Blunted Behavioral and Molecular Responses to Chronic Mild Stress in Adult Rats with Experience of Infancy Maternal Separation

Abstract

Childhood adversity has profound and persistent effects on brain functions and has been implicated in the etiology of depression. Brain-derived neurotrophic factor (BDNF) and cAMP response element-binding protein (CREB) play critical roles during brain development to maintain neuronal function and structural integrity in adulthood. We therefore investigated the long-term effects of early life adversity on the depression-related behavior and the expression of BDNF and CREB in the hippocampus. Male SpragueDawley newborn rats were subjected to maternal separation for 3 h/day on postnatal days 2-14. After the postnatal day 90, rats with or without the experience of infancy maternal separation received a series of unpredictable chronic mild stress (CMS) for 21 days. Sucrose preference and spontaneous activity in the open field test were recorded, and the expression of BDNF and CREB in the hippocampus was measured by real-time RT-PCR and Western blot analyses. Before exposure to CMS, the rats with maternal separation showed the significant decreases in sucrose preference, spontaneous activity, and hippocampal expression of BDNF and CREB, compared to the animals without maternal separation. In contrast, the rats without maternal separation showed greater decreases of the above indictors after CMS, the levels of which were lower than those observed in the rats with maternal separation. Thus, early life adversity leads to long-term decreases in the capacity of enjoying sweetness, spontaneous activity, and hippocampal expression of BDNF and CREB. Moreover, childhood neglect may decrease the neurobehavioral plasticity, thereby blunting the responses to adulthood stress and increasing the susceptibility to depression.

Anxiety-like behaviour assessments of adolescent rats after repeated maternal separation during early life

“… 27 indicated that after repeated MS (3 h from PND 1 to 14), the Wister adult rats had significantly lower locomotor activity compared with rats presented with decreased MS (15 min from PND 1 to 14). Chang et al 28 reported a similar conclusion to that of the study by Rana. We previously suggested that because individuals express anxiety through behaviour differently, any abnormal behaviour, whether expressed through increased or decreased locomotor activity, signifies increased anxiety 29 .…”

Early Life Stress Activates Glial Cells in the Hippocampus but Attenuates Cytokine Secretion in Response to an Immune Challenge in Rat Pups

“…Microglial cells undergo specific morphological changes in response to acute and chronic stress exposure [59]. Chronic stress induces downregulation of the cAMP response element binding protein (CREB) and of BDNF [60,61]. Thus ELS or MS could sensitize microglial cells to a second challenge, even if this occurs immediately after stress exposure, inducing a different response.…”

The effects of early life stress on reward processing

“…Numerous studies of the effects of maternal separation on sucrose preference have reported decreased preference (Amiri et al, 2016; Bolton et al, 2018; Hui et al, 2011; Sadeghi et al, 2016; Shu et al, 2015) or no change in sucrose preference (Matthews et al, 1996a; Mrdalj et al, 2016; Øines et al, 2012; Rüedi-Bettschen et al, 2005; Shalev and Kafkafi, 2002; Uchida et al, 2010), while others have reported increases in sucrose preference (Ferreira et al, 2013; Vazquez et al, 2005). Table 1 shows the methods employed in these studies.…”