Biomedical subjects

M Fusco

Publications and source records attributed to M Fusco.

At least 37 records · Page 2Linked to original sources

PubMed1993

Fos induction by nerve growth factor in the adult rat brain.

The distribution of Fos, the protein product of the immediate early gene c-fos, was studied with immunocytochemistry in the adult male rat brain after nerve growth factor (NGF) administration. NGF was injected in the lateral cerebral ventricle through a previously implanted cannula. The total number of Fos-immunoreactive (ir) neurons in the brain was 2-3 times higher after NGF administration than in control animals (untreated or injected with cytochrome c). With respect to control rats, in the NGF-treated cases Fos-ir cells were more numerous in the anterior olfactory nucleus, in the medial prefrontal and anterior cingulate cortices, in the basal forebrain, in the preoptic and ventromedial nuclei of the hypothalamus, as well as anterior hypothalamic area, in the thalamic midline nuclei, and in some brainstem structures, such as the parabrachial nucleus. The relative quantitative increase of Fos-ir neurons varied in the different structures. In addition, Fos-ir neurons were evident after NGF administration in areas devoid of immunopositive cells in control animals. These included: frontoparietal and occipital cortical fields, the hypothalamic arcuate nucleus, and many brainstem structures, such as the dorsal nucleus of the lateral lemniscus, posterodorsal tegmental, medial and lateral vestibular, ventral cochlear, and prepositus hypoglossal nuclei. These findings demonstrate that the intracerebroventricular administration of NGF can induce c-fos expression in neurons in vivo. The distribution of Fos-ir neurons indicates that NGF can induce activation of functionally and chemically heterogeneous neuronal subsets in the brain.

Animals↗

PubMed1993

Gangliosides and neurotrophic factors in neurodegenerative diseases: from experimental findings to clinical perspectives.

A large body of experimental data suggests that neurotrophic molecules and/or substances that facilitate their action could be pharmaceutical agents for neurodegenerative pathologies. In particular, it has been demonstrated that nerve growth factor (NGF) exerts a physiological role for forebrain cholinergic neurons, while brain-derived neurotrophic factor (BDNF) seems to play a relevant role in rescuing dopaminergic neurons following damage. In addition, gangliosides are reported to potentiate neurotrophic factor effects in vitro as well as in vivo. In this study we examined the effects of the monosialoganglioside GM1 in different experimental models. The responsiveness of forebrain cholinergic neurons following NGF +/- GM1 was evaluated by assessing choline acetyltransferase (ChAT) activity in hippocampus, septal area and striatum of behaviorally impaired 24-month-old rats. NGF was intracerebroventricularly (i.c.v.) infused for 2 weeks while GM1 was given systemically for 3 weeks, starting from the beginning of NGF infusion. Moreover, the possible protective effects of GM1 were assessed following exposure of cultured cerebellar granule cells and dopaminergic mesencephalic neurons to different doses of 6-OH-DOPA, a metabolite of the dopamine pathway which has excitotoxic properties and has been hypothesized to participate in the pathology of Parkinson's disease. GM1 treatment to aged rats was seen to potentiate the NGF-induced increase of ChAT activity in the striatum ipsilateral to the NGF infusion. Moreover, in the striatum contralateral to the NGF infusion, GM1 increased ChAT activity above the control values, whereas NGF treatment alone did not affect enzymatic activity. GM1 treatment of cerebellar granule cells and mesencephalic neurons counteracted the dose- and time-dependent neurotoxicity of 6-OH-DOPA. These data support the notion that GM1 might prove useful in treating those pathological conditions where trophic factor deficits and/or excitotoxin-related toxicity play an important role.

Aging↗

PubMed1992

Nerve growth factor modulates the expression of muscarinic cholinergic receptor messenger RNA in telencephalic neuronal cultures from newborn rat brain.

