Biomedical subjects

L Angelucci

Publications and source records attributed to L Angelucci.

At least 37 records · Page 2Linked to original sources

PubMed1996

Reduced hippocampal in vitro CA1 long-term potentiation in rat offsprings with increased circulating corticosterone during neonatal life.

A moderate increase in plasma level of corticosterone was induced in dams by adding the hormone (200 micrograms/ml) to the drinking water from the day after delivery to weaning. This procedure produces a parallel increase in plasma levels of the hormone in the pups (from 0.7 +/- 0.1 to 1.2 +/- 0.2 micrograms/100 ml) at 10 days of lactation. A significant (P < 0.01) reduction in the magnitude of the long-term potentiation (LTP) of the CA1 population spike occurred in hippocampal slices obtained from 30-45 day old male corticosterone-nursed rats with respect to controls, while no significant difference occurred in the magnitude of the basal CA1 evoked extracellular somatic field potentials with respect to controls. The results demonstrate that a moderate increase in plasma corticosterone during neonatal life, obtained through maternal milk, has long-lasting effects on the hippocampal CA1 synaptic plasticity. In addition, these results together with our previous findings [Catalani, A. et al., Brain Res., 624 (1993) 209-215], demonstrating that 30 day old corticosterone-nursed offsprings perform better than controls in the place learning version of the Morris water maze, show no relationships between in vitro CA1 LTP induction and spatial learning in agreement with literature data.

Animals↗

PubMed1996

Opposite strain-dependent effects of post-training corticosterone in a passive avoidance task in mice: role of dopamine.

Post-training administration of corticosterone (0.1-1 mg/kg) dose-dependently improves retention of an inhibitory avoidance response in C57BL/6 mice, whilst impairing it in the DBA/2 strain. The effects on retention performance induced by the hormone in C57BL/6 and DBA/2 mice appear to be due to an effect on memory consolidation. In fact, they were observed when the drug was given at short, but not long, periods of time after training, i.e., when the memory trace is susceptible to modulation. In the absence of pharmacological manipulations, the two strains showed a significant increase of plasma corticosterone levels 15 min after passive avoidance training that disappeared within 30 min, and similar step-through latencies on the test day. However, although no strain differences were observed for sensitivity to shock thresholds, the increase in plasma corticosterone levels elicited by passive avoidance training was more pronounced in mice of the DBA/2 strain (+160%) than in C57BL/6 mice (+52%). Moreover, DBA/2 mice were characterised by a higher number of either Type I or Type II corticosteroid receptors in the hippocampus in comparison with C57BL/6 mice. Finally, the strain-dependent effects of an intermediate dose of corticosterone were enhanced by pretreatment with either the selective D1 or D2 dopamine (DA) receptor agonists SKF 38393 and LY 171555 and reversed by pretreatment with either selective D1 or D2 DA receptor antagonists SCH 23390 and (-)-sulpiride administered at per se non-effective doses. The present results indicate that studies in inbred strains of mice can dissect opposite effects of corticosterone on memory consolidation possibly due to its action at different steps or components of the multiphasic pathway of memory consolidation. Moreover, they suggest that some of these steps involve an interaction between the hormone and brain DA system.

Animals↗

PubMed1996

Arginine-aspartate and haloperidol-induced neurobehavioral effects in the rat.

This study determined the effects, in the rat, of 8-day treatment with arginine-aspartate on haloperidol-induced catalepsy, decrease of locomotor activity and change of striatal dopamine, homovanillic acid (HVA) and dihydroxy-phenylacetic acid (DOPAC) content. Arginine-aspartate was able to attenuate the haloperidol-induced decrease of locomotor activity and to significantly reduce the catalepsy. Moreover, arginine-aspartate treatment itself increased striatal dopamine content and produced a significant decrease of the HVA/dopamine ratio. Pretreatment with arginine-aspartate was able to partially counteract the haloperidol-induced changes of dopamine metabolism: the haloperidol-induced increases of the DOPAC/dopamine and HVA/dopamine ratios were significantly reduced in arginine-aspartate- pretreated rats. These results suggest that the action of arginine-aspartate on haloperidol-induced neurobehavioral effects is probably mediated by interference with striatal dopaminergic innervation.

