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Biomedical subjects

F Benfenati

Publications and source records attributed to F Benfenati.

At least 127 records · Page 7Linked to original sources

Gangliosides increase the survival of lesioned nigral dopamine neurons and favour the recovery of dopaminergic synaptic function in striatum of rats by collateral sprouting.

The effects of chronic ganglioside treatment GM-1 (10 mg/kg, i.p., once daily for 56 days) have been evaluated on the degenerative and regenerative features of nigrostriatal dopamine (DA) neurons following a partial lesion by tyrosine hydroxylase immunocytochemistry in combination with morphometrical analysis and by quantitative DA receptor autoradiography. Chronic GM-1 treatment resulted in the maintenance in the number of DA cell bodies, terminals and striatal area on the lesioned side and also increased dendrite length of the DA nerve cells in the zona reticulata on that side. The lesion induced DA receptor supersensitivity was counteracted by chronic treatment with GM-1 and the apomorphine induced rotational behaviour was significantly reduced. The hypothesis is introduced that following ganglioside treatment some lesioned DA nerve cells do not degenerate, but elongate their dendrites to give increased trophic support to DA cell bodies with intact DA axons. These increased dendro-dendritic interactions may enable the unlesioned DA cells to increase the density of their striatal nerve terminal networks via collateral sprouting leading to recovery of dopaminergic synaptic function as evidenced in the receptor autoradiographical and behavioural analysis. Gangliosides may therefore possibly represent a new type of drug in the treatment of Parkinson's disease and aging processes in DA systems.

Animals↗

Evidence for the existence of receptor--receptor interactions in the central nervous system. Studies on the regulation of monoamine receptors by neuropeptides.

Substance P (SP) (10(-8) M) can rapidly reduce the affinity and increase the density of 3H-5-HT binding sites in spinal cord membranes. CCK-8 and CCK-4 (10(-8) M) can rapidly and differentially change the characteristics of 3H-spiperone striatal binding sites linked to DA receptors of the D2 type. CCK-4 increase and CCK-8 reduce the number of striatal binding sites for 3H-spiperone, indicating for the first time separate CCK-4 binding sites. CCK-4 (10(-8) M) but not CCK-8 (10(-8) M) can rapidly reduce the affinity and increase the number of the 3H-spiperone binding sites linked to 5-HT receptors of the dorsal cerebral cortex of rats. CCK-8 (10(-8) M) only produces a trend for a small increase in the Bmax values of these receptors. These results again imply the existence of separate CCK-4 binding sites in this case in the cerebral cortex. Glutamate (10(-6) M), but not N-methyl-D-aspartate (10(-6) M) can rapidly change the characteristics of the 3H-N-propylnorapomorphine (3H-NPA) binding sites in striatal membranes of rats. Glutamate (10(-6) M) increases the density and especially reduces the affinity of the 3H-NPA binding sites, which label D2 and D3 types of DA receptors. Taken together the present findings give evidence that neuropeptide receptors and glutamate receptors can in vitro rapidly modulate the characteristics of different types of DA and 5-HT receptors by way of receptor--receptor interactions at the comodulate level or at the local circuit level. It is hypothesized that these receptor--receptor interactions are of importance for the encoding of short-term memory.

Animals↗

Effects of systemic and intracerebroventricular domperidone treatment on striatal and hypothalamic dopaminergic neurons.

In this study we compared the effects of systemic administration of haloperidol (HAL), a typical dopaminergic antagonist and of domperidone (DOM), a dopamine (DA) receptor blocker which does not cross the blood brain barrier but has a potency similar to HAL at DA receptors, on hypothalamic and striatal DA system turnover (evaluated by means of HVA and DOPAC levels) and prolactin (PRL) secretion in male rats. In accordance with previous data, we found that HAL (1 mg/kg, i.p.) raised DOPAC and HVA levels whereas DOM (1 mg/kg, i.p.) did not alter DA turnover in striatum. Both DOM and HAL affected the hypothalamic DA system, increasing DOPAC levels in a pattern similar to that observed in PRL secretion. An intracerebroventricular (icv) injection of DOM and HAL (4 micrograms/10 microliters/rat) was then made to investigate its effect on DA turnover in this experimental condition at striatal and hypothalamic level. DOM stimulated DA turnover a little in the striatum though its action was delayed; no effects were seen on HVA and DOPAC concentrations in the hypothalamus at any of the tested times. On the other hand, an equal amount of HAL induced an increase in striatal HVA and DOPAC levels, with no significant effects on hypothalamic DA metabolites. These results show that systematically administered DOM and HAL may affect the hypothalamic tuberoinfundibular DA system, probably acting through PRL release. Furthermore DOM, even when injected icv, shows only weak antidopaminergic action on DA turnover in both central areas.

3,4-Dihydroxyphenylacetic Acid↗

A new approach to quantitate the density and antigen contents of high densities of transmitter-identified terminals. Immunocytochemical studies on different types of tyrosine hydroxylase immunoreactive nerve terminals in nucleus caudatus putamen of the rat.

