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Biomedical subjects

A Gorio

Publications and source records attributed to A Gorio.

At least 55 records · Page 3Linked to original sources
PubMed1992

Intraspinal degenerative atrophy caused by sciatic nerve lesions prevented by acetyl-L-carnitine.

Peripheral nerve lesions cause retrograde changes in the spinal cord, involving initially the descending serotoninergic pathways and later the substance P sensory input and methionine-enkephalin interneurons. Within 48 h after sciatic nerve resection there is a significant increase of 5-hydroxyindoleacetic acid in the lumbar spinal cord with no changes of serotonin metabolism in the cell body areas. The immunocytochemical analysis of the spinal cord shows that 20 days after nerve lesion there is a loss of substance P-positive boutons in the laminae I and II of the dorsal horn in the lumbar segment. Such a morphological change is correlated by radioimmunoassay for substance P and methionine-enkephalin, that reveals a significant loss of both peptides. Treatment with acetyl-L-carnitine prevents the early 5-hydroxyindoleacetic acid increase and the reduction of peptide content observed 20 days after lesioning the sciatic nerve. These data suggest that treatment with acetyl-L-carnitine exerts a neuroprotective activity preventing the retrograde changes triggered by peripheral nerve lesions.

Acetylcarnitine↗
PubMed1992

Role of endothelin-1 in carrageenin-induced inflammation.

Many vasal factors are produced during an experimental model of inflammation such as rat-paw oedema induced by carrageenin. We investigated whether among the other well-known mediators of inflammation, i.e. serotonin, PAF, eicosanoids and kinins, the peptide endothelin-1 is produced by this kind of inflammatory process caused by carrageenin. Our results indicated that plasma endothelin, and the tissue concentration of endothelin in the oedematous paw, is increased as compared to the control. Consequently, endothelin should also be considered as an important factor in inflammatory processes.

Animals↗
PubMed1992

Counteraction on experimentally induced diabetic neuropathy by levocarnitine acetyl.

The effect of levocarnitine acetyl on diabetic peripheral neuropathy induced by a single injection of streptozotocin or alloxan was studied. Levocarnitine acetyl was administered intraperitoneally one week after induction of diabetes at the dose of 50 mg/kg/day for five and ten weeks. At the end of treatment, neuromuscular conduction velocity (m/sec) was evaluated by stimulating the sciatic nerve and recording the soleus muscle potentials evoked, and the muscle contraction force (mm) by measuring the isometric muscular tension. Motor coordination was evaluated on the Rota-rod apparatus. Treatment with levocarnitine acetyl fully prevented the reduction (20%) in the neuromuscular conduction velocity observed in both experimental models of diabetes. The decrease (30-33%) in muscle contraction force was prevented partially in streptozotocin-induced diabetes and fully in alloxan-induced diabetes. Levocarnitine acetyl also improved the concomitantly reduced motor performance. The results of the present study suggest a beneficial effect of levocarnitine acetyl on peripheral neuropathy and muscle performance.

Acetylcarnitine↗
PubMed1992

Perinatal exposure to ethanol affects postnatal degeneration and regeneration of serotoninergic pathways in the spinal cord.

It has been reported that chronic ethanol exposure during intrauterine life may cause severe adverse effects in early infancy that have been termed fetal alcohol syndrome. These alterations may perturb the normal brain development as though alcohol exposure might have altered the basic cellular interrelationship underlying neuronal plasticity. The neonatal lesion of the serotoninergic pathways in the central nervous system with the selective neurotoxin 5,7-DHT supplies an ideal model for studying the effects of substances of abuse on degenerative and regenerative events. The authors' data indicate that perinatal exposure to ethanol (3% in drinking water) causes a more rapid degeneration of the serotoninergic pathways affected by 5,7-DHT; conversely, regeneration and reinnervation of the lumbar spinal cord are markedly improved by ethanol exposure. These results suggest that perinatal ethanol exposure promotes cellular changes that at later stages are capable of improving neural repair in the brain.

