Biomedical subjects

L Angelucci

Publications and source records attributed to L Angelucci.

At least 55 records · Page 3Linked to original sources

PubMed1994

Carnitine and derivatives in the central nervous system of chick embryo.

1. Carnitine contents and the activity of carnitine acetyltransferase in the egg, in the embryo, and in different brain areas of central nervous system in chick embryo were determined in the course of development. 2. The egg showed low levels of free carnitine and acetylcarnitine. 3. In the whole embryo, at first stages of development, long chain acylcarnitine and acetylcarnitine were the best represented classes of carnitines. 4. In the brain regions acetylcarnitine levels, high at the first days, showed a continual decrease during development. 5. The activity of carnitine acetyltransferase increased and was totally related to development.

Acetylcarnitine↗

PubMed1994

Effects of concomitant nicotinic and muscarinic blockade on spatial memory disturbance in rats are purely additive: evidence from the Morris water task.

This study reexamined the role played by a concurrent manipulation of nicotinic and muscarinic acetylcholine (ACh) receptors on performance of rats in the Morris water maze. A series of experiments was performed to test decreasing doses of scopolamine, a muscarinic ACh blocker, given concurrently with a fixed dose level of mecamylamine, a nicotinic ACh blocker, down to a subthreshold combination. Both substances were also tested separately. Data were analyzed to distinguish between a summative and a greater than additive (synergistic) effect of the two blocking agents. Our results fully support the important role played by ACh systems on cognitive functions and also show the substantial functional independence of the two ACh receptors in regulating spatial learning processes. In fact, data analysis did not reveal any significant interaction between the two ACh receptor blockers other than their additive effect: the hypothesis of a reciprocal modulation between the two ACh receptors, raised by some authors, cannot be supported for spatial learning mechanisms, at least with regard to the Morris water maze paradigm.

Animals↗

PubMed1994

The hypothalamus-pituitary--adrenocortical axis: epigenetic determinants changes with aging, involvement of NGF.

In order to study the hypothesis that maternal corticosterone (B) influences the hippocampus/hypothalamus-pituitary-adrenocortical axis system in the adult rat, we induced a moderate increase in maternal plasma level of B by adding the hormone to the drinking water of the dams (200 micrograms/ml) from the day of delivery to weaning. B-nursed male rats had, at 3 months of age, a lower basal concentration of ACTH and B, as well as a lower stress (2 min restraint) induced increase. The reduced stress response was also present at 12 months. These endocrine differences were parallel to behavioural modifications. In the adult offspring of mothers that were hypercorticosteronemic during lactation, an improved spatial learning ability, a reduced emotional performance in a conflict procedure and a better performance in a conditioned active avoidance test was observed. Finally, the analysis of hippocampal adrenocorticoid receptors revealed that the postnatal endocrine manipulation induced an increase in the Type I receptor density in the adult offspring. Our findings point to an epigenetic effect of maternal B on the maturational process of the hypothalamus-pituitary-adrenocortical (HPA) axis and the hippocampus with endocrine and behavioural consequences in adulthood. The aging process has been shown to alter the normal functioning of the HPA axis. This alteration might arise from a reduced hippocampal negative feedback control, as suggested by the age-dependent loss of hippocampal adrenocorticoid receptors. Among the hypothalamic factors endowed with corticotropin secretagogue activity, corticotropin-releasing hormone (CRH) and vasopressin are considered the major physiological mediators of hypothalamic control of ACTH release.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

PubMed1994

The D1 dopamine agonist SKF 38393, but not the D2 agonist LY 171555, decreases the affinity of type II corticosteroid receptors in rat hippocampus and ventral striatum.

