Long Term Sex-Dependent Psychoneuroendocrine Effects of Maternal Deprivation and Juvenile Unpredictable Stress in Rats

Abstract

We have analysed the long-term psychoneuroendocrine effects of maternal deprivation (MD) [24 h at postnatal day (PND) 9] and/or exposure to chronic unpredictable stress (CUS) during the periadolescent period (PND 28 to PND 43) in male and female Wistar rats. Animals were tested in the elevated plus maze (EPM, anxiety) at PND 44 and in two memory tests, spontaneous alternation and novel object recognition (NOT) in adulthood. The expression of hippocampal glucocorticoid (GR) and mineralocorticoid (MR) receptors, as well as of synaptophysin, neural cell adhesion molecule and brain-derived neurotrophic factor, was analysed by in situ hybridisation in selected hippocampal regions. Endocrine determinations of leptin, testosterone and oestradiol plasma levels were carried out by radioimmunoassay. Young CUS animals showed decreased anxiety behaviour in the EPM (increased percentage of time and entries in the open arms) irrespective of neonatal treatment. Memory impairments were induced by the two stressful treatments as was revealed by the NOT, with males being most clearly affected. Although each stressful procedure, when considered separately, induced different (always decrements) effects on the three synaptic molecules analysed and affected males and females differently, the combination of MD and CUS induced an unique disruptive effect on the three synaptic plasticity players. MD induced a long-term significant decrease in hippocampal GR only in males, whereas CUS tended to increase MR in males and decrease MR in females. Both neonatal MD and periadolescent CUS induced marked reductions in testosterone and oestradiol in males, whereas MD male animals also showed significantly decreased leptin levels. By contrast, in females, none of the hormones analysed was altered by any of the stressful procedures. Taking our data together in support of the 'two-hit' hypothesis, MD during neonatal life and/or exposure to CUS during the periadolescent period induced a permanent deficit in memory, which was accompanied by a decrement in markers for hippocampal plasticity. The long-term effects on body weight and hormone levels, particularly among males, might reflect sex-dependent lasting metabolic alterations as well as an impaired reproductive function.

The Val66Met brain-derived neurotrophic factor gene variant interacts with early pain exposure to predict cortisol dysregulation in 7-year-old children born very preterm: Implications for cognition

“…Early life stress can have sex-dependent long-term effects on the responsiveness of the HPA axis (Darnaudery and Maccari, 2008; Viveros et al, 2009; Kaiser and Sachser, 2005), with some studies reporting higher vulnerability or sensitivity in males to the early disturbances compared to females (e.g. (Mueller and Bale, 2008; Llorente et al, 2011), while others report changes in HPA axis function predominantly in females (McCormick et al, 1995; Weinstock, 2007). These differences may be due to different types and timing of the stressors (Bale, 2011).…”

Differential effects of tianeptine on the dorsal hippocampal volume of rats submitted to maternal separation followed by chronic unpredictable stress in adulthood

“…A C C E P T E D When combined, MS at an early age and chronic stress in adulthood may lead to two possible outcomes: either the effects of stress exposure during a lifetime are cumulative and increase the likelihood of developing a disease (Choy et al, 2008;Llorente et al, 2011), or the aversive experiences early in life trigger adaptive processes, thereby rendering an individual better adapted to aversive challenges later in life (Nederhof, 2012;Schmidt, 2010). The first outcome is known as the "cumulative stress" or "two hit" hypothesis, while the second is known as the "mismatch hypothesis" (Nederhof, 2012).…”

Enteric Microbiota–Gut–Brain Axis from the Perspective of Nuclear Receptors

“…The hormonal differences associated with MR correlate with occurrence of cardiovascular diseases in premenopausal woman. Consistently, sex differences exist in the cortisol stress response [598], in response to parental separation of pups [599], in hippocampal MR and GR expression after exposure to stress of adults rats [600,601] and in the prevalence of stress-related psychiatric disorders [602,603]. On the contrary, DEX-treated female rats increase ERβ expression in the hypothalamic PVN and supraoptic nuclei (SON) [604], whereas adrenalectomy reduces ERβ mRNA expression in the PVN, and corticosterone replacement fully reverses this effect in a dose-dependent fashion [605].…”