The effect of nerve growth factor (NGF) on muscarinic receptor subtypes was investigated in a primary culture of telencephalic neurons prepared from neonatal rats. The treatment with 100 ng/ml of NGF significantly enhanced choline acetyltransferase (ChAT) activity and intracellular acetylcholine (ACh) content during cultivation. The same treatment induced an early transient increase of the number of muscarinic cholinergic receptors (mAChR), as measured by [3H]quinuclidinyl benzilate binding to cell homogenate, that was followed by a dramatic decrease of the receptor density from the 9th day of culture. Atropine completely prevented the decrease of the maximal number of muscarinic recognition sites induced by NGF. Prolonged exposure of telencephalic neurons to NGF also induced a significant reduction of the relative content of the messenger RNA (mRNA) encoding m1 and m3 receptors, while the m4 transcript was increased by the treatment. We suggest that the prolonged stimulation of cholinergic neurons by NGF induces a downregulation of m1 and m3 mAChR and their mRNAs on the postsynaptic site, while it increases the synthesis of the functionally distinct m4 receptor subtype, which might be presynaptically localized on cholinergic neurons. The transient increase of the receptor number that occurs at the first days of culture was not paralleled by changes in the relative content of mAChR mRNAs and might be associated with the trophic activity of NGF on cholinergic synapses during early development.

Animals↗

PubMed1992

In vivo activated brain astrocytes may produce and secrete nerve growth factor-like molecules.

The cellular localization of the nerve growth factor-like immunoreactivity (NGF-LIR) has been studied in the septum and hippocampus of the rat brain 7 days following partial electrolytic lesion (2 mA, 30 s) of the septohippocampal pathways or after single intraventricular administration of 15 U of interleukin-1 beta (IL-1 beta). A double immunostaining technique which allowed a simultaneous localization of NGF-LIR and that of astroglia marker glial fibrillary acidic protein was used. Our data show that after both treatments, apart from neuronal localization of NGF-LIR typical for normal brain, many astrocytes both in the septum and hippocampus became NGF-like immunoreactive. Besides, NGF-LIR often formed a "halo" reaction around astrocytes. These results support the notion that activated in vivo brain astrocytes may, just as astrocytes growing in vitro, synthesize and secrete NGF-like molecules. Our findings may be of importance in considerations concerning trophic support to the cholinergic neurons of the basal forebrain nuclei whose impaired function is essentially responsible for some cognitive deficits in neurodegenerative diseases such as Alzheimer disease.

Animals↗

PubMed1992

Depressed nocturnal plasma melatonin levels in drug-free paranoid schizophrenics.

The 24-h profiles of plasma melatonin and cortisol were evaluated in 7 drug-free male paranoid schizophrenics and in 7 healthy subjects matched to the patients for age, sex, body weight, height and season of testing. Blood samples were obtained at 20.00, 22.00, 24.00, 01.00, 02.00, 06.00, 08.00 and 12.00 h. Light was turned off from 21.00 to 07.00 h. Compared with that of the normal controls, the circadian rhythm of plasma melatonin was absent in paranoid schizophrenics (F7.84 = 7.30, p less than 0.0001; two-way ANOVA with repeated measures) whereas the 24-h profile of plasma cortisol was preserved, although at a slightly higher level (F1.12 = 26.810, p less than 0.0002). The melatonin/cortisol ratio was significantly higher in healthy subjects than in the schizophrenic patients. A functional relationship between disturbances in the melatonin rhythm especially and schizophrenia may be proposed, although the significance of this relationship remains to be elucidated.

Adult↗

PubMed1992

Cellular localization of nerve growth factor-like immunoreactivity in hippocampus and septum of adult rat brain.