Type I and type II brain corticosteroid receptors are regulated by adrenal hormones as well as being under neural control. Recent studies have indicated that neurotransmitters such as serotonin and noradrenaline are also involved in the regulation of corticosteroid receptors. In a previous study, we showed that dopamine also modulates activity of the corticosteroid receptor system. In the present study, we examined the roles of the dopamine D1 and D2 receptor subtypes in the regulation of corticosteroid receptors. Adrenalectomized rats whose corticosterone levels were maintained within normal limits by corticosterone replacement implants, were injected intraperitoneally with the D1 agonist SKF 38393 or the D2 agonist LY 171555. Corticosteroid receptors were assayed in the ventral striatum and hippocampus. We have shown that the D1 agonist SKF 38393 decreased type II receptor affinity in both regions, whereas the D2 agonist LY 171555 had no effects. The results show that the influence of the dopaminergic system on corticosteroid receptors appears to be mediated by D1 receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1994

Multivariate analysis of behavioral aging highlights some unexpected features of complex systems organization.

Ten different behavioral tests were performed on a population of young (n = 20) and aged (n = 20) Fischer 344 rats. The relationship structure among these tests was studied by principal component analysis applied both to the entire data set and separately to the two age groups. This analysis proved very useful in highlighting a global index of the rat "behavioral" age based on the entire test set. The analysis effected separately on the two age groups evidenced qualitative differences between them that were linked to the different meaning the same test would assume in rats of different ages. From an overall methodological viewpoint, this work indicates that the correlations among behavioral parameters appear to depend on the observational scale and that the spin-glass model represents an appropriate metaphor to approach the study of the correlations in biological systems.

Aging↗

PubMed1993

Progeny of mothers drinking corticosterone during lactation has lower stress-induced corticosterone secretion and better cognitive performance.

In order to test the hypothesis that maternal corticosterone influences hypothalamus-pituitary-adrenal (HPA) system activity in the adult rat and behaviors related to it, we induced a moderate increase in maternal plasma level of corticosterone by adding the hormone to the drinking water of the dams (200 micrograms/ml) from the day after delivery to weaning. Our previous experiments have shown that this procedure produces plasma levels of the hormone in the range of those following a mild psychic stress (from 4.3 +/- 0.5 to 9.5 +/- 1.8 micrograms/100 ml in the dams, and from 0.7 +/- 0.1 to 1.2 +/- 0.2 micrograms/100 ml in the pups at 10 days of lactation). Adrenal weights were slightly and temporarily decreased by treatment in both mothers and offspring. Only the male progeny was investigated in this study. Corticosterone-nursed rats had significantly less corticosterone and ACTH in basal conditions and after a 2 min restraint stress at 3 months of age, and showed better performances at weaning and at 1, 2 and 3 months of life in the Morris water maze. Our results demonstrate that a moderate increase in maternal corticosterone during lactation influences the activity of HPA axis and improves spatial learning ability of the adult offspring.

Adrenal Glands↗

PubMed1993

Basal and stress-induced corticosterone secretion is decreased by lesion of mesencephalic dopaminergic neurons.

There is evidence that certain psychopathological conditions are accompanied by a dysfunction in both the hypothalamo-pituitary-adrenal axis and dopaminergic systems, although the relationship between these two systems is as yet unclear. In the present study we investigated the effect of a specific lesion of dopamine mesencephalic neurons (Ventral Tegmental Area) on basal and stress-induced corticosterone secretion. Three weeks after injection of 6-OHDA, there was a depletion in dopamine in the frontal cortex and in the ventral and dorsal striatum, whereas norepinephrine and serotonin levels were unchanged. The dopamine-lesioned rats exhibited a lower basal and stress-induced corticosterone secretion than the sham-lesioned animals. The results indicate that the dopaminergic system may have a stimulatory influence on the hypothalamo-pituitary-adrenal axis.

Animals↗

PubMed1993

Nerve growth factor and p75NGFR factor receptor mRNA change in rodent CNS following stress activation of the hypothalamo-pituitary-adrenocortical axis.