Animals↗

PubMed1996

Differential regulation of adrenocorticoid receptors in the hippocampus and spinal cord of adrenalectomized rats.

Using multiple polymerase chain reaction assay and cytosolic receptor binding assay we studied type I, mineralocorticoid receptor (MR), and type II, glucocorticoid receptor (GR), adrenocorticoid receptors expression in rat hippocampus and spinal cord, at various times after adrenalectomy: 12 hr, 24 hr, 3 days, and 1 week. Analysis of the data demonstrates that in hippocampus the expression of MR and GR mRNA was not significantly affected by adrenalectomy. On the contrary, Bmax of MR was significantly increased at each time post-surgery, with only slight modifications of Kd. Bmax and Kd for GR showed a significant increase after 3 days and 1 week. In the spinal cord, MR mRNA was increased 12 hr after adrenalectomy, reaching a maximum at 3 days. Bmax of MR was also significantly increased after 3 days, whereas its Kd remained unchanged for the entire duration of the the study. Both GR mRNA and binding parameters were poorly affected by adrenalectomy. The results of the present experiments demonstrate that the absence of adrenocortical hormones influences differentially MR and GR expression in hippocampus and spinal cord, suggesting the existence of various and independent mechanisms of regulation of adrenocorticoid receptor.

Adrenal Cortex Hormones↗

PubMed1996

Effects of prolonged autovehicle driving on male reproduction function: a study among taxi drivers.

This study had the purpose of exploring the possible association between the work exposures of professional drivers and their reproductive health, by studying a group of 201 taxi drivers in the city of Rome. Data on work and reproductive history were collected by interviews. Biological markers examined in 72 subjects included salivary testosterone levels, sperm quality (i.e., sperm concentration, sperm morphology, and motility), and fertility experience, including time to pregnancy. Their spermatologic profile was compared with that of a control group of 50 healthy subjects of similar age and smoking habits. The results showed that taxi drivers, compared to the controls, had a significantly lower prevalence of normal sperm forms (45.8% vs. 64.0%); this was particularly true for those with a longer time on this job. This result was confirmed by a multivariate analysis in which confounders such as age, smoking, and alcohol consumption were controlled. The other sperm parameters did not differ in the study and the control groups. Among the life-style factors, we found smoking to be associated with poorer sperm morphology. Moderate alcohol consumption was associated with a better seminologic profile, while the pattern in respect to coffee intake was inconclusive. Subjects with poor semen quality also more frequently exhibited longer time to pregnancy of their partner. The results suggest that prolonged urban automobile driving might be a risk factors for sperm quality, and particularly for sperm morphology, but the finding needs further confirmation.

Adult↗

PubMed1996

The kappa-opioid receptor agonist MR-2034 stimulates the rat hypothalamic-pituitary-adrenal axis: studies in vivo and in vitro.

