Biomedical subjects

M Darnaudéry

Publications and source records attributed to M Darnaudéry.

7 recordsLinked to original sources

PubMed1999

Prenatal stress alters circadian activity of hypothalamo-pituitary-adrenal axis and hippocampal corticosteroid receptors in adult rats of both gender.

Prenatal stress impairs activity of the hypothalamo-pituitary-adrenal (HPA) axis in response to stress in adult offspring. So far, very few data are available on the effects of prenatal stress on circadian functioning of the HPA axis. Here, we studied the effects of prenatal stress on the circadian rhythm of corticosterone secretion in male and female adult rats. To evaluate the effects of prenatal stress on various regulatory components of corticosterone secretion, we also assessed the diurnal fluctuation of adrenocorticotropin, total and free corticosterone levels, and hippocampal corticosteroid receptors. Finally, in the search of possible maternal factors, we studied the effects of repeated restraint stress on the pattern of corticosterone secretion in pregnant female rats. Results demonstrate that prenatal stress induced higher levels of total and free corticosterone secretion at the end of the light period in both males and females, and hypercorticism over the entire diurnal cycle in females. No diurnal fluctuation of adrenocorticotropin was observed in any group studied. The effects of prenatal stress on corticosterone secretion could be mediated, at least in part, by a reduction in corticosteroid receptors at specific times of day. Results also show that prepartal stress alters the pattern of corticosterone secretion in pregnant females. Those data indicate that prenatally stressed rats exhibit an altered temporal functioning of the HPA axis, which, taken together with their abnormal response to stress, reinforces the idea of a general homeostatic dysfunction in those animals.

Adrenocorticotropic Hormone↗

PubMed1999

The promnesic neurosteroid pregnenolone sulfate increases paradoxical sleep in rats.

The effect of systemic administration of the neurosteroid pregnenolone sulfate (PREG-S) on sleep-wakefulness cycle and on spatial memory performances was investigated in male Sprague-Dawley rats. In the first experiment, the effect of PREG-S administration (saline, 4.75, 47.5 mg/kg, i.p.) on 24 h EEG recording was evaluated. In the second experiment, spatial memory performance in a two-trial memory task was evaluated after post-acquisition administration of similar doses of PREG-S as in the first experiment. Results show that PREG-S increases paradoxical sleep and improves the performance on the memory task yielding similar dose response curves. Starting 4 h after administration of 47.5 mg/kg PREG-S, paradoxical sleep is increased for 10 h. The PREG-S effect on spatial memory lasts for at least 24 h after injection. These results suggest that an enhancement of paradoxical sleep may be involved in the promnesic effects of this neurosteroid.

Animals↗

PubMed1999

Infusion of neurosteroids into the rat nucleus basalis affects paradoxical sleep in accordance with their memory modulating properties.

The neurosteroids pregnenolone sulfate and allopregnanolone affect memory processes in an opposite manner, pregnenolone sulfate acts as a potent memory-enhancer whereas allopregnanolone impairs memory performance. The mechanisms underlying these memory modulating properties have yet to be elucidated. We have previously reported that infusions of either neurosteroid into the nucleus basalis magnocellularis, one of the main forebrain cholinergic nuclei, differentially affect spatial memory in rats. The relationships between memory performance and paradoxical sleep are well documented, therefore we investigated whether neurosteroids infused into the nucleus basalis magnocellularis affected the sleep-wakefulness cycle in rats, measured by electroencephalographic recordings. Results show that pregnenolone sulfate (5 ng) increased by 12%, whereas allopregnanolone (2 ng) decreased by 24%, the duration of paradoxical sleep in the 24 h interval following injection compared to control recordings. Pregnenolone sulfate inhibits GABA(A) receptors whereas allopregnanolone stimulates them. Since cholinergic neurons of the nucleus basalis magnocellularis are GABA-modulated, it may be postulated that these neurosteroids modify paradoxical sleep by acting on the cholinergic transmission. This may account, at least in part, for the memory modulating properties of these compounds.

Animals↗

PubMed1998

The neurosteroid pregnenolone sulfate infused into the nucleus basalis increases both acetylcholine release in the frontal cortex or amygdala and spatial memory.

The effects of an infusion (5 ng) of the neurosteroid pregnenolone sulfate into the nucleus basalis magnocellularis on acetylcholine release in the frontoparietal cortex and basolateral amygdala were evaluated during the 130 min post-injection in male Sprague-Dawley rats using in vivo microdialysis coupled "on line" with high performance liquid chromatography detection. One week later, the same animals were tested for spatial memory after another infusion of pregnenolone sulfate (5 ng) into the nucleus basalis. Results show that pregnenolone sulfate enhanced acetylcholine release by more than 50% of baseline concentrations in the two structures relative to a control injection. The duration of this effect was longer in cortex (130 min) than in amygdala (30 min). Furthermore, pregnenolone sulfate improved memory performance in a task based upon spatial recognition of a familiar environment. A significant positive correlation (r=0.49) was found between the recognition score in the spatial memory test and the levels of acetylcholine release in the frontoparietal cortex but not in the basolateral amygdala. Therefore, our results suggest that the nucleus basalis magnocellularis-cortical pathway could be in part responsible for the promnesic effect of pregnenolone sulfate. This neurosteroid acts as a negative modulator of the GABA(A) receptor complex and positively modulates the N-methyl-D-aspartate receptor, possibly resulting in a global stimulatory effect on central cholinergic neurotransmission.