The synthesis of nerve growth factor (NGF) by the hippocampus raises the possibility that NGF may play a role in the regulation of the hypothalamic-pituitary-adrenal axis (HPAA). Subchronic cold stress has been shown to activate the HPAA in a mild noninvasive manner, to stimulate serum glucocorticoid levels, and to perturb NGF binding in hippocampus and basal forebrain. One or repeated episodes of cold stress increased NGF mRNA levels in the hippocampus and p75NGFR mRNA levels in the basal forebrain. These changes were not due to elevated serum glucocorticoid levels since treatment with exogenous corticosterone had no effect on NGF and p75NGFR mRNA levels. Adrenalectomy did not prevent the stress induced increases in NGF and p75NGFR mRNA.

Adaptation, Physiological↗

PubMed1993

Synthesis and amnesia-reversal activity of a series of 7- and 5-membered 3-acylamino lactams.

A series of 3-(acylamino)-epsilon-caprolactams and 3-(acylamino)-2-pyrrolidinones was synthesized. Some of these compounds reversed at different degrees electroconvulsive shock- and Scopolamine-induced amnesia, using a step-through passive avoidance in mice. Classical nootropic drugs, i.e., Aniracetam, Oxiracetam, and Piracetam, were used as reference compounds. Within the analyses of data performed, we introduced a new parameter, the confrontation index (CI), which is a function of Mann-Whitney's U statistic. The CI permits a common scale of activity of substances to be generated, independently of probabilistic hypotheses, with higher scores representing higher activities. The most active compounds were characterized by the formylamino and [3-(trifluoromethyl)benzoyl]amino groups in the 3-position of the ring. None of the substances assayed showed any effect on spontaneous behavior and neurovegetative system.

Amnesia↗

PubMed1993

The mesolimbic dopaminergic system exerts an inhibitory influence on brain corticosteroid receptor affinities.

Central type I and type II corticosteroid receptors play a principle role in the regulation of corticosterone secretion. Although the binding capacity of these receptors is thought to be regulated essentially hormonally, there is also evidence for a direct neural control. For example, experimental manipulation of central serotoninergic and noradrenergic activities modifies the binding capacity of type I and type II corticosteroid receptors via a corticosterone-independent mechanism. In this study, we tested the effect of lesions of dopaminergic neurons in the ventral tegmental area on corticosteroid receptor binding capacity. The study was performed in adrenalectomized rats whose corticosterone levels were maintained within normal limits by corticosterone pellets and corticosterone in their drinking water during the dark period to generate the circadian rhythm. Binding properties of corticosteroid receptors were analysed in target regions of the lesioned neurons, including the ventral and dorsal striatum. Corticosteroid receptors in the hippocampus were also studied as a control as these lesions do not significantly affect dopamine content in this structure. Three weeks after the lesion, type II corticosteroid receptor affinity was increased in the ventral striatum. There was no effect on receptors in the dorsal striatum or hippocampus. Our results, together with other reports showing that dopamine inhibits the expression of corticosteroid receptors in the anterior pituitary, suggest that dopamine transmission exerts a negative control on central corticosteroid receptors.

Adrenalectomy↗

PubMed1993

Brain adrenocorticoid receptor binding capacity in the diabetes insipidus brattleboro rat is dependent on maternal genotype.

We examined whether a different maternal genotype might differentially affect the brain adrenocorticoid receptor in homozygous diabetes insipidus Brattleboro rats. Two distinct homozygous diabetic offsprings were studied in comparison with Long Evans (LE) rats: one born of a homozygous mother (DI/HOM MOTHER), and the other born of a heterozygous mother (DI/HET MOTHER). The number of type I adrenocorticoid receptors of DI/HET MOTHER rats was significantly lower than that of LE rats in the hippocampus and hypothalamus, while in the amygdala both type I and type II receptors decreased. Surprisingly, the binding capacity of DI/HOM MOTHER rats, notwithstanding the absence of vasopressin (VP), as in the DI/HET MOTHER, did not differ from that of LE. Superimposable results were obtained in all the brain regions examined. No differences in binding affinity values (Kd) were detected. It was hypothesized that an 'unknown factor' linked to the genotype of the homozygous diabetic mother might counterbalance the receptor deficit otherwise induced by the lack of VP. The existence of two subpopulations of diabetic Brattleboro rats, as used in this study, should prompt to reexamine the origins of some behavioral and endocrine discrepancies appearing in studies on the homozygous diabetes insipidus Brattleboro strain.