There is increasing evidence that opiates not only have analgesic properties, but also regulate mechanisms activated during the stress response, such as the hypothalamic-pituitary-adrenal (HPA) axis. Indeed, opioid-containing neurons innervate the paraventricular nucleus and the median eminence, thus modulating inputs to ACTH-controlling neurons. In addition, dynorphin (the endogenous ligand of the kappa-opioid receptor)-like peptides have been found co-localized with corticotrophin-releasing hormone (CRH) and are believed to be co-secreted with it in the hypophyseal portal circulation to modulate ACTH release. In this study, we evaluated the effects of the selective kappa-opioid receptor agonist MR-2034 [(-)-N-(2-tetrahydrofurfuryl)-normetazocine] on the HPA axis in vivo and in vitro. MR-2034 was given intravenously to catheterized, freely moving, male Sprague-Dawley rats and serial blood samples were collected for ACTH and corticosterone (B) measurements. We evaluated also the site of MR-2034 action on the HPA axis in vivo, after the administration of alpha-helical CRH9-41, a CRH receptor antagonist, on hypothalamic CRH, pituitary ACTH, and B release in vitro. MR-2034 increased plasma ACTH and B levels in a dose-related fashion and this effect was antagonized by the selective kappa-opioid receptor antagonist MR-1452. In the presence of alpha-helical CRH9-41, the responses of plasma ACTH and B to MR-2034 were blunted significantly, suggesting that this compound activates the HPA axis through a CRH-dependent mechanism. Accordingly, MR-2034 stimulated hypothalamic CRH release in vitro in a concentration-dependent fashion and this effect was antagonized dose-dependently by MR-1452. However, the stimulatory effect of MR-2034 on plasma ACTH and B in vivo was not completely abolished by alpha-helical CRH9-41, suggesting that an additional, CRH-independent, mechanism was involved. Indeed, MR-2034 was able to stimulate basal ACTH output in a dose-dependent manner and this effect was antagonized by MR-1452 in vitro. On the other hand, MR-2034 did not have any effect on B release from adrenocortical cells or adrenal quarters in vitro. These results show that the benzomorphan MR-2034 stimulates the HPA axis in the rat by acting at the hypothalamic and the pituitary level. We hypothesize that endogenous kappa-opioid peptides not only act at the pituitary level to increase ACTH output, but may also act at the hypothalamic level to increase CRH release through an autocrine and/or ultrashort positive feedback mechanism.

Adrenocorticotropic Hormone↗

PubMed1995

Rat brain corticosteriod receptors are modulated by septo-hippocampal cholinergic innervation.

Brain corticosteroid receptors are regulated by neural control as well as by adrenal hormones. In this study we tested the effect of septo-hippocampal cholinergic lesions on the binding capacity of corticosteroid receptors. Rats were injected with ibotenic acid into the medial septum, and hippocampal type I and type II, and hypothalamic type II corticosteroid receptors were measured 15 days later. In lesioned animals the number of type I corticosteroid receptors in the hippocampus was increased and their affinity decreased. In the hypothalamus only an increase of type II corticosteroid receptors was observed. As expected, lesioned rats showed an increase in basal plasma corticosterone levels.

Animals↗

PubMed1995

Distribution of glucocorticoid receptor mRNA in the rat spinal cord.

Using in situ hybridization (ISH), we studied the distribution of rat glucocorticoid receptors (GR) mRNA in rat spinal cord. mRNA encoding for GR was abundant throughout the white matter and a clear pattern of distribution was detected within the grey matter. In the grey matter mRNA was primarily localized in the ventral horn, where motoneurones were strongly labelled. In the dorsal horn, the distribution appears more diffuse but the superficial layers (I and II) clearly exhibited a shigher signal. We conclude that, in rat spinal cord, GR are present in both glial and neuronal cells. In particular, both somatosensory and motor pathways contain GR.

Animals↗

PubMed1995

Age- and trauma-dependent modifications of neuromuscular junction and skeletal muscle structure in the rat. Effects of long-term treatment with Acetyl-L-Carnitine.

The influence of ageing and crushing of the sciatic nerve on the morphology of the neuromuscular junction (NMJ) and on the muscle fiber composition were studied in the rat soleus muscle using histochemical techniques associated with image analysis. The influence of a 6-month treatment with Acetyl-L-Carnitine (ALCAR, 150 mg/kg/day) on the age- and crushing-dependent changes of the NMJ and on age-related modifications of the muscle fiber composition was assessed as well. In control old and injured young rats a loss of complexity of the NMJ was observed. Treatment with ALCAR resulted in an increased endplate complexity both in old rats and in young rats injured by crushing, in comparison with respective controls. The structure of the rat soleus muscle changes with increasing age. Modification mainly consists in a type II fiber atrophy, and in the alteration of the peculiar mosaic organization of the soleus muscle fibers. In ALCAR-treated old rats, the morphology of the soleus muscle fibers was similar to that observed in adult animals. These findings suggest that treatment with ALCAR has a beneficial effect on NMJ and on muscle fiber structure in ageing or after nerve crushing. The possible mechanism of action of this 'trophic' effect of ALCAR-treatment is discussed.

