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M Vallée

Publications and source records attributed to M Vallée.

At least 37 records · Page 2Linked to original sources

Early and later adoptions have different long-term effects on male rat offspring.

Both prenatal and postnatal environmental factors exert complex influences on the development of an organism. Previous studies have demonstrated that intervening events during the prenatal period can have different and even opposite effects than similar intervening events occurring in the postnatal period. We have reported previously that early postnatal adoption prevents prenatal stress-induced long-term impairments in glucocorticoid feedback. To characterize further the effects of adoptions during the postnatal period, adoptions have been performed at different times, and the effect on the postnatal ontogeny of the hypothalamo-pituitary-adrenal axis has been investigated. Adoptions were performed during the first hour after birth (A1) and on the fifth (A5) and twelfth (A12) days after birth. At each of these times, other litters (S1, S5, S12) underwent a "separation" controlling for the 1 min maternal separation necessary for the adoptions. Locomotor behavior, cognition, and stress-induced corticosterone secretion in the adult male offspring have been examined, along with maternal behavior. Early adoption (A1) was found to prevent the prolonged stress-induced secretion of corticosterone evident in early separated (S1) offspring. Similarly, A1 rats demonstrated lower novelty-induced locomotion and improved recognition performance in a Y-maze compared to S1 offspring. However, later adoption (A5, A12) prolonged stress-induced corticosterone secretion, increased the locomotor response to novelty, and disrupted cognitive performance in the offspring. Only the early adoption increased maternal licking behavior, a factor that may have a protective effect on the pups. Taken together, these results suggest that the same postnatal manipulation realized at different times can induce different, or even opposite, effects on the behavioral and neuroendocrine characteristics of the adult offspring.

Aging↗

Long-term effects of prenatal stress and handling on metabolic parameters: relationship to corticosterone secretion response.

The prenatal and postnatal environment exerts a long-term influence on the stress-response of the hypothalamic-pituitary-adrenal (HPA) axis. In this study, the long-term effects of prenatal and postnatal manipulations and their related changes on glucocorticoid secretion were examined on metabolic parameters in adult rats. Plasma glucose levels, body weight and basal feeding behavior were measured. We show that modifications of the prenatal and postnatal environment have opposite long-term effects on these parameters, except for blood glucose, which was increased in prenatally stressed animals. Although the mechanisms underlying these phenomena remain to be elucidated, the observations show that perinatal manipulations have long-term effects on metabolic functions related to HPA activity.

Animals↗

Behavioral reactivity to novelty during youth as a predictive factor of stress-induced corticosterone secretion in the elderly--a life-span study in rats.

Inter- and intra-individual differences in hypothalamo-pituitary adrenal (HPA) axis activity and behavioral reactivity to novelty between young and old rats were evidenced in this longitudinal life-span study. Higher responders to novelty (HR) had a higher corticosterone secretion which showed a quicker increase with age than did the others (LR); the differences in response to novelty observed in youth were no longer apparent in the old rats. Response to novelty in youth is a predictive factor of accelerated aging of the HPA axis. These early changes, which precede the appearance of the memory deficits, may be a causal factor. Disappearance of behavioral and endocrinological inter-individual differences at 21 months highlights the importance of not restricting aging studies to old subjects.

Aging↗

Regulation of guinea pig adrenal P450c21 messenger RNA, protein and activity by RU486.

The role of ACTH, forskolin and 8Br-cAMP on the regulation of mRNA abundance, protein levels and enzymatic activity of cytochrome P450 21-hydroxylase (P450c21, CYP21) were investigated in guinea pig adrenal cell cultures. In untreated cells, 21-hydroxylase activity was diminished throughout a 48 h period of incubation. Although incubation with forskolin and 8Br-cAMP restored 21-hydroxylase activity to normal levels, the addition of ACTH did not prevent the decrease of 21-hydroxylase activity. Treatment of cells with RU486 for 24 h inhibited 21-hydroxylase activity by 93%; however, after removal of the drug a slight increase of enzyme activity was observed; this rise was enhanced by the addition of ACTH. Forskolin and 8Br-cAMP increased the levels of 21-hydroxylase activity to the same range as seen in untreated cells. In cells that were not pretreated with RU486, incubation with cycloheximide for 1 h had no effect on 21-hydroxylase activity and could not prevent the modest increase of 21-hydroxylase activity induced by forskolin or 8Br-cAMP after 48 h of incubation. In RU486-treated cells, cycloheximide blocks the stimulation of enzyme activity induced by ACTH, forskolin and 8Br-cAMP. Our findings indicate that 21-hydroxylase activity can be stimulated by ACTH, forskolin or 8Br-cAMP solely in the presence of reduced enzymatic activity. Western immunoblot analysis of P450c21 protein levels in untreated or RU486-treated adrenal cells indicate that P450c21 protein levels were in the same range and further incubation with ACTH caused a similar elevation of P450c21 protein levels in both the untreated and RU486-treated cells. Northern blot analysis on RNA isolated from adrenal cells showed that RU486 did not alter the basal steady state levels of P450c21 mRNA. As well, incubation with ACTH or 8Br-cAMP increased the levels of P450c21 transcript to the same extent in both untreated and RU486-treated cells. These results taken together provide additional evidence for the presence of an adrenal specific protein factor(s) modulating 21-hydroxylase activity.

