Maternal separation in rats induces neurobiological and behavioral changes on the maternal side

The time after parturition is a sensitive period for mothers where they are prone to develop psychopathological symptoms. Studies investigating dams after separation from their pups (maternal separation, MS) showed that MS induces alterations similar to postpartum depression. This study aims to give further details on affected behavior and neurobiology of dams after MS. MS in rats from postnatal day 2–20 over four hours daily was performed. Upon reunion, maternal behavior, and ultrasonic vocalization (USV) of dams were measured. On the day of weaning, dams were tested for anxiety-like behavior in the elevated-plus-maze and marble burying test. Then Morc1 mRNA in the medial prefrontal cortex and Nr3c1 encoding the glucocorticoid receptor mRNA in the hippocampus were measured using real-time PCR to examine possible neurobiological correlates in psychopathology and social behavior. GABA and glutamate serum levels were analyzed by high-performance liquid chromatography as peripheral markers for stress-induced psychopathology. MS in dams increased maternal care towards pups even though both groups show high levels of maternal behavior even in late lactation. Furthermore, the emission of 50-kHz and 22-kHz USVs increased significantly. No differences in anxiety-like behavior were detected. MS further reduced Morc1 but not Nr3c1 expression. Serum GABA but not glutamate levels were significantly increased in separated dams. This study reinforces the benefit of investigating dams after MS for studying postpartum stress. Subclinical markers mainly connected to depression, namely Morc1 and GABA, proved to be useful allowing for earlier detection of symptoms of critical postpartum stress.

Severe childhood and adulthood stress associates with neocortical layer-specific reductions of mature spines in psychiatric disorders

Severe stress exposure causes the loss of dendritic spines on cortical pyramidal neurons and induces psychiatric-like symptoms in rodent models. These effects are strongest following early-life stress and are most persistent on apical dendrites. However, the long-term impacts and temporal effects of stress exposure on the human brain remain poorly understood. Using a novel postmortem cohort of psychiatric cases with severe stress experienced in childhood, adulthood, or no severe stress, and matched controls, we aimed to determine the impact of stress timing on pyramidal neuron structure in the human orbitofrontal cortex (OFC). We performed Golgi Cox staining and manually measured the morphology and density of over 22,000 dendritic spines on layer-specific pyramidal neuron apical dendrites. We also quantified glucocorticoid receptor mRNA and protein as a marker of stress dysregulation. Both childhood and adulthood stress were associated with large reductions in mature mushroom spine density (up to 56% loss) in both the superficial (II/III) and deeper layers (V) of the OFC. However, childhood stress caused more substantial reductions to both total and mature mushroom spines. No difference in glucocorticoid receptor mRNA and protein were seen between groups, although both negatively correlated with total spine density within the whole cohort. These findings indicate that severe stress, especially when experienced during childhood, persistently affects the fine morphological properties of neurons in the human OFC. This may impact on cell connectivity in this brain area, and at least partly explain the social and emotional symptoms that originate in the OFC in psychiatric disorders.