Alteration in 5HT1A Receptor Activity from a Prenatal Exposure to Dexamethasone in a Stressed and Non-Stressed Adult Male Rat

Synthetic glucocorticoids (GC) are used as a clinical therapeutic to stimulate lung development in fetuses that present the risk of preterm delivery. Previous studies have shown that a prenatal exposure to Dexamethasone (DEX) causes a disturbance in normal GC mediation of neuritic outgrowth, cell signaling, and serotonergic systems. Our hypothesis is that a prenatal exposure to DEX during the third trimester of pregnancy alters 5HT1A receptor function. Pregnant dams were injected daily with 150μg/ml/kg of DEX from gestation day 14 through 19. Control dams were treated with and equal volume of saline. Swim stress followed by elevated plus maze testing was conducted on male rats an hour and a half prior to being sacrificed to induce postnatal acute stress. The non-stressed group was also tested and allowed to return to baseline before sacrifice. Hippocampi were analyzed using a radioligand-receptor binding assay and GTPγS35 incorporation (3H-MPPF antagonist and 8-OH-DPAT agonist, respectively). A significant increase in Kd was found in non-stressed DEX-exposed animals compared to non-stressed controls (p

Spatial Learning and Stress Response of Male Rats Prenatally Exposed to Dexamethasone

Dexamethasone is routinely administered to women at risk for a preterm birth in order to enhance fetal lung development and reduce uterine contractions. Research has demonstrated possible behavioral abnormalities in adulthood as a result of dexamethasone treatment. Using nonlinear mixed effects modeling, this study found thatprenatal dexamethasone treatment impaired spatial learning and memory of adult male Sprague-Dawley rats. Prenatal dexamethasone treatment also led to more anxiety related behaviors on Elevated Plus Maze testing 1.5 hours after a stress challenge. Because theassumptions underlying the independent samples t-test were violated, the randomization test was used to compare groups on the Elevated Plus Maze.

A microstructure based model of the deformation mechanisms and flow stress during elevated temperature straining of a magnesium alloy

We show that the variation of flow stress with strain rate and grain size in a magnesium alloy deformed at a constant strain rate and 450 °C can be predicted by a crystal plasticity model that includes grain boundary sliding and diffusion. The model predicts the grain size dependence of the critical strain rate that will cause a transition in deformation mechanism from dislocation creep to grain boundary sliding, and yields estimates for grain boundary fluidity and diffusivity.

The Effects of Altered Prenatal Melatonin Signaling on Adult Behavior and Hippocampal Gene Expression of the Male Rat: A Circadioneuroendocrine-Axis Hypothesis of Psychopathology

Disturbances in melatonin - the neurohormone that signals environmental darkness as part of the circadian circuit of mammals - have been implicated in various psychopathologies in humans. At present, experimental evidence linking prenatal melatonin signaling to adult physiology, behavior, and gene expression is lacking. We hypothesized that administration of melatonin (5 mg/kg) or the melatonin receptor antagonist luzindole (5 mg/kg) to rats in utero would permanently alter the circadian circuit to produce differential growth, adult behavior, and hippocampal gene expressionin the male rat. Prenatal treatment was found to increase growth in melatonin-treated animals. In addition, subjects exposed to melatonin prenatally displayed increased rearing in the open field test and an increased right turn preference in the elevated plusmaze. Rats administered luzindole prenatally, however, displayed greater freezing and grooming behavior in the open field test and improved learning in the Morris water maze. Analysis of relative adult hippocampal gene expression with RT-PCR revealed increasedexpression of brain-derived neurotrophic factor (BDNF) with a trend toward increased expression of melatonin 1A (MEL1A) receptors in melatonin-exposed animals whereas overall prenatal treatment had a significant effect on microtubule-associated protein 2(MAP2) expression. Our data support the conclusion that the manipulation of maternal melatonin levels alters brain development and leads to physiological and behavioral abnormalities in adult offspring. We designate the term circadioneuroendocrine (CNE)axis and propose the CNE-axis hypothesis of psychopathology.