Social defeat stress before pregnancy induces depressive-like behaviours and cognitive deficits in adult male offspring: correlation with neurobiological changes

• Published in: BMC neuroscience Vol. 19; no. 1; p. 61
• Main Authors: Wei, Sheng, Li, Zifa, Ren, Meng, Wang, Jieqiong, Gao, Jie, Guo, Yinghui, Xu, Kaiyong, Li, Fang, Zhu, Dehao, Zhang, Hao, Lv, Rongju, Qiao, Mingqi
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 16.10.2018; BioMed Central; BMC
• Subjects: Adenosine; Adrenocorticotropic hormone; Adult children; Affective disorders; AMP; Analysis; Animal models; Animals; Anxiety; Anxiety - etiology; Anxiety - metabolism; Behavior; Behavioural phenotype; Body weight gain; Brain - metabolism; Brain research; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - metabolism; Cognition Disorders - etiology; Cognition Disorders - metabolism; Cognitive ability; Corticosterone; Cyclic adenosine monophosphate; Cyclic AMP response element-binding protein; Cyclic AMP Response Element-Binding Protein - metabolism; Depression (Mood disorder); Depressive Disorder - etiology; Depressive Disorder - metabolism; Dietary Sucrose; Disease Models, Animal; DNA methylation; Dominance-Subordination; Epidemiology; Experiments; Exploratory Behavior - physiology; Feeding Behavior - physiology; Female; Gene expression; Health aspects; Hippocampus; Hypothalamus; Learning - physiology; Male; Memory; Mental depression; Monoamines; Neurobiochemistry; Neurobiology; Neurotransmitters; Offspring; Pattern recognition; Phosphorylation; Pituitary; Prefrontal cortex; Pregnancy; Prenatal Exposure Delayed Effects; Protein binding; Protein transport; Proteins; Psychiatry; Rats, Wistar; RNA-Binding Proteins - metabolism; Rodents; Serotonin; Serotonin transporter; Social aspects; Social defeat stress; Social interactions; Specific Pathogen-Free Organisms; Stress; Stress before pregnancy; Stress response; Stress, Psychological - metabolism; Sucrose; Surveys; Western blotting; Behavioural phenotype; Social defeat stress; Offspring; Neurobiochemistry; Stress before pregnancy
• ISSN: 1471-2202; 1471-2202
• DOI: 10.1186/s12868-018-0463-7

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. 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. We conclude that SDS before pregnancy might induce depressive-like behaviours, cognitive deficits, and neurobiological alterations in the offspring.