Neonatal Stress Has a Long-Lasting Sex-Dependent Effect on Anxiety-Like Behavior and Neuronal Morphology in the Prefrontal Cortex and Hippocampus

Abstract

The long-lasting effects of early stress on brain development have been well studied. Recent evidence indicates that males and females respond differently to the same stressor. We examined the chronic effects of daily maternal separation (MS) on behavior and cerebral morphology in both male and female rats. Cognitive and anxiety-like behaviors were evaluated, and neuroplastic changes in 2 subregions of the prefrontal cortex (dorsal agranular insular cortex [AID] and cingulate cortex [Cg3]) and hippocampus (CA1 and dentate gyrus) were measured in adult male and female rats. The animals were subjected to MS on postnatal day (P) 3–14 for 3 h per day. Cognitive and emotional behaviors were assessed in the object/context mismatch task, elevated plus maze, and locomotor activity test in early adulthood (P87–P95). Anatomical assessments were performed in the prefrontal cortex (i.e., cortical thickness and spine density) and hippocampus (i.e., spine density). Sex-dependent effects were observed. MS increased anxiety-related behavior only in males, whereas locomotor activity was higher in females, with no effects on cognition. MS decreased spine density in the AID and increased spine density in the CA1 area in males. Females exhibited an increase in spine density in the Cg3. Our findings confirm previous work that found that MS causes long-term behavioral and anatomical effects, and these effects were dependent on sex and the duration of MS stress.

Chronic postnatal chemogenetic activation of forebrain excitatory neurons evokes persistent changes in mood behavior

“…Adult male mice with a history PNCNO treatment showed both enhanced anxiety- and despair-like behavior, whereas adult female mice exhibited enhanced anxiety-, but not despair-like behavioral changes. Sexually dimorphic effects of early adversity have been previously reported, with females suggested to be resistant to some of the behavioral consequences of early adversity, in particular the programming of despair-like behavioral changes ( Leussis et al, 2012 ; Roman et al, 2004 ; Dimatelis et al, 2016 ; Lundberg et al, 2017 ; Desgent et al, 2012 ; de Melo et al, 2018 ). Our results raise the possibility of sexually dimorphic behavioral consequences of early postnatal chemogenetic activation of forebrain excitatory neurons.…”

Effects of early postnatal exposure to fine particulate matter on emotional and cognitive development and structural synaptic plasticity in immature and mature rats

“…Overall, PM2.5 could impair cognitive and neuropsychiatric development. Sex‐based differences in our model should be further studied, since some behavioral defects were dependent on sex in other disease model (McCarthy, ; de Melo, David Antoniazzi, Hossain, & Kolb, ), although we selected the exposure group randomly to match the quantity and sex ratio of the control group.…”

Long-Lasting Sex-Specific Effects Based On Emotion- and Cognition-Related Behavioral Assessment of Adult Rats After Post-Traumatic Stress Disorder From Different Lengths of Maternal Separation

“…Animals were randomly divided into 8 groups and their behavioral parameters were recorded separately: male control group (M-Control, n = 7), male rats with PTSD (M-PTSD, n = 7), male rats with 3h MS and PTSD (M-MS3h-PTSD, n = 7), male rats with 6h MS and PTSD (M-MS6h-PTSD, n = 7), female control group (F-Control, n = 7), female rats with PTSD (F-PTSD, n = 7), female rats with 3h MS and PTSD (F-MS3h-PTSD, n = 7), and female rats with 6h MS and PTSD (F-MS6h-PTSD, n = 7). In the F/M-MS3h-PTSD groups, litters were separated from their dams for 3h (9:00–12:00) each day (10, 19). In the F/M-MS6h-PTSD groups, litters were separated from their dams for 6h (9:00–15:00) each day (PND 2-PND 14).…”

“…A focus on reliance has been largely ignored in relevant genetic and environmental interaction studies, referring to a dynamic pattern of positive adaptation despite experiencing significant trauma or adversity (17). Early environmental events exert enduring effects on behavioral parameters related to coping with stress, and animal models of stress represent an invaluable tool for investigating the complex relationship between brain development and stress (18, 19). In this study, the MS model was used to mimic early life stress and a potential influencing factor of PTSD.…”