Maternal hyperthyroidism in rats impairs stress coping of adult offspring

Abstract

Given the evidence that maternal hyperthyroidism (MH) compromises expression of neuronal cytoskeletal proteins in the late fetal brain by accelerated neuronal differentiation, we investigated possible consequences of MH for the emotional and cognitive functions of adult offspring during acute and subchronic stress coping. Experimental groups consisted of male rat offspring from mothers implanted with osmotic minipumps infusing either thyroxine (MH) or vehicle (Ctrl) during pregnancy. Body weight and T4 level were monitored during the first 3 postnatal months, and no differences were found with the controls. We analyzed hippocampal CA3 pyramidal neurons and dentate granular cell morphology during several postnatal stages and found increased dendritic arborization. On postnatal day 90 a modified subchronic mild stress (SCMS) protocol was applied to experimental subjects for 10 days. The Morris water maze was used before, during, and after application of the SCMS protocol to measure spatial learning. The tail suspension test (TST) and forced-swimming test (FST) were used to evaluate behavioral despair. The MH rats displayed normal locomotor activity and spatial memory prior to SCMS, but impaired spatial learning after acute and chronic stress. In both the FST and TST we found that MH rats spent significantly more time immobile than did controls. Serum corticosterone level was found to increase after 30 min of restraint stress, and corticotropin-releasing factor immunoreactivity was found to be increased in the central nucleus of the amygdala. Our results suggest that MH in rats leads to the offspring being more vulnerable to stress in adulthood.

Accumulation and Endocrine Disrupting Effects of the Flame Retardant Mixture Firemaster® 550 in Rats: An Exploratory Assessment

“…In severe cases, unmanaged hyperthyroidism can induce fetal musculo‐skeletal malformations similar to those reported in the guideline study conducted by Chemtura. Moreover, emerging evidence from animal studies suggests that offspring born to hyperthyroid dams may be more vulnerable to stress , resulting in a more anxious phenotype consistent with what was found in the present study. Thus, maternal hyperthyroidism may contribute to the offspring effects reported here, a possibility that should be followed up in future studies.…”

Thirst Is Associated with Suppression of Habenula Output and Active Stress Coping: Is there a Role for a Non-canonical Vasopressin-Glutamate Pathway?

“…In this test, rats under basal and with 24 h of water deprivation (WD24) were placed into 45 cm height × 30 cm diameter Plexiglas cylinders, filled with water at 25°C, up to a height of 25 cm, and their behavior was recorded over a 6-min test period. The behavior was evaluated offline using the criteria described previously (Detke et al, 1995 ; Zhang et al, 2008 ). Briefly, the observers scored the behaviors as one of the 3 classes, “swimming,” “climbing,” and “immobility,” every 5 s. “Climbing” was scored as movements directed toward the top edge of the cylinder and “immobility” was considered when there was cessation of spatial displacement with or without minor involuntary movements of the hind limbs.…”

Prefrontal–Bed Nucleus Circuit Modulation of a Passive Coping Response Set

“…Tail suspension was used as an expedient assay to assess concurrent changes in stress-evoked behavioral and HPA output while performing optogenetic manipulations. This behavioral assay was developed in mice (Steru et al, 1985), has been adapted for use in rats (Chermat et al, 1986;Izumi et al, 1997;Zhang et al, 2008;Yang et al, 2014;Paumier et al, 2015), and elicits robust stress responses (Strekalova et al, 2004;Stone and Lin, 2008). Rats are suspended by the tail for 10 min so that the hindlimbs were elevated and forelimbs were allowed to touch the floor of the cage (Chermat et al, 1986).…”