-018-0463-7Social defeat stress before pregnancy induces depressive-like behaviours and cognitive deficits in adult male offspring: correlation with neurobiological changesSheng Wei0Zifa Li1Meng Ren2Jieqiong Wang3Jie Gao4Yinghui Guo5Kaiyong Xu6Fang Li7Dehao Zhu8Hao Zhang9Rongju Lv10Mingqi Qiao11Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese MedicineLaboratory of Behavioural Brain Analysis, Shandong University of Traditional Chinese MedicineExperimental Center, Shandong University of Traditional Chinese MedicineLaboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese MedicineLaboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese MedicineLaboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese MedicineExperimental Center, Shandong University of Traditional Chinese MedicineLaboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese MedicineLaboratory of Behavioural Brain Analysis, Shandong University of Traditional Chinese MedicineLaboratory of Behavioural Brain Analysis, Shandong University of Traditional Chinese MedicineLaboratory of Behavioural Brain Analysis, Shandong University of Traditional Chinese MedicineLaboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese MedicineAbstract Background Epidemiological surveys and studies with animal models have established a relationship between maternal stress and affective disorders in their offspring. However, whether maternal depression before pregnancy influences behaviour and related neurobiological mechanisms in the offspring has not been studied. Results A social defeat stress (SDS) maternal rat model was established using the resident-intruder paradigm with female specific pathogen-free Wistar rats and evaluated with behavioural tests. SDS maternal rats showed a significant reduction in sucrose preference and locomotor and exploratory activities after 4 weeks of stress. In the third week of the experiment, a reduction in body weight gain was observed in SDS animals. Sucrose preference, open field, the elevated-plus maze, light–dark box, object recognition, the Morris water maze, and forced swimming tests were performed using the 2-month-old male offspring of the female SDS rats. Offspring subjected to pre-gestational SDS displayed enhanced anxiety-like behaviours, reduced exploratory behaviours, reduced sucrose preference, and atypical despair behaviours. With regard to cognition, the offspring showed significant impairments in the retention phase of the object recognition test, but no effect was observed in the acquisition phase. These animals also showed impairments in recognition memory, as the discrimination index in the Morris water maze test in this group was significantly lower for both 1 h and 24 h memory retention compared to controls. Corticosterone, adrenocorticotropic hormone, and monoamine neurotransmitters levels were determined using enzyme immunoassays or radioimmunoassays in plasma, hypothalamus, left hippocampus, and left prefrontal cortex samples from the offspring of the SDS rats. These markers of hypothalamic–pituitary–adrenal axis responsiveness and the monoaminergic system were significantly altered in pre-gestationally stressed offspring. Brain-derived neurotrophic factor (BDNF), cyclic adenosine monophosphate response element binding protein (CREB), phosphorylated CREB (pCREB), and serotonin transporter (SERT) protein levels were evaluated using western blotting with right hippocampus and right prefrontal cortex samples. Expression levels of BDNF, pCREB, and SERT in the offspring were also altered in the hippocampus and in the prefrontal cortex; however, there was no effect on CREB. Conclusion We conclude that SDS before pregnancy might induce depressive-like behaviours, cognitive deficits, and neurobiological alterations in the offspring.http://link.springer.com/article/10.1186/s12868-018-0463-7Social defeat stressStress before pregnancyOffspringBehavioural phenotypeNeurobiochemistry |
| spellingShingle | Sheng Wei Zifa Li Meng Ren Jieqiong Wang Jie Gao Yinghui Guo Kaiyong Xu Fang Li Dehao Zhu Hao Zhang Rongju Lv Mingqi Qiao Social defeat stress before pregnancy induces depressive-like behaviours and cognitive deficits in adult male offspring: correlation with neurobiological changes BMC Neuroscience Social defeat stress Stress before pregnancy Offspring Behavioural phenotype Neurobiochemistry |
| title | Social defeat stress before pregnancy induces depressive-like behaviours and cognitive deficits in adult male offspring: correlation with neurobiological changes |
| title_full | Social defeat stress before pregnancy induces depressive-like behaviours and cognitive deficits in adult male offspring: correlation with neurobiological changes |
| title_fullStr | Social defeat stress before pregnancy induces depressive-like behaviours and cognitive deficits in adult male offspring: correlation with neurobiological changes |
| title_full_unstemmed | Social defeat stress before pregnancy induces depressive-like behaviours and cognitive deficits in adult male offspring: correlation with neurobiological changes |
| title_short | Social defeat stress before pregnancy induces depressive-like behaviours and cognitive deficits in adult male offspring: correlation with neurobiological changes |
| title_sort | social defeat stress before pregnancy induces depressive like behaviours and cognitive deficits in adult male offspring correlation with neurobiological changes |
| topic | Social defeat stress Stress before pregnancy Offspring Behavioural phenotype Neurobiochemistry |
| url | http://link.springer.com/article/10.1186/s12868-018-0463-7 |
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