By means of a semi-automatic image analyzer plugged into an Apple II computer and suitable computer programs it is possible to analyze transmitter-identified nerve terminals. Thus, a densitometric approach is applied on the original photograph followed by systematic sampling which is carried out by means of a grating of circles. This procedure allows the study quantitatively of density and intensities of different types of densely packed tyrosine hydroxylase (TH) immunoreactive nerve terminals of the nuc. caudatus putamen. It is shown that the islandic TH immunoreactive nerve terminals have a higher density, but a TH content similar to the diffuse types of TH immunoreactive nerve terminals in the nuc. caudatus putamen.

Animals↗

Selective reduction of adrenaline turnover in the dorsal midline area of the caudal medulla oblongata and increase of hypothalamic adrenaline levels in the Lyon strain of genetically hypertensive rats.

Catecholamine levels and turnover have been studied in 5 week old male genetically hypertensive (LH) and normotensive (LN) rats of the Sprague-Dawley Lyon strain. The results demonstrate increased hypothalamic adrenaline levels and a reduced adrenaline turnover in the dorsal midline of the medulla oblongata (DCMO) in the LH rats compared with LN control rats. The reduction of adrenaline turnover in the DCMO may contribute to the development of spontaneous hypertension.

Animals↗

Principles for the morphological characterization of transmitter-identified nerve cell groups.

Principles for a morphometric description of transmitter identified nerve cell groups have been introduced, exemplified on the 5-HT nerve cell group of nucleus raphe dorsalis (B7 cell group), using immunocytochemical procedures to visualize 5-HT. Both cell body parameters (mean diameter, mean perimeter, mean area, shape factor) and cell group parameters (number of cells, mean free distance among cells, volume fraction, gravity centre, major axis slope with respect to the midline) have been considered. These parameters have been obtained by the use of a semiautomatic image analyzer (Kontron MOP AMO2) plugged into an Apple II computer. By the use of this system and of suitable computer programs, it is possible to give a Cartesian representation of 5-HT nerve cell bodies in a coronal section under study. The present work has mainly one aim. To detect whether subgroups exist within a transmitter-identified cell group. Two approaches have been introduced to obtain, on objective grounds, evidence whether or not a group consists of subgroups. The first of these approaches is based on differences in cell body density within the cell group, while the second approach is based on frequency distribution analysis. This second approach is mainly sensitive to shape changes of the cell group.

Animals↗

Neuroanatomical methods for the quantitative evaluation of coexistence of transmitters in nerve cells. Analysis of the ACTH- and beta-endorphin immunoreactive nerve cell bodies of the mediobasal hypothalamus of the rat.

A new statistical approach has been introduced to study in a quantitative way the coexistence of two neuromodulators in nerve cell bodies. The method has been exemplified on the ACTH-like and beta-endorphin-like immunoreactive nerve cell bodies of the mediobasal hypothalamus demonstrated by means of indirect immunofluorescence methodology. The method is based on the analysis of 3 adjacent sections which, in a random way, are stained with antiserum against neuromodulator 1, against neuromodulator 2 and with antisera against both neuromodulator 1 and neuromodulator 2. It could be shown that some neurons of the mediobasal hypothalamus do not contain at a detectable level both ACTH- and beta-endorphin-like immunoreactivity. The present method also involves an analysis of the two nerve cell groups by means of a morphometric procedure to collect additional information on the extent of coexistence. Thus, by this approach the gravity centers of the two cell groups can be calculated. The distances between the two gravity centers of the ACTH and beta-endorphin positive cell groups were significantly different at certain levels. The present method offers unique possibilities in increasing our understanding of the functional significance of coexistence of neuromodulators in one and the same nerve cell body since it makes possible a quantitative evaluation of coexistence. The usefulness of the present method is illustrated by the findings of a possible differential synthesis of ACTH- and beta-endorphin-like material in certain cell bodies of the mediobasal hypothalamus.

Adrenocorticotropic Hormone↗

Gastric inhibitory polypeptide release after oral glucose: relationship to glucose intolerance, diabetes mellitus, and obesity.

Hypersecretion of immunoreactive gastric inhibitory polypeptide (IRGIP) has been reported previously in patients with diabetes mellitus (DM) and obesity. To ascertain the relative contribution of glucose intolerance and obesity to the abnormalities of IRGIP secretion, 114 subjects were studied during a standard oral glucose (75 g) tolerance test; responses of glucose, insulin, C-peptide, IRGIP, and glucagon were evaluated. The subjects were divided into six subgroups according to body weight and the degree of glucose intolerance. In normal weight subjects, the IRGIP response to oral glucose was significantly higher in the patients with impaired glucose tolerance (IGT) and DM than in the healthy control subjects (P less than 0.05). In the obese subjects, no significant differences in mean IRGIP responses could be detected among control, IGT, and DM subjects. In spite of similar IRGIP responses, the obese IGT patients did release more insulin than the obese control subjects, suggesting that incretin factors other than GIP may be operative in this condition. When obese and nonobese patients were compared, the obese subjects with normal glucose tolerance released a greater amount of IRGIP and insulin than the normal weight controls, whereas no significant difference between obese and nonobese could be found within the IGT and DM groups. We conclude that in the absence of obesity, glucose intolerance may induce IRGIP hypersecretion. On the other hand, obesity is associated with IRGIP hypersecretion, and glucose intolerance has no further effect, indicating a different pathogenetic mechanism for the IRGIP abnormalities. In both the obese and nonobese diabetic groups, IRGIP hypersecretion was associated with a failure of plasma glucagon levels to fall after oral glucose; this effect might be related to the glucagonotropic action of this peptide.