Adrenal Glands↗

Reactivity to novelty during youth as a predictive factor of cognitive impairment in the elderly: a longitudinal study in rats.

A life-span study of certain behavioral traits was conducted in rats. Animals were repeatedly tested in a circular corridor for reactivity to novelty and in a recognition memory task for cognitive abilities. These measures revealed important inter-individual differences in young as well as in old subjects. Some of these differences appear with aging (memory deficits) and others disappear (high reactivity to novelty). Moreover, a relationship between high reactivity to novelty in youth and deficits in memory recognition in elderly was found. Rats that are high-responders to novelty had age-related memory impairments whereas the low-responder rats did not. While the biological mechanism linking these two behavioral traits remains to be demonstrated, this study shows that age-related impairments can be predicted by factors detectable early in life.

Aging↗

Molecular cloning and expression of guinea pig cytochrome P450c17 cDNA (steroid 17 alpha-hydroxylase/17,20 lyase): tissue distribution, regulation, and substrate specificity of the expressed enzyme.

In mammalian and fish species, P450c17 mediates both 17 alpha-hydroxylase and 17,20-lyase activities in the synthesis of steroid hormones. Previous results have shown that among the adrenal steroid hydroxylase enzymes involved in adrenal C19 steroid and glucocorticoid synthesis, regulation of cytochrome P450c17 is of primary importance because it is localized at the key branch between glucocorticoid and C19 steroid synthesis. A cDNA library from guinea pig adrenal was constructed, and the complete 17 alpha-hydroxylase cytochrome P450 cDNA was isolated. The guinea pig P450c17 cDNA includes the full-length coding region (1,524 nucleotide), the complete 3' untranslated region (169 nucleotide), and 39 bases of the 5' untranslated region. Our clone shares most of the features of the other P450c17 cDNAs; however, in addition, we identified a novel conserved region of 18 amino acids located in exon I between residues 80 and 97. This region presents the highest percentage of identity among the other P450c17 enzymes and is positioned one helixturn upstream of the important Ser106 on the corresponding human form. On Northern blot, the cDNA hybridizes with a major 1.8-kb mRNA and with two other related P450c17 mRNA of about 3 and 4 kb. P450c17 mRNA is equally distributed in male and female gonads and adrenals. Characterization of the enzymatic activity shows that 17 alpha-hydroxylase and 17,20-lyase are carried by a single protein, but in homogenates 17,20-lyase activity is barely detectable. Moreover, we demonstrate in vitro and in vivo that the guinea pig enzyme preferentially has very high levels of 17 alpha-hydroxylase and 17,20-lyase activities only toward delta 4 steroids. Second-messenger cyclic adenosine monophosphate and adrenocorticotropin specifically increased the abundance of P450c17 mRNA levels in guinea pig adrenal cells.

Adrenal Glands↗

New insights into the role of neuroactive steroids in cognitive aging.

The aim of this article is to describe neuroactive steroid research that has been focused on their physiological role in cognitive aging, an attractive new field in experimental gerontology. Neuroactive steroids have been recently proposed as biomarkers of cognitive aging, however, their specific functions have not yet been fully established. For instance, data emerging from human and animal studies suggest a complex relationship between neuroactive steroids and/or metabolites and cognitive processes during aging. Thus, a better knowledge of neuroactive steroid brain distribution and function could broaden our understanding of their physiological roles and lead to novel and more effective treatments for the management of age-related brain disorders. To this end, newly developed sensitive, specific, and accurate mass spectrometry assays may allow the quantification of neuroactive steroids in discrete brain regions and greatly contribute to unravel their role in age-related cognitive deficits.

Aged↗