Acetylcarnitine↗

PubMed1995

Neurite outgrowth in PC12 cells stimulated by acetyl-L-carnitine arginine amide.

Senescence of the central nervous system is characterized by a progressive loss of neurons that can result in physiological and behavioral impairments. Reduction in the levels of central neurotrophic factors or of neurotrophin receptors may be one of the causes of the onset of these degenerative events. Thus, a proper therapeutic approach would be to increase support to degenerating neurons with trophic factors or to stimulate endogenous neurotrophic activity. Here we report that acetyl-L-carnitine arginine amide (ST-857) is able to stimulate neurite outgrowth in rat pheochromocytoma PC12 cells in a manner similar to that elicited by nerve growth factor (NGF). Neurite induction by ST-857 requires de novo mRNA synthesis and is independent of the action of several common trophic factors. The integrity of the molecular structure of ST-857 is essential for its activity, as the single moieties of the molecule have no effect on PC12 cells, whether they are tested separately or together. Also, minor chemical modifications of ST-857, such as the presence of the arginine moiety at a position other than the amino one, completely abolish its neuritogenic effect. Lastly, the presence of ST-857 in the culture medium competes with the high affinity NGF binding in a dose dependent fashion. These results, although preliminary, are suggestive of a possible role for ST-857 in the development of therapeutic strategies to counteract degenerative diseases of the CNS.

Acetylcarnitine↗

PubMed1995

Effects of acetyl-L-carnitine treatment and stress exposure on the nerve growth factor receptor (p75NGFR) mRNA level in the central nervous system of aged rats.

1. There is growing evidence that the nerve growth factor protein (NGF), a neurotrophic factor for peripheral and central nervous system (CNS) neurons, may play a role in the modulation of the hypothalamo-pituitary-adrenocortical axis (HPAA). While NGF binding is decreased in rodent CNS after stress exposure, this reduction is prevented by treatment with Acetyl-L-Carnitine (ALCAR), a chemical substance able to prevent some degenerative events associated with aging. 2. The authors studied the effect of cold stress on the low-affinity NGF receptor (p75NGFR) mRNA levels in the basal forebrain and cerebellum of aged rats chronically treated with ALCAR. 3. The present results show that ALCAR abolished the age-associated reduction of p75NGFR mRNA levels in the basal forebrain of old animals, but did not affect the response to stress stimuli. 4. Also, treatment with ALCAR maintained p75NGFR mRNA levels in the cerebellum of old animals at levels almost identical to those observed in young control animals. 5. These results suggest a neuroprotective effect for ALCAR on central cholinergic neurons exerted at the level of transcription of p75NGFR. The restoration of p75NGFR levels could increase trophic support by NGF of these CNS cholinergic neurons which are implicated in degenerative events associated with aging.

Animals↗

PubMed1995

Acetyl-L-carnitine restores choline acetyltransferase activity in the hippocampus of rats with partial unilateral fimbria-fornix transection.

Transection of the fimbria-fornix bundle in adult rats results in degeneration of the septohippocampal cholinergic pathway, reminiscent of that occurring in aging as well as Alzheimer disease. We report here a study of the effect of a treatment with acetyl-L-carnitine (ALCAR) in three-month-old Fischer 344 rats bearing a partial unilateral fimbria-fornix transection. ALCAR is known to ameliorate some morphological and functional disturbances in the aged central nervous system (CNS). We used choline acetyltransferase (ChAT) and acetyl cholinesterase (AChE) as markers of central cholinergic function, and nerve growth factor (NGF) levels as indicative of the trophic regulation of the medio-septal cholinergic system. ChAT and AChE activities were significantly reduced in the hippocampus (HIPP) ipsilateral to the lesion as compared to the contralateral one, while no changes were observed in the septum (SPT), nucleus basalis magnocellularis (NBM) or frontal cortex (FCX). ALCAR treatment restored ChAT activity in the ipsilateral HIPP, while AChE levels were not different from those of untreated animals, and did not affect NGF content in either SPT or HIPP.