Acetylcholine↗

PubMed1998

The neurosteroid pregnenolone sulfate increases cortical acetylcholine release: a microdialysis study in freely moving rats.

The effects of pregnenolone sulfate (Preg-S) administrations (0, 12, 48, 96, and 192 nmol intracerebroventricularly) on acetylcholine (ACh) release in the frontal cortex and dorsal striatum were investigated by on-line microdialysis in freely moving rats. Following Preg-S administration, extracellular ACh levels in the frontal cortex increased in a dose-dependent manner, whereas no change was observed in the striatum. The highest doses (96 and 192 nmol) induced a threefold increase above control values of ACh release, the intermediate dose of 48 nmol led to a twofold increase, whereas after the dose of 12 nmol, the levels of ACh were not different from those observed after vehicle injection. The increase in cortical ACh reached a maximum 30 min after administration for all the active doses. Taken together, these results suggest that Preg-S interacts with the cortical cholinergic system, which may account, at least in part, for the promnesic and/or antiamnesic properties of this neurosteroid.

Acetylcholine↗

PubMed1997

Neurosteroids: deficient cognitive performance in aged rats depends on low pregnenolone sulfate levels in the hippocampus.

Pregnenolone sulfate (PREG S) is synthesized in the nervous system and is a major neurosteroid in the rat brain. Its concentrations were measured in the hippocampus and other brain areas of single adult and aged (22-24 month-old) male Sprague-Dawley rats. Significantly lower levels were found in aged rats, although the values were widely scattered and reached, in about half the animals, the same range as those of young ones. The spatial memory performances of aged rats were investigated in two different spatial memory tasks, the Morris water maze and Y-maze. Performances in both tests were significantly correlated and, accompanied by appropriate controls, likely evaluated genuine memory function. Importantly, individual hippocampal PREG S and distance to reach the platform in the water maze were linked by a significant correlation, i.e., those rats with lower memory deficit had the highest PREG S levels, whereas no relationship was found with the PREG S content in other brain areas (amygdala, prefrontal cortex, parietal cortex, striatum). Moreover, the memory deficit of cognitively impaired aged rats was transiently corrected after either intraperitoneal or bilateral intrahippocampal injection of PREG S. PREG S is both a gamma-aminobutyric acid antagonist and a positive allosteric modulator at the N-methyl-D-aspartate receptor, and may reinforce neurotransmitter system(s) that decline with age. Indeed, intracerebroventricular injection of PREG S was shown to stimulate acetylcholine release in the adult rat hippocampus. In conclusion, it is proposed that the hippocampal content of PREG S plays a physiological role in preserving and/or enhancing cognitive abilities in old animals, possibly via an interaction with central cholinergic systems. Thus, neurosteroids should be further studied in the context of prevention and/or treatment of age-related memory disorders.

Aging↗

PubMed1997

Decrease in highly polysialylated neuronal cell adhesion molecules and in spatial learning during ageing are not correlated.

Age-dependent spatial memory impairments have been related to a decline in hippocampal plasticity. Highly polysialylated neuronal cell adhesion molecules (PSA-NCAM) show a strong expression during adulthood within regions associated with neuroplastic events. Furthermore, NCAM molecules have been proposed to mediate neuronal plasticity during learning and memory. The aim of the present study was to examine the effect of ageing on the expression of PSA-NCAM within the hippocampus. To investigate whether age-dependent changes in expression of PSA-NCAM were accentuated in aged rats with learning impairment, animals were in a first step assessed for their cognitive abilities using a Morris water maze. Seven-month-old and 24-month-old-rats were tested for their performance in the Morris water maze. The animals were sacrificed and brain sections were processed for PSA-NCAM immunohistochemistry. Ageing was accompanied by an overall decrease in PSA-NCAM-immunoreactivity (-IR) within the forebrain, presenting a important decrease of the number of PSA-NCAM-IR perikarya within the hippocampus. These results were confirmed by Western blot analysis. No difference in PSA-NCAM immunoreactivity was observed in aged rats with or without spatial learning impairment. It is concluded that although changes in PSA-NCAM accompanied the decrease in cognitive abilities, our data did not evidence a causal relationship between these two parameters.

Aging↗