PMID- 30326843 OWN - NLM STAT- MEDLINE DCOM- 20190819 LR - 20231213 IS - 1471-2202 (Electronic) IS - 1471-2202 (Linking) VI - 19 IP - 1 DP - 2018 Oct 16 TI - Social defeat stress before pregnancy induces depressive-like behaviours and cognitive deficits in adult male offspring: correlation with neurobiological changes. PG - 61 LID - 10.1186/s12868-018-0463-7 [doi] LID - 61 AB - 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. FAU - Wei, Sheng AU - Wei S AD - Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, #4655 University Road, University Science Park, Changqing District, Jinan, 250355, China. AD - Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Jinan, 250012, China. AD - Laboratory of Behavioural Brain Analysis, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China. AD - Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China. FAU - Li, Zifa AU - Li Z AD - Laboratory of Behavioural Brain Analysis, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China. AD - Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China. FAU - Ren, Meng AU - Ren M AD - Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China. FAU - Wang, Jieqiong AU - Wang J AD - Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, #4655 University Road, University Science Park, Changqing District, Jinan, 250355, China. FAU - Gao, Jie AU - Gao J AD - Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, #4655 University Road, University Science Park, Changqing District, Jinan, 250355, China. FAU - Guo, Yinghui AU - Guo Y AD - Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, #4655 University Road, University Science Park, Changqing District, Jinan, 250355, China. FAU - Xu, Kaiyong AU - Xu K AD - Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China. FAU - Li, Fang AU - Li F AD - Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, #4655 University Road, University Science Park, Changqing District, Jinan, 250355, China. AD - Fengtai Maternal and Children's Health Hospital of Beijing, Beijing, 100069, China. FAU - Zhu, Dehao AU - Zhu D AD - Laboratory of Behavioural Brain Analysis, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China. FAU - Zhang, Hao AU - Zhang H AD - Laboratory of Behavioural Brain Analysis, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China. FAU - Lv, Rongju AU - Lv R AD - Laboratory of Behavioural Brain Analysis, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China. FAU - Qiao, Mingqi AU - Qiao M AUID- ORCID: 0000-0001-7310-1206 AD - Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, #4655 University Road, University Science Park, Changqing District, Jinan, 250355, China. qmingqi@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181016 PL - England TA - BMC Neurosci JT - BMC neuroscience JID - 100966986 RN - 0 (Bdnf protein, rat) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Creb1 protein, rat) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (Dietary Sucrose) RN - 0 (RNA-Binding Proteins) RN - 0 (Sert1 protein, rat) MH - Animals MH - Anxiety/etiology/metabolism MH - Brain/*metabolism MH - Brain-Derived Neurotrophic Factor/metabolism MH - Cognition Disorders/etiology/*metabolism MH - Cyclic AMP Response Element-Binding Protein/metabolism MH - Depressive Disorder/etiology/*metabolism MH - Dietary Sucrose MH - Disease Models, Animal MH - Dominance-Subordination MH - Exploratory Behavior/physiology MH - Feeding Behavior/physiology MH - Female MH - Learning/physiology MH - Male MH - Phosphorylation MH - Pregnancy MH - *Prenatal Exposure Delayed Effects MH - RNA-Binding Proteins/metabolism MH - Rats, Wistar MH - Specific Pathogen-Free Organisms MH - *Stress, Psychological/metabolism PMC - PMC6192280 OTO - NOTNLM OT - *Behavioural phenotype OT - *Neurobiochemistry OT - *Offspring OT - *Social defeat stress OT - *Stress before pregnancy EDAT- 2018/10/18 06:00 MHDA- 2019/08/20 06:00 PMCR- 2018/10/16 CRDT- 2018/10/18 06:00 PHST- 2017/09/04 00:00 [received] PHST- 2018/10/08 00:00 [accepted] PHST- 2018/10/18 06:00 [entrez] PHST- 2018/10/18 06:00 [pubmed] PHST- 2019/08/20 06:00 [medline] PHST- 2018/10/16 00:00 [pmc-release] AID - 10.1186/s12868-018-0463-7 [pii] AID - 463 [pii] AID - 10.1186/s12868-018-0463-7 [doi] PST - epublish SO - BMC Neurosci. 2018 Oct 16;19(1):61. doi: 10.1186/s12868-018-0463-7.