María I. Sarchi

Long-term effects of prenatal stress on dopamine and glutamate receptors in adult rat brain.

Prenatal stress greatly influences the ability of an individual to manage stressful events in adulthood. Such vulnerability may result from abnormalities in the development and integration of forebrain dopaminergic and glutamatergic projections during the prenatal period. In this study, we assessed the effects of prenatal stress on the expression of selective dopamine and glutamate receptor subtypes in the adult offsprings of rats subjected to repeated restraint stress during the last week of pregnancy. Dopamine D2-like receptors increased in dorsal frontal cortex (DFC), medial prefrontal cortex (MPC), hippocampal CA1 region and core region of nucleus accumbens (NAc) of prenatally stressed rats compared to control subjects. Glutamate NMDA receptors increased in MPC, DFC, hippocampal CA1, medial caudate-putamen, as well as in shell and core regions of NAc. Group III metabotropic glutamate receptors increased in MPC and DFC of prenatally stressed rats, but remained unchanged in all other regions examined. These results indicate that stress suffered during the gestational period has long lasting effects that extend into the adulthood of prenatally stressed offsprings. Changes in dopamine and glutamate receptor subtype levels in different forebrain regions of adult rats suggest that the development and formation of the corticostriatal and corticolimbic pathways may be permanently altered as a result of stress suffered prenatally. Maldevelopment of these pathways may provide a neurobiological substrate for the development of schizophrenia and other idiopathic psychotic disorders.

Early adoption modifies the effects of prenatal stress on dopamine and glutamate receptors in adult rat brain

Stressful stimuli during pregnancy induce complex effects that influence the development of offspring. These effects can be prevented by environmental manipulations during the early postnatal period. Repeated restraint during the last week of pregnancy was used as a model of prenatal stress, and adoption at birth was used to change the postnatal environment. No differences were found in various physical landmarks, except for testis descent, for which all prenatally stressed pups showed a 1‐day delay in comparison with control rats, regardless of the postnatal adoption procedure. Levels of dopamine (DA) D2 and glutamate (Glu) N‐methyl‐D‐aspartate (NMDA) receptors were differentially regulated in different forebrain regions of cross‐fostered adult offspring. Increased concentrations of cortical D2 receptors detected in stressed pups, raised by a gestationally stressed biological mother, were not detected when the pups were raised by a control mother. Control pups raised by a foster mother whether gestationally stressed or not had higher levels of NMDA receptors in cortical areas. These findings suggest that the normal expression of DA and Glu receptors is influenced by in utero experience and by lactation. The complex pattern of receptor changes reflects the high vulnerability of DA and Glu systems to variations both in prenatal and in postnatal environment, particularly for cortical D2 receptors and NMDA receptors in cerebral cortex and nucleus accumbens. In contrast, testis descent appears to be more susceptible to prenatal than to postnatal environmental events.

The molar ratio of retinol-binding protein to transthyretin in the assessment of vitamin A status in adults. Proposal of a cut-off point.

Abstract The molar ratio of retinol-binding protein to transthyretin (RBP:TTR) has been proposed as an indirect method to assess vitamin A status in children with inflammation. Neither reference values nor appropriate cut-off point are available for adults. RBP, TTR and retinol were determined in plasma from 100 healthy adults and 31 low-risk surgical patients with no inflammatory response. RBP:TTR percentile distribution from 99 healthy adults with plasma retinol ≥0.7 μmol/l was: 2.5th = 0.24; 5th = 0.31; 10th = 0.32; 25th = 0.41; 50th = 0.47; 75th = 0.54; 90th = 0.67; 95th = 0.78 and 97.5th = 0.81. In order to define a cut-off point, receiver operating characteristic (ROC) curve was constructed, using plasma retinol as gold standard. ROC curve was based on data from the 131 studied subjects, 11 of whom (8.4%) were classified as deficient on the basis of plasma retinol <0.7 μmol/l. According to ROC curve criteria, RBP:TTR ratio was considered a good test, the area under the curve being 0.822, p<0.001. A cut-off-point of ≤0.37 is proposed to detect vitamin A deficiency in adults, since it allows reaching high sensitivity (81.8%), specificity (79.2%) and predictive value (79.4%). The proposed cut-off point falls between 13th and 14th percentiles.