5,7-Dihydroxytryptamine↗
PubMed1991

Early alterations of Gi/Go protein-dependent transductional processes in the retina of diabetic animals.

The early alterations of G-protein-dependent transductional mechanisms have been characterized in the retina of alloxan-treated diabetic rats. Five weeks after alloxan injection, pertussis toxin radiolabeling of Gi/Go proteins was markedly reduced in the retina of diabetic animals, suggesting either a reduced expression and/or the presence of some structural modification of these G-protein subtypes. The functional activity of Gs proteins, measured as stimulation of membrane adenylate cyclase by dopamine, did not seem to be impaired at this stage of the pathology; basal adenylate cyclase activity was indeed increased in diabetic rats, consistent with the observed reduction of Gi/Go inhibitory proteins. Such functional alterations of the cAMP producing system were causally related to diabetes induction, since they were reversed by treatment of diabetic animals with insulin. These results suggest that G-protein dependent transduction mechanisms are altered in the retina of diabetic animals, and that a defect of Gi/Go proteins could represent an early transductional damage in the development of diabetic retinopathy.

Adenylyl Cyclases↗
PubMed1989

Reversibility and prevention of intraspinal peptidergic loss caused by sciatic nerve lesions.

We have investigated the reversibility and prevention of peptidergic losses in the lumbar spinal cord caused by permanent resection of sciatic nerve. The lesion triggers a series of degenerative events involving the substance P sensory imput as well as met-enkephalin interneurons of the substantia gelatinosa. The degenerative processes are evident 10 days after sciatic nerve lesion and are gradually reversible as shown by radioimmunoassay and quantitative immunocytochemistry. Recovery begins 30 days postlesioning and full restoration is observed at 90 days. Serotonin (5-HT) turnover is markedly affected by sciatic nerve lesion as soon as 24 hr postlesioning, when 5-HT metabolism is enhanced, returning to control levels just preceding the peptide alterations; 5-HT metabolism then undergoes a transient period of hypoactivity which correlates with the beginning of the peptidergic restorative processes. Altogether these results, with previous observations showing that 5-HT depletion prevents metenkephalin interneurons degeneration triggered by the lesion (Di Giulio et al.: J Neurosci Res 18:443-448, 1987), suggest a role for 5-HT in the synaptic plasticity of the substantia gelatinosa of the spinal cord. The administration of gangliosides (10 or 50 mg/kg) to sciatic-nerve-lesioned animals fully prevented the metenkephalinergic degeneration without affecting the degenerative atrophy of the lesioned substance P sensory imput.

Animals↗
PubMed1989

Denervation and hyperinnervation in the nervous system of diabetic animals. I. The autonomic neuronal dystrophy of the gut.

Peripheral neuropathy is a correlate of experimental diabetes induced in rats by means of a single injection of alloxan. The autonomic and enteric innervation of the gut are profoundly affected in the small intestine of such animals. A complex process of denervation and hyperinnervation of the gut wall of diabetic animals is observed. It was previously reported that the cholinergic parasympathetic innervation of the intestine is markedly reduced. We have found that noradrenergic sympathetic axons hyperinnervate the duodenum of diabetic rats, whereas noradrenaline levels are significantly reduced in the jejunum. The putative enteric neurotransmitter dopamine is also present in higher levels in the duodenum. The intrinsic peptidergic neurons of the gut are deeply affected as well in diabetic rats. Substance P and met-enkephalin content are remarkably reduced throughout the small intestine, whereas vasoactive intestinal polypeptide levels (VIP) are significantly increased in the duodenum. Indeed, immunocytochemical staining of the ileum did reveal hypertrophy of VIP-positive axons in diabetic rats. The intrinsic serotoninergic innervation of the gut is apparently unaffected. Our results indicate that the changes of gut innervation observed in experimental diabetes are consistent with increased content and also likely with hyperinnervation by the neuronal systems involved in smooth muscle relaxation and decreased content and with denervation by those systems with smooth muscle contraction properties. Such a perturbed gut innervation may be responsible of the gastrointestinal dysfunctions that are among the most common complications of diabetes.

