Early-life stress affects the structural and functional plasticity of the medial prefrontal cortex in adolescent rats

Abstract

Early life experiences are crucial factors that shape brain development and function due to their ability to induce structural and functional plasticity. Among these experiences, early-life stress (ELS) is known to interfere with brain development and maturation, increasing the risk of future psychopathologies, including depression, anxiety, and personality disorders. Moreover, ELS may contribute to the emergence of these psychopathologies during adolescence. In this present study, we investigated the effects of ELS, in the form of maternal separation (MS), on the structural and functional plasticity of the medial prefrontal cortex (mPFC) and anxiety-like behavior in adolescent male rats. We found that the MS procedure resulted in disturbances in mother-pup interactions that lasted until weaning and were most strongly demonstrated by increases in nursing behavior. Moreover, MS caused atrophy of the basal dendritic tree and reduced spine density on both the apical and basal dendrites in layer II/III pyramidal neurons of the mPFC. The structural changes were accompanied by an impairment of long-term potentiation processes and increased expression of key proteins, specifically glutamate receptor 1, glutamate receptor 2, postsynaptic density protein 95, αCa(2+) /calmodulin-dependent protein kinase II and αCa(2+)/calmodulin-dependent protein kinase II phosphorylated at residue Thr305, that are engaged in long-term potentiation induction and maintenance in the mPFC. We also found that the MS animals were more anxious in the light/dark exploration test. The results of this study indicate that ELS has a significant impact on the structural and functional plasticity of the mPFC in adolescents. ELS-induced adaptive plasticity may underlie the pathomechanisms of some early-onset psychopathologies observed in adolescents.

Gender- and anxiety level-dependent effects of perinatal stress exposure on medial prefrontal cortex

“…The majority of these changes were observed only in male offspring and confined to the apical dendrites of pyramidal neurons in layers II-III (Murmu et al, 2006;Michelsen et al, 2007;Suenaga et al, 2012;Markham et al, 2013;Bock et al, 2014). Comparable changes and retardation of apical dendrites in layers II-III pyramidal neurons were also observed in rats exposed to maternal separation or isolation stress (Silva-Gomez et al, 2003;Bock et al, 2005;Monroy et al, 2010;Chocyk et al, 2013). In the present study, dendritic changes in Sholl analysis were found in both gender; but considering the fact that control males have significantly more complex dendritic branches than females, stress-induced dendritic alterations were more prominent in males.…”

“…While Muhammad and Kolb reported that male and female pups, separated daily for 3 h from the dam during P3-P21, display an increase in the spine density in the mPFC (Muhammad and Kolb, 2011a;Muhammad et al, 2012); SilvaGomez et al reported that 8 weeks of postweaning social isolation causes 48-51% decrease in the spine density of basal dendrites in the mPFC (Silva-Gomez et al, 2003). More recently, Chocyk et al (2013) showed that 3 h maternal separation during P3-P21 causes significant impacts on the structural and functional plasticity in adolescents, having atrophic changes in the basal dendritic tree and reduced spine density on both the apical and basal dendrites in layers II-III pyramidal neurons of the mPFC. Again, controversial results were reported from studies that female and male animals exposed to prenatal stress between E12 and E16 display an increase in the spine density of neurons in the mPFC ; whereas gestational stress between E15 and E20 results in 21% reduction of spine densities in the apical and basal dendrites of neurons in the anterior cingulate cortex (Murmu et al, 2006).…”

Stress during a Critical Postnatal Period Induces Region-Specific Structural Abnormalities and Dysfunction of the Prefrontal Cortex via CRF1

“…Recent studies have reported that early-life stress alters dendritic morphology and spine density of prefrontal pyramidal neurons (Chocyk et al, 2013;Monroy et al, 2010;Muhammad and Kolb, 2011). However, the results are variable.…”

Stress and the social brain: behavioural effects and neurobiological mechanisms

“…Stress at other developmental stages also causes structural alterations. For instance, neonatal stress affected dendritic organization and synaptic plasticity in the PFC in rats [99][100][101] . Post-weaning social isolation specifically reduced the volume of posterodorsal component of the medial amygdala and of the right medial PFC in rats 102,103 .…”