The cellular localization of the nerve growth factor-like immunoreactivity (NGF-LIR) has been studied in the intact adult rat brain at the level of the hippocampus and the septum. Immunolabelling for NGF combined with counterstaining with cresyl violet and double immunostaining technique, which allowed simultaneous localization of NGF-LIR and that of astroglial marker -GFAP, were used. The data indicate neuronal localization of NGF-like immunoreactivity and a lack of colocalization of NGF-LIR with the immunoreactivity of GFAP in the hippocampus. These data are consistent with in situ hybridization results for NGF and immunocytochemical results for pro-NGF localization obtained by others. At the septal level, apart from neuronal localization of NGF-LIR, single NGF-like immunoreactive astrocytes have been observed. This suggests that, although to a very small extent, in vivo intact brain astrocytes may, just as astrocytes growing in vitro, synthesize NGF-like molecules. This finding may be of importance in better understanding the trophic support for NGF responsive cholinergic neurones in the brain.

Animals↗

PubMed1991

Nerve growth factor differentially modulates the expression of its receptor within the CNS.

The effect of nerve growth factor on the expression of nerve growth factor receptor in the central nervous system of newborn and adult rats was studied by means of immunohistochemistry with the monoclonal antibody 192-IgG. Both during development and in adulthood, the intracerebroventricular administration of nerve growth factor elicited a pronounced increase of nerve growth factor receptor-like immunoreactivity in the cell bodies and neural processes of the basal forebrain cholinergic nuclei, as compared to cytochrome c-treated rats (controls). A pronounced nerve growth factor-induced increase of nerve growth factor receptor-like immunoreactivity was also observed in central regions innervated by trigeminal and spinal ganglia. A moderate to a marked increase of nerve growth factor receptor-like immunoreactivity was evident in some mesencephalic visual system-related structures and thalamic nuclei expressing nerve growth factor receptor. In contrast, NGF treatment did not induce appreciable modification of nerve growth factor receptor-like immunoreactivity in cerebellar, brainstem, and spinal motor structures of newborn rats. In adult nerve growth factor-treated rats, a decrease of nerve growth factor receptor-like immunoreactivity was detected in the cerebellum, whereas no re-expression of nerve growth factor receptor-like immunoreactivity occurred in the motor structures that had expressed it in the first postnatal week. Finally, nerve growth factor was also found to enhance, in both adult and newborn rats, nerve growth factor receptor-like immunoreactivity associated with ependymal and subependymal cellular elements of the lateral and third ventricles, as well as with the leptomeninges overlying the superior colliculus and supraoptic area. The present results indicate that endogenous nerve growth factor or nerve growth factor-like molecules may play a dynamic role in a variety of cell populations of both the developing and mature mammalian central nervous system. We thus propose the nerve growth factor ability to modulate its receptor in vivo as a novel criterion to define nerve growth factor or nerve growth factor-like molecules, sensitive neuronal, and non-neuronal cells. Whereas this criterion does not intrinsically possess absolute physiological validity, its pharmacological concomitants might be relevant in view of the proposed therapeutical use of this trophic factor.

Aging↗

PubMed1991

Choline acetyltransferase messenger RNA expression in developing and adult rat brain: regulation by nerve growth factor.

The polymerase chain reaction (PCR) was used to develop a method for detection and relative quantification of the choline acetyltransferase (ChAT) mRNA in neonatal and adult rat CNS. Oligonucleotide primers derived from a porcine ChAT cDNA sequence were used in coupled reverse transcriptase (RT)-PCR to amplify a cDNA sequence of 206 bp which arises in a cycle- and RNA-dependent manner and which hybridizes with both an internal oligonucleotide and a ChAT cDNA probe. ChAT mRNA was detected in spinal cord, septal area, striatum, cortex and hippocampus but not in cerebellum and cardiac or skeletal muscle. In the septal area, relative quantitative evaluation of ChAT mRNA levels by RT-PCR indicates that this transcript is developmentally regulated and increased following intracerebral administration of nerve growth factor (NGF) to both neonatal and young adult rats. This suggests that the increases of ChAT activity observed in basal forebrain during development or after NGF administration are, at least in part, associated with an increase in corresponding levels of mRNA.