Alloxan↗
PubMed1989

Denervation and hyperinnervation in the nervous system of diabetic animals. II. Monoaminergic and peptidergic alterations in the diabetic encephalopathy.

The monoaminergic innervation of the central nervous system (CNS) is characterized by long and short projecting neurons. The neurological correlates of diabetes are usually referred to as processes of degenerative atrophy affecting motor and sensory peripheral nerves. We have found that the long serotoninergic axons innervating the spinal cord and the cerebral cortex are unaffected in diabetic animals and that the noradrenergic innervation of the cortex is normal as well. The serotonin content is doubled in the hypothalamus with no apparent alteration of 5-HIAA levels, suggesting a supernumerary innervation that is accompanied by a reduced release. In pons medulla oblongata, serotonin and dopamine with the relative metabolites 5-HIAA and DOPAC are significantly reduced, whereas noradrenaline is markedly increased. In the hippocampus, there is a reduction of serotonin content. The serotoninergic alterations are peculiar as suggested by the sparing of the most distal projections that is accompanied by hyperinnervation of the hypothalamus and the loss of shorter collaterals in the pons medulla oblongata. In the hypothalamus and in the striatum of diabetic rats, there are significant higher levels of substance P and met-enkephalin, respectively. The abundance of proenkephalin A mRNA is also increased in the striatum. Conversely, in the lumbar cord of diabetic animals, the levels of substance P and met-enkephalin are significantly reduced. Such alterations likely reflect retrograde degeneration of the peripheral sensory input. The CNS changes are unlikely due to vascular abnormalities in the brain of diabetic rats; rather, we suggest that the persistent lack of insulin is the major factor involved as a trigger of the monoaminergic changes in the diabetic brain.

Animals↗
PubMed1989

Denervation and hyperinnervation in the nervous system of diabetic animals: III. Functional alterations of G proteins in diabetic encephalopathy.

G protein-mediated effects on cAMP production were evaluated in the corpus striatum of diabetic rats 5 and 14 weeks after alloxan injection by measuring both D1-receptor-induced stimulation and D2-receptor-mediated inhibition of adenylate-cyclase activity. At 5 weeks of diabetes, no obvious alterations of G protein functions were detected. Both dopamine-stimulated adenylate cyclase and bromocriptine-induced inhibition of enzyme activity were indeed similar in control and diabetic animals. Fourteen weeks after alloxan injection, profound alterations were observed. Dopamine-stimulated cAMP production was markedly increased in diabetic rats, whereas bromocriptine ability to reduce cAMP formation was almost abolished at this late stage of diabetes. Hypoactivity of Gi/Go proteins was also confirmed by the reduced ability of the GTP non-hydrolyzable analog GTP-gamma-S to inhibit forskolin-stimulation of adenylate cyclase. These results show an apparent functional imbalance between Gs and Gi/Go-mediated transduction mechanisms, with an increased efficacy of Gs activity likely due to the loss of Gi/Go inhibitory functions. Concomitantly with such transductional alteration detected in chronic diabetes, we observed a marked increase of the striatal content of met-enkephalin, which is known to utilize Gi/Go proteins for inhibition of adenylate cyclase. The measurement of other transmitters (vaso-active intestinal peptide, substance P, serotonin, noradrenaline, and dopamine) did not reveal any difference with respect to controls. The observed transductional defect in diabetic animals and the increased content and/or hyperinnervation by the metenkephalinergic system could be correlated as mutual compensatory mechanisms.

Adenylyl Cyclases↗
PubMed1988

Modified ontogenesis of enkephalin and substance P containing neurons after perinatal exposure to morphine.

The development of met-enkephalin (ME) and substance P (SP) neurons has been studied in rats exposed to morphine during the perinatal period up to day 30 of life. Both peptides levels were measured by specific radioimmunoassays. ME developmental pattern is markedly affected by morphine in the pons-medulla oblongata, while SP does not seem to be influenced. It is suggested that the well known inhibitory effects of opiates on brain growth and maturation might take place by altering the developmental pattern of the endogenous opioid system.