Acetylcarnitine↗

PubMed1995

Reduced glucocorticoid response to corticotropin secretagogues in the aged Sprague-Dawley rat.

Aging, as well as some frequently associated pathological conditions (depression, dementia, Alzheimer's disease, etc.), has been shown to have a profound impact on the normal functioning of the hippocampus-hypothalamo-pituitary-adrenocortical axis system. The hypothalamo-pituitary-adrenocortical axis in the aged rat is characterized by an increase in the basal level of circulating corticosterone, an impaired ability to recover from the adrenocortical stress response, and a reduced sensitivity to the dexamethasone suppression test. All these alterations may arise from a reduced hippocampal negative feedback control of the axis, as suggested by the age-dependent loss of hippocampal adrenocorticoid receptors. Among the hypothalamic corticotropin secretagogues, corticotropin-releasing hormone (CRH) and arginine-vasopressin (AVP) are considered the main physiological mediators of hypothalamic control of ACTH release. Thus, we have investigated the dynamic and the temporal course of the adrenocortical response to CRH and AVP in the aged rat. Freely moving jugular-catheterized male Sprague-Dawley rats (3- and 24-month-old) were injected with CRH (0.5, 0.05 and 0.01 microgram/kg i.v.), or AVP (1.0, 0.1 and 0.05 microgram/kg i.v.), or CRH and AVP in combination. In addition, adrenocortical sensitivity to corticotropin has been studied by injecting ACTH (10 ng/kg i.v.). Our study has (1) indicated that the response to ACTH secretagogues is dampened with aging, and (2) shown in the aged rat a slower recovery. Moreover, the results had confirmed the age-dependent increase in the basal level of corticosterone in the rat, and shown no age-related differences in the glucocorticoid response to ACTH.

Adrenocorticotropic Hormone↗

PubMed1995

Acetyl-L-carnitine in Alzheimer disease: a short-term study on CSF neurotransmitters and neuropeptides.

Acetyl-L-carnitine (ALCAR) is a drug currently under investigation for Alzheimer disease (AD) therapy. ALCAR seems to exert a number of central nervous system (CNS)-related effects, even though a clear pharmacological action that could explain clinical results in AD has not been identified yet. The aim of this study was to determine cerebrospinal fluid (CSF) and plasma biological correlates of ALCAR effects in AD after a short-term, high-dose, intravenous, open treatment. Results show that ALCAR CSF levels achieved under treatment were significantly higher than the ones at baseline, reflecting a good penetration through the blood-brain barrier and thus a direct CNS challenge. ALCAR treatment produced no apparent change on CSF classic neurotransmitters and their metabolite levels (homovanillic acid, 5-hydroxyindoleacetic acid, MHPG, dopamine, choline). Among CSF peptides, while corticotropin-releasing hormone and adrenocorticotropic hormone remained unchanged, beta-endorphins significantly decreased after treatment; plasma cortisol levels matched this reduction. Since both CSF beta-endorphins and plasma cortisol decreased, one possible explanation is that ALCAR reduced the AD-dependent hypothalamic-pituitary-adrenocortical (HPA) axis hyperactivity. At present, no clear explanation can be proposed for the specific mechanism of this action.

Aged↗

PubMed1994

Regional CNS uptake of blood-borne nerve growth factor.

Nerve growth factor (NGF), in addition to being a neurotrophic substance, has effects on the endocrine and immune systems. For example, intravenous injection of NGF results in a cascade of events leading to an increase in glucocorticoid secretion. While this response appears to be mediated centrally, there has been no evidence that circulating NGF has access to the CNS. Using intravenous injections of 125I-NGF, we find specific uptake at 1 hr but none at 6 hr, into homogenates of the basal forebrain, cerebellum, frontal cortex, hippocampus, and olfactory bulb. By autoradiography, uptake is localized to circumventricular organs, deep layers of the cerebellum, and all layers of the hippocampal region CA1, but not the dentate gyrus. Thus, uptake of blood-borne NGF could affect the hypothalamic-pituitary-adrenal axis via binding to NGF receptors present in the hippocampus. However, the sources of endogenous NGF, the mechanism of access through the blood-brain barrier, the eventual fate of NGF entering from the blood, and the physiological significance of this uptake remain to be elucidated.