Aging↗

PubMed1991

Failure of single electroconvulsive shock to affect daytime melatonin production in rats.

It has been reported that, in the rat, different types of stressful procedures increase daytime melatonin production. Electroconvulsive shock (ECS) has been shown not to affect daytime pineal melatonin in rats killed 9 hr after its administration. It is possible that the long-lasting interval between the ECS administration and the sacrifice of the animals obscured an effect of the stressful procedure. In the present study, the effects of acute ECS on daytime melatonin production were evaluated in both ECS- and sham-treated rats killed 30, 60, 120, and 240 min after treatment. As compared with the sham-treated animals, rats receiving acute ECS (80 mA, 0.5 sec) did not show any significant difference in either pineal or serum melatonin levels at any time point after treatment. These data indicate that single ECS does not affect daytime melatonin production in the rat and suggest that the pineal gland may respond differently to the various stressful procedures.

Analysis of Variance↗

PubMed1990

Physical exercise at night blunts the nocturnal increase of plasma melatonin levels in healthy humans.

The effects of physical exercise on nighttime melatonin secretion have never been investigated in humans. For this purpose, plasma melatonin levels were measured at different times during the day and the night in seven healthy men (aged 26-33 yrs), both in resting condition and before and after a physical exercise performed between 10.40 and 11.00 p.m.. The exercise consisted in bicycling on a bicycle ergometer at 50% of the personal maximal work capacity (MWC) for 10 min, followed by other 10 min of bicycling at 80% of the MWC. The results clearly showed that physical stress at night significantly blunts the nocturnal increase in plasma melatonin levels (group X time interaction: p less than 0.00001; two-way ANOVA with repeated measures). These findings, taken together with the data of the literature, suggest that the response of the pineal gland to provocative stimuli may depend on its level of activity when the stimulus is applied.

Adult↗

PubMed1990

Nerve growth factor induces a dose-dependent and long-lasting increase of choline acetyltransferase activity in the septal area and hippocampus of uninjured rats.

The effect of nerve growth factor (NGF) on the intact septohippocampal cholinergic system of adult rats was studied. Nerve growth factor was continuously infused at different doses (5-100 micrograms) for two weeks into the lateral ventricle of adult rats. Controls received intracerebroventricular infusion of equal amounts of cytochrome c. Nerve growth factor treatment was capable of inducing a dose-dependent increase of choline acetyltransferase activity (ChAT) in septal area and ventral hippocampus. In both areas, the NGF-induced rise of ChAT activity was sustained for at least one week after infusion, then it progressively declined towards control values. By three and five weeks, using NGF at 25 and 100 micrograms respectively, ChAT increase was still significant in both septum and ventral hippocampus. The present findings corroborate a role for NGF in adult septohippocampal cholinergic system and indicate that the "pharmacological" modulation of these neurons by NGF may last several weeks following withdrawal of this trophic factor.

Animals↗

PubMed1990

Monosialoganglioside effects following cerebral ischemia: relationship with anti-neuronotoxic and pro-neuronotrophic effects.

Increasing evidence is available indicating that systemically administered GM1 is able to provide for functional recovery in different experimental models of CNS injury, including cerebral ischemia. Current evidence indicates that the GM1 effects are associated, in the acute phase, with attenuation of secondary neuronal damage due to its capability to antagonize excitatory amino acid-related neurotoxicity in vivo as in vitro. Furthermore, the ganglioside is able to facilitate occurrence of long-term reparative processes, an effect most likely reflecting the potentiation of the action of neuronotrophic factors. This bifaceted action of GM1 makes the ganglioside ideally suited for clinical treatment of patients afflicted by cerebrovascular insufficiencies.

Animals↗

PubMed1989

Nerve growth factor affects uninjured, adult rat septohippocampal cholinergic neurons.

