Abstract
Previous studies have reported that maternal chronic stress or depression is linked to an increased risk of affective disorders in progeny. However, the impact of maternal chronic stress before pregnancy on the progeny of animal models is unknown. We investigated the behaviors and the neurobiology of 60-day-old male offspring of female rats subjected to 21 days of resident-intruder stress before pregnancy. An anger stressed parental rat model was established using the resident-intruder paradigm and it was evaluated using behavioral tests. Anger stressed maternal rats showed a significant increase in locomotion and aggression but a reduction in sucrose preference. Offspring subjected to pre-gestational anger stress displayed enhanced aggressive behaviors, reduced anxiety, and sucrose preference. Further, offspring subjected to pre-gestational stress showed significant impairments in the recognition index (RI) on the object recognition test and the number of platform crossings in the Morris water maze test. The monoaminergic system was significantly altered in pre-gestationally stressed offspring, and the expression of phosphorylated cyclic adenosine monophosphate response element binding protein (P-CREB), brain-derived neurotrophic factor (BDNF), and serotonin transporter (SERT) levels in pre-gestational stressed offspring were altered in some brain regions. Fluoxetine was used to treat pre-gestational stressed maternal rats and it significantly reduced the changes caused by stress, as evidenced by both behaviors and neural biochemical indexes in the offspring in some but not all cases. These findings suggest that anger stress before pregnancy could induce aggressive behaviors, cognitive deficits, and neurobiological alterations in offspring.
Highlights
Previous studies have shown that maternal stress has a negative influence on the behaviors of offspring, and it is related to frequently occurring affective diseases among them [1,2,3]
The monoaminergic system was significantly altered in pre-gestationally stressed offspring, and the expression of phosphorylated cyclic adenosine monophosphate response element binding protein (P-CREB), brain-derived neurotrophic factor (BDNF), and serotonin transporter (SERT) levels in pre-gestational stressed offspring were altered in some brain regions
It has recently been reported that the male offspring of dams exposed to chronic unpredictable stress (CUS) before pregnancy are at high risk of developing depressivelike behaviors, and that the abnormal expression of phosphorylated cyclic adenosine monophosphate response element binding protein (P-CREB), brain-derived neurotrophic factor (BDNF), and N-methyl-D-aspartate receptor (NMDA-R) subunits in the hippocampus might play a role in the mechanisms underlying these depressivelike behaviors in CUS offspring [14, 15]
Summary
Previous studies have shown that maternal stress has a negative influence on the behaviors of offspring, and it is related to frequently occurring affective diseases among them [1,2,3]. Epidemiological evidence has indicated that negative spiritual and physiological stresses during pregnancy are risk factors for a series of adverse pregnancy phenomena, including premature delivery and low infant birth weight [4]. These findings were www.impactjournals.com/oncotarget supported by a few other studies [5,6,7]. Researchers have previously used the CUS paradigm [14, 15] to examine the influence of a variety of physical stressors such as electric shock or restraint
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