Adult↗

Possible mixed agonist--antagonist activity of D-sulpiride at dopamine receptor level in man.

The effects of different doses of D-sulpiride (1, 6, 12 and 25 mg, i.v.) on arterial blood pressure (ABP), heart rate (HR) and prolactin (PRL), growth hormone (GH), insulin and gastrin secretions have been studied in 8 normal men. D-Sulpiride increased systolic ABP with a maximum effect rather 12 mg i.v., while it had only slight effects on diastolic ABP and HR. PRL secretion was increased by D-sulpiride in a dose-dependent way, while insulin secretion was lowered and GH secretion slightly enhanced only in a restricted range of doses (6 mg and 12 mg i.v., respectively). Gastrin secretion seemed to be unaffected by D-sulpiride at any of the tested doses. These results are discussed in view of a possible mixed agonist--antagonist activity of D-sulpiride at dopamine receptor level in contrast with the relatively pure antagonistic action of the levo isomer.

Adult↗

Effects of the interaction between methysergide and clonidine on growth hormone and prolactin secretion in normal man.

The effects of methysergide (1 mg, p.o.), clonidine (50 micrograms, i.m.) and methysergide plus clonidine on growth hormone (GH) and prolactin (PRL) secretion in 8 normal male volunteers have been studied. Both methysergide and clonidine were found to enhance GH and to lower PRL plasma levels. The effects of methysergide are explained on the basis of a preferential action of methysergide metabolites on dopamine receptors, whereas the effects of clonidine are attributed to a stimulatory action on adrenaline receptors. The combined treatment methysergide plus clonidine resulted in a potentiation of the effects caused by the drugs when administered alone.

Adult↗

Abnormal control of growth hormone secretion by opiate systems in acromegalic patients: a study with naloxone and 2-Br-alpha-ergocryptine (CB 154).

The present study was undertaken with the aim of exploring the role that opiate systems may have in neuroendocrine control in acromegaly. The effects of naloxone (0.4 mg, i.m.), of 2-Br-alpha-ergocryptine (CB154, 2.5 mg, p.o.) and of the interaction between CB154 and naloxone on growth hormone (GH) and prolactin (PRL) secretion were studied in 11 acromegalic patients. CB154 reduced both GH and PRL serum levels, naloxone only GH serum levels. The latter effect deserves further study aimed at a possible new therapeutic approach to GH hypersecretion observed in acromegaly. Naloxone also interfered with the lowering effects of CB154 and GH and PRL serum levels, pointing to the existence of an interaction between dopaminergic and opiate control of GH and PRL secretion in acromegaly.

Acromegaly↗

A new hypothesis on memory - a possible role of local circuits in the formation of the memory trace.

An hypothesis is proposed arguing that local circuits might work as biochemical units involved in synthesis of macromolecules related to the memory processes. Specific sequences in the activation of local circuits should act as a "template" for the synthesis of particular memory molecules, which, in turn, may facilitate the repetition of the original sequences of bioelectrical signals (short-term memory). The resynthesis of the local memory molecules in cell body areas, their flow to terminal areas via axoplasmic transport and their possible passage to other nerve cells via transynaptic transport might be the basis of long term memory. The role of diffuse neuronal systems (e.g. noradrenaline systems) is discussed in the frame of memory recall and consolidation. The suggested hypothesis can be represented in a very effective way by means of the graph theory.

Animals↗

[Small guillotine to obtain reproducible coronal sections from rat brain].

In order to study the morphology and function of central catecholaminergic and peptidergic neurons, it is necessary to obtain reproducible brain sections from several animals. We describe here a cutting machine for sectioning unfixed brains in frontal planes. This versatile guillotine gives a high degree of repeatability in sectioning brains of different animals in defined frontal planes.

Animals↗

[Effects of sulpiride isomers in the control of blood pressure in man].

The effects of d-Sulpiride (25 mg i.v.) and 1-Sulpiride (25 mg i.v.) administration in the control of arterial blood pressure (ABP) and PRL-GH secretion have been analyzed in five normal male volunteers. It was observed a quite different action on ABP, 1-Sulpiride causing a long lasting hypotension and d-Sulpiride a short-lived hypertension. The correlation between ABP, heart rate and PRL-GH levels suggests a probable central cation for 1-Sulpiride and a possible peripheral action for d-Sulpiride effects on ABP.

Blood Pressure↗