Animals↗

PubMed1994

Acetyl-L-carnitine treatment increases choline acetyltransferase activity and NGF levels in the CNS of adult rats following total fimbria-fornix transection.

Transection of the fimbria-fornix in adult rats is a useful model for producing impairments of cholinergic activity in the hippocampus (HIPP) and atrophy of the medial septum cholinergic perikarya, similar to those observed during senescence, that are possibly due to the lack of nerve growth factor (NGF) retrogradely transported from the hippocampus. In our investigation we used choline acetyltransferase (ChAT) as an index of cholinergic activity in HIPP, frontal cortex (FCX), septum and nucleus basalis magnocellularis (NBM) along with measurements of NGF levels in the HIPP. Three-month-old rats with unilateral total fimbria transection received acetyl-L-carnitine (ALCAR) (150 mg/kg/day) in drinking water for 1 week before and 4 weeks after the lesion). ALCAR is a substance known to ameliorate some morphological and functional disturbances in the aging central nervous system (CNS). ChAT activity in septum and FCX, and NGF levels in HIPP were significantly increased in the treated group, compared with untreated control groups, while no changes were found in the NBM. On the other hand, a similar ALCAR treatment in unoperated animals induced an increase in ChAT activity in FCX but not in septum nor in NBM. These data are suggestive of a neurotrophic property of ALCAR exerted on those central cholinergic pathways typically damaged by aging.

Acetylcarnitine↗

PubMed1994

Acetyl-L-carnitine prevents age-dependent structural alterations in rat peripheral nerves and promotes regeneration following sciatic nerve injury in young and senescent rats.

Morphologic and morphometric alterations of the sciatic nerve from old Sprague-Dawley rats and of lesioned tibial nerve from young and senescent Sprague-Dawley rats were studied. The possible therapeutical effects of treatment with acetyl-L-carnitine (ALCAR) were also investigated, ALCAR being a compound shown to exert a beneficial pharmacological action on diabetic neuropathies. Nerve sections from animals sacrificed under anesthesia were stained with toluidine blue. In old rats, a 6-month treatment with ALCAR markedly reduced the percentage of myelinated fibers (MF) characterized by age-dependent morphologic alterations (4% in treated rats versus 11% in untreated ones), such as myelin balloons, infolded loops of myelin, myelin reduplication, and ovoids. In the lesioned animals, ALCAR-treatment (15-60 days for young rats and 6-9 months for senescent rats) produced a significant increase versus controls in the density of regenerating myelinated fibers (RMF) at 15 days (young rats) and at 30 days (senescent rats) after crush, as well as an increase in the axon diameter in both young and senescent rats at 60 days after nerve crush. The MF diameter (sheath + axons) was significantly larger in treated senescent rats than in controls at 100 days after nerve crush. In ALCAR-treated rats, both young and senescent, the density of degenerative elements was lower and the RMF ratio (RMF density/RMF density + density of degenerative elements) was higher than that in controls at all detection times.

Acetylcarnitine↗

PubMed1994

Age-dependent loss of NMDA receptors in hippocampus, striatum, and frontal cortex of the rat: prevention by acetyl-L-carnitine.

Acute i.p. administration of Acetyl-L-Carnitine (ALCAR), a component of several biological systems, has been found to modify spontaneous and evoked electrocortical activity in young rats, and, in the old rats, to improve learning ability and to increase the number of NMDA receptors in the whole brain. The present study was aimed at ascertaining the effect of chronic treatment with ALCAR added to drinking water on age-related changes in the different brain areas of rats. In twenty-four-month-old rats, ALCAR treatment for six months significantly impeded the decline in the number of NMDA receptors within the hippocampus, the frontal cortex and the striatum compared to the adult animal. This finding thus confirms the previously reported positive effect of ALCAR on the brain NMDA receptor system.

Acetylcarnitine↗