Amygdala↗

PubMed1993

Hypothalamic involvement in the activation of the pituitary-adrenocortical axis by nerve growth factor.

Intravenous injection of nerve growth factor (NGF) into rats produces a dose-dependent (from 0.1 to 5 nmol/kg) increase in circulating concentrations of adrenocorticotropin (ACTH) and corticosterone. We have investigated whether this effect is produced through a direct action on a component of the hypothalamo-pituitary-adrenocortical axis. NGF (50 and 500 nM), added to the incubation medium of in vitro isolated pituitary segments or dispersed adrenal cells, did not modify either basal and stimulated release of biologically active or immunoreactive ACTH or release of corticosterone, respectively. The presence of NGF in the incubation medium of in vitro isolated hypothalami produced a dose-dependent (from 150 to 600 nM) increase of both release and content of some material with corticotropin-releasing bioactivity. The nature of this corticotropin-releasing bioactivity was determined directly by radioimmunoassays. Results have indicated that NGF induced an increase of both release and content of hypothalamic arginine-vasopressin (AVP), while no changes were observed in the release and content of hypothalamic corticotropin-releasing hormone (CRH). These results suggest that adrenocortical stimulation by NGF in vivo could be mediated by the release of hypothalamic AVP rather than CRH. The finding that in vivo NGF stimulatory effect was not abolished by the specific CRH antagonist alpha-helical CRH(9-41), while it was accompanied by an increase in circulating AVP levels, supports this interpretation. However, the fact that the hypothalamus is stimulated in vitro by NGF concentrations higher than those expected to reach this structure after systemic injection of active doses raises the possibility that other brain areas such as the hippocampus participate in NGF-induced adrenocortical activation.

Adrenal Cortex↗

PubMed1992

Noradrenergic regulation of type-I and type-II corticosteroid receptors in amygdala and hypothalamus.

The effects of glucocorticoids on various brain functions including the negative feedback control of HPA axis are mediated by two types of receptor (type I or mineralocorticoid and type II or glucocorticoid) in the central nervous system. Furthermore, noradrenergic systems have been showed to stimulate the activity of hypothalamo-pituitary-adrenal (HPA) axis. The neural and receptor controls of HPA axis activity are generally thought to be independent. Although receptor numbers, especially type-II receptors, are thought to be regulated by circulating levels of corticosterone, they may also be under direct neural control. Thus, it may be suggested that these two types of control are functionally related and that noradrenergic systems may affect HPA axis activity either directly or indirectly via change in receptor characteristics. A major problem in the interpretation of studies examining neurotransmitter regulation of corticosteroid receptors is that the effects of drugs or brain lesions on receptors levels may be secondary to their effects on adrenocortical function. In order to demonstrate a neuronal control on corticosteroid receptors, we tested the effect of 6-hydroxydopamine lesion of noradrenergic systems in the pedunculus cerebellaris superior in adrenalectomized animals whose corticosterone levels were maintained within normal limits by corticosterone replacement implants. Both types of receptor were assayed in hypothalamus and amygdala. We show that: (1) corticosteroid receptors are influenced by noradrenergic systems; (2) this effect depends on the brain region and the receptor type. After the noradrenergic lesion type-I receptors were reduced in hypothalamus and amygdala, whereas type-II receptor were only increased in hypothalamus while receptor affinities were unaltered.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗

PubMed1992

Stimulation of nerve growth factor receptors in PC12 by acetyl-L-carnitine.

Acetyl-L-carnitine (ALCAR) prevents some deficits associated with aging in the central nervous system (CNS), such as the aged-related reduction of nerve growth factor (NGF) binding. The aim of this study was to ascertain whether ALCAR could affect the expression of an NGF receptor (p75NGFR). Treatment of PC12 cells with ALCAR increased equilibrium binding of 125I-NGF. ALCAR treatment also increased the amount of immunoprecipitable p75NGFR from PC12 cells. Lastly, the level of p75NGFR messenger RNA (mRNA) in PC12 was increased following ALCAR treatment. These results are in agreement with the hypothesis that there is a direct action of ALCAR on p75NGFR expression in aged rodent CNS.