The effect of nerve growth factor on the intact versus injured septohippocampal cholinergic system of adult rats was studied. Nerve growth factor was continuously infused into the lateral ventricle of adult uninjured rats or rats that had received unilateral partial transection of the fimbria. Controls (operated and unoperated) received intraventricular infusion of cytochrome c. After 2 weeks of nerve growth factor or cytochrome c treatments, choline acetyltransferase and acetylcholinesterase activities were measured in the septal area and in the hippocampus (divided into dorsal, medial and ventral parts). The continuous infusion of nerve growth factor resulted in a marked dose-dependent increase of choline acetyltransferase activity in both septum and hippocampus of adult unlesioned rats. In lesioned rats the nerve growth factor treatment was capable of inducing choline acetyltransferase activity in the hippocampus of not only the lesioned but also the unlesioned side, as well as in the septal area. In addition, nerve growth factor affected choline acetyltransferase activity differently in the hippocampus of the operated side with respect to the contralateral side or in unoperated animals. The chronic infusion of nerve growth factor did not affect acetylcholinesterase activity in the septum or in the hippocampus of either lesioned or unlesioned rats. The present findings indicate that nerve growth factor is capable of modulating the function of not only damaged but also normal adult forebrain cholinergic neurons. This suggests that nerve growth factor may modulate the function of these neurons in adulthood.

Acetylcholinesterase↗

PubMed1989

[Morphologic and hist-enzymatic aspects of palmar aponeurosis in a patient with Marfan syndrome associated with Dupuytren's contracture].

In this study we examined morphological and structural aspects of aponeurotic fragments from one patient with Dupuytren and Marfan diseases. Our purpose was to evaluate if characteristic features of Dupuytren aponeurosis are in some way influenced by alterations in collagenic and elastic bundles present in Marfan syndrome. So we compared histological, enzymatic and immunochemical features of tissue fragments from Marfan with similar fragments from simple Dupuytren patients. We observed a substantial difference in the predominant type of collagen which is adult type I in the normal Dupuytren disease and fetal type III in Marfan patient. Collagenic bundles are more dispersed in Marfan, and the whole aponeurosis seems less compact and resistant. No difference was observed in cellular populations of aponeurosis, and also myofibroblasts are present with abundant myosin ATPase activity both in Marfan with Dupuytren both in Dupuytren alone.

Collagen↗

PubMed1988

GM1 ganglioside potentiates the effect of nerve growth factor in preventing vinblastine-induced sympathectomy in newborn rats.

The effects of vinblastine (VNB) and nerve growth factor (NGF) administrations were assessed on sympathetic nerve terminals by measuring the noradrenaline (NA) content in the heart, spleen and kidneys of developing animals. Six-day-old rats, treated with 0.15 mg/kg VNB on postnatal day 3 (P3) showed a dramatic decrease of NA content in all these organs. This reduction was prevented by daily administrations of NGF on P3, P4 and P5. The effectiveness of NGF in inhibiting the VNB-induced sympathectomy was related to the dose administered and to the time interval between the VNB administration and the first NGF injection given on P3. Dose-response curves to NGF (ranging from 0.01 to 0.5 mg/kg) were obtained in both heart and spleen of VNB-treated animals. Thus, this experimental paradigm provides a quantitative assessment of the NGF activity in vivo. The systemic administration of GM1 (30 mg/kg) on P3, P4 and P5, was able to potentiate the NGF activity in preventing the VNB-induced sympathectomy. This GM1 effect was more evident in the heart and may be, at least in part, attributed to increased NGF prevention of neuronal cell death due to VNB. These results suggest an in vivo interaction between exogenous GM1 and NGF and are consistent with the view that neuronal cell repair related to in vivo administration of this ganglioside may rely on its capability to modulate the activity of endogenously occurring neuronotrophic factors.

Adrenergic Fibers↗

PubMed1988

General toxicity and peripheral nerve alterations induced by chronic vincristine treatment in the rabbit.