Animals↗
PubMed1988

The synaptic vesicle proteins synapsin I and synaptophysin (protein P38) are concentrated both in efferent and afferent nerve endings of the skeletal muscle.

Synapsin I and synaptophysin (protein p38) are 2 major protein components of the membranes of small synaptic vesicles of virtually all presynaptic nerve endings. Synapsin I, a phosphoprotein regulated by both Ca2+ and cAMP, is a peripheral protein of the cytoplasmic surface of the vesicle membrane. It is thought to anchor the vesicle surface to the cytoskeleton of the terminal and to play a regulatory role in neurotransmitter release. Synaptophysin is an intrinsic transmembrane glycoprotein. We report here that both proteins are present and concentrated also in afferent nerve endings, which provide the sensory innervation of the skeletal muscle and of the tendon. The distribution of both antigens in sensory nerve endings is consistent with their localization on the microvesicles that have been described in such endings. Thus, our results suggest the existence of important biochemical, and possibly functional, similarities between small synaptic vesicles of presynaptic nerve endings and microvesicles of sensory endings. Such findings provide new clues to the understanding of the physiology of sensory endings.

Afferent Pathways↗
PubMed1987

Spinal cord interneuron degenerative atrophy caused by peripheral nerve lesions is prevented by serotonin depletion.

Peripheral nerve section causes a degenerative atrophy of substance P sensory input and of met-enkephalin interneurons in the dorsal horn of the spinal cord. Radioimmunoassay of both peptides indicates that the decrease in peptide levels ranges from 30 to 50%, that it occurs several days after lesioning, and that it is simultaneous for the two peptides. Quantitative immunocytochemistry performed by computer-assisted analysis of met-enkephalin-positive boutons shows that following sciatic nerve lesions there is a decreased density of immunoreactive boutons per unit area in the substantia gelatinosa of the dorsal horn in the lumbar cord ipsilateral to the lesion. Within 24 h of nerve injury there is a significant and transient enhancement of serotonin turnover, as indicated by the increased levels of 5-hydroxyindolacetic acid in the lumbar cord, without any change in serotonin concentrations. The restoration of normal serotonin metabolism at d 10 postlesioning coincides with the peptidergic loss. However, if, prior to nerve resection, serotonin stores are depleted by p-chlorophenylalanine treatment, the damage to met-enkephalin interneurons is fully prevented, while substance P loss does still occur. These results suggest that signals caused by the section of a peripheral nerve are directly responsible for substance P loss in the spinal cord and are, presumably, rapidly transported into the CNS, causing an activation of the serotoninergic raphe neurons projecting to spinal cord. The activation of this system is likely responsible for the degenerative atrophy of the met-enkephalin interneurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

A developmentally regulated isoform of 150,000 molecular weight neurofilament protein specifically expressed in autonomic and small sensory neurons.

Neurofilament heterogeneity has been demonstrated using a monoclonal antibody (CH1) specific for the 150,000 molecular weight neurofilament subunit. In the peripheral nervous system of adult rats CH1 stained selectively sympathetic and parasympathetic neurons and a subpopulation of small neurons in the sensory dorsal root ganglia. Somatic motor neurons and large neurons in dorsal root ganglia were completely unreactive. In contrast, the anti-neurofilament antibody iC8, directed against the 150,000 molecular weight subunit, labelled all peripheral nervous system neurons. The immunostaining pattern with both antibodies was unchanged by phosphatase treatment. These data indicate that two antigenically distinct variants of the 150,000 molecular weight neurofilament subunit exist in somatic and autonomic neurons of adult animals. In addition, the phosphatase treatment suggests that the antigen recognized by CH1 is not masked by phosphorylation. In contrast, all neurons were labelled by this antibody in the peripheral nervous system of newborn rats. It is suggested that CH1 identifies a fetal 150,000 molecular weight neurofilament polypeptide isoform whose expression is prevented by the growth of somatic neurons and is selectively maintained in autonomic and small sensory neurons.

Adrenergic Fibers↗