Acetylcarnitine↗

PubMed1992

Repeated stressful experiences differently affect limbic dopamine release during and following stress.

The effects of repeated restraint stress exposures (daily 60 min, for 6 days) on extracellular dopamine in the nucleus accumbens, during and after the stress experience, have been investigated in rats by in vivo microdialysis. On the first day, restraint increased dopamine release during the first 40 min followed by a return to basal levels (50-60 min later). As soon as restraint ceased and the rats were set free, there was another increase in dopamine release lasting 40 min. On the second and third day, restraint produced only a slight increase in dopamine release, while no significant changes were evident from the fourth to the sixth day. By contrast, from the second to the sixth day the increase in dopamine release observed once rats were freed, was unchanged in comparison to the first day. The present results show that the activation of the mesolimbic dopaminergic system induced by aversive stimuli adapts to repeated experiences differently from that produced by pleasurable events, suggesting that aversive and rewarding experiences involve different neural systems.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1992

Spatial memory in aged rats: population heterogeneity and effect of levocarnitine acetyl.

The existence in a population of aging rats of classes that display a different performance in the Morris water-maze test was investigated by cluster analysis procedure. These classes identified at 18 months of age showed a different response to levocarnitine acetyl and had a different behavioral profile when tested at 25 months of age. These findings demonstrate the need for an alternative interpretation of variability in animal populations as measured by the standard statistical analyses. The data analysis strategy we propose here will allow for the use of variability as a useful source of information.

Acetylcarnitine↗

PubMed1992

Effects of acute and repeated exposure to stress on the hypothalamo-pituitary-adrenocortical activity in mice during postnatal development.

Hypothalamo-pituitary-adrenocortical (HPA) response to a mild stressful procedure was investigated in mice at Days 8, 10, 12, and 14 of postnatal development. Pups that were removed from the dam and exposed to a novel odor (clean bedding) for 15 min showed higher plasma corticosterone levels than pups whose mother was removed from the cage for 15 min or unhandled pups at all ages, although statistically significant differences were only evident at Days 12 and 14. Lower HPA axis responding in younger mice was not due to immaturity since 8-day-old mice showed a significant and larger increase of plasma corticosterone levels when separated from the mother and isolated from littermates in the absence of bedding. Mice daily exposed to clean bedding (15 min) for the first 13 days of life did not show reduced plasma corticosterone response when reexposed to the stressor at 14 days of age. Conversely, increased plasma corticosterone levels in dams in response to removal of pups was not detectable after repeated exposure to this manipulation (14 days) regardless of the procedure their pups were submitted to, thus ruling out a role of maternal corticosterone passing through the milk on which the pups were fed. These results demonstrate that 15 min exposure to clean bedding is a noninvasive procedure able to elicit HPA axis response in developing mice over a wide age range without producing habituation.

Animals↗

PubMed1992

Active avoidance learning in old rats chronically treated with levocarnitine acetyl.

The aging laboratory animal is recognized as a suitable experimental model for the investigation on drugs potentially able to retard the age-dependent decline in cognitive functions. There is robust evidence that levocarnitine acetyl (ALCAR), the acetyl derivative of carnitine, when administered chronically, prevents some age-related deficits of the central nervous system, mainly at the hippocampal level. On the basis of this evidence and because learning of active avoidance was demonstrated to become impaired with age, we decided to investigate the effect of ALCAR in rats. For statistical evaluation of results, the Cluster Analysis technique was chosen. This procedure pointed out the great heterogeneity of the old population and allowed the classification of the animals into homogeneous groups according to their response pattern. The effect of ALCAR was evident in the higher number of treated old animals yielding escape responses, indicating that ALCAR can preserve, at least partially, learning and memory from the natural decay occurring with age.

Acetylcarnitine↗