The effects of five 0.3 mg/kg intravenous administrations of vincristine (VCR) at weekly intervals were studied in the rabbit. Body weight gain was impaired starting from the first injection, while gross signs of motor paralysis and hair loss initiated from the third week. At the end of the observation period blood analysis revealed normocytic normochromic anemia, elevated serum creatine kinase, and low serum alkaline phosphatase, whereas all the tested parameters related to liver and kidney functions where within normal limits. The decreased number of red blood cells was the consequence of a complete, although reversible, blockade of staminal hematopoietic activity. Two important indexes of peripheral nerve function were clearly altered at the end of the treatment: (i) the sciatic nerve conduction velocity in vitro was 27% reduced and (ii) the latency between sciatic nerve stimulation and extensor digitorum longus (EDL) twitch in vivo was 34% prolonged. The usefulness of the rabbit as an animal model to study side-effects of VCR treatment is discussed.

Alkaline Phosphatase↗

PubMed1986

GM1 ganglioside counteracts selective neurotoxin-induced lesion of developing serotonin neurons in rat spinal cord.

The effect of exogenous monosialoganglioside GM1 on neurotoxin-induced lesioning of bulbo-spinal serotonergic neurons of newborn rats was studied by means of biochemical and immunocytochemical techniques. 5,7-dihydroxytryptamine (5,7-HT, a selective serotonin neurotoxin) treatment of newborn rats caused a pronounced reduction of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels in the thoracic and lumbar spinal cord, while an increase of 5-HT and 5-HIAA was found in the pons medulla. These biochemical alterations were regionally correlated with similar changes in 5-HT nerve terminal density analyzed by image analysis. GM1 administration (30 mg/kg for 4 consecutive days) antagonized the reduction of 5-HT and 5-HIAA levels induced by 5,7-HT treatment in the lumbar spinal cord of 2-month-old rats, as well as the decrease of 5-HT nerve terminal density in both thoracic and lumbar spinal cord of 1- and 2-month-old rats. A minor counteracting effect of GM1 was found in the pons medulla where the neurotoxin induced an increase of 5-HT and 5-HIAA levels. These data support the hypothesis that GM1 may have a preventing action on retrograde degenerative processes following chemical lesion and/or a growth-stimulating effect on injured 5-HT neurons.

5,7-Dihydroxytryptamine↗

PubMed1986

Influence of ACE inhibition on pulmonary haemodynamics and function in patients in whom beta-blockers are contraindicated.

The effects of captopril have been studied in 19 patients suffering from chronic obstructive pulmonary disease (COPD). In 9 of these patients with pulmonary hypertension (mean pulmonary artery pressure greater than 20 mm Hg), we studied the effects of the drug on pulmonary haemodynamics, blood gases and systemic circulation. Haemodynamic data were recorded before oral captopril 50 mg and for the next 60 minutes. Following captopril administration, significant reductions in mean pulmonary artery pressure (PAP) (P less than 0.05), in mean pulmonary wedge pressure (PWP) (P less than 0.05) and in total pulmonary resistance (TPR) were noted; significant reductions in mean brachial artery pressure (BAP) and systemic vascular resistance (SVR) were also recorded, while cardiac output, heart rate and blood gas tensions showed no significant changes. Furthermore, the higher the hypoxaemia was, the greater the reduction in BAP (P less than 0.05). In the other 10 COPD patients with moderate essential hypertension, captopril was given as monotherapy (75-10 mg/day) for 60 days. We found no significant modification of the various respiratory function tests except for an increase in the vital capacity (P less than 0.05). Systolic blood pressure and diastolic blood pressure were reduced both in the supine and in the standing position and there were no side effects, in particular no bronchospasm even in the patients responsive to bronchodilator drugs. Our data suggest that captopril is an effective and safe drug when administered to COPD patients with essential hypertension. Moreover, in these patients, it may protect the pulmonary circulation from hypoxic pulmonary vasoconstriction.

Adult↗