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Biomedical subjects

F Benfenati

Publications and source records attributed to F Benfenati.

At least 109 records · Page 6Linked to original sources
PubMed1986

Receptor autoradiographical evidence for high densities of 125I-neuropeptide Y binding sites in the nucleus tractus solitarius of the normal male rat.

By means of quantitative receptor autoradiography using 125I-neuropeptide Y (125I-NPY) as a radioligand, the distribution of 125I-NPY binding sites has been evaluated in coronal sections at various rostrocaudal levels of the medulla oblongata of the male rat. High densities of neuropeptide Y (NPY) binding sites were demonstrated in the nucleus tractus solitarius (nTS), in the nucleus paratrigeminalis, in the area postrema, in the medial nuclei of the inferior olive and in the substantia gelatinosa of the caudal part of the spinal trigeminal nucleus. Low densities were present in the dorsal motor nucleus of the vagus (dmnX) and in the hypoglossal nucleus. Other regions of the medulla oblongata showed only a very low density or no specific binding of 125I-NPY. These results indicate that the central cardiovascular actions of NPY at least in part may be mediated via an action in the nTS, in this way controlling the baroreceptor reflex activity. Neuropeptide Y mechanisms may also play a role in the regulation of other visceral afferents such as those involved in gastrointestinal control (dmnX) and of cerebellar function (inferior olive). Finally, the results indicate that a high density of NPY immunoreactive terminals in some regions of the medulla oblongata is associated with a low density of high affinity 125I-neuropeptide Y binding sites and vice versa.

Animals↗
PubMed1985

Effects of ganglioside GM1 treatment on striatal glucose metabolism, blood flow, and protein phosphorylation of the rat.

Effects of ganglioside GM1 administration have been studied in unilaterally partially hemitransected rats on striatal energy metabolism, using the radioactive deoxyglucose (DG) technique, on striatal blood flow, using radiolabelled iodoantipyrine (IAP) as tracer, and on cyclic AMP (cAMP) and Ca2+ induced protein phosphorylation in striatal membranes (P2 fraction). Ganglioside GM1 treatment counteracted the imbalance in striatal energy metabolism, in striatal blood flow, as well as in protein phosphorylation found between the striata of the lesioned and unlesioned side, possibly due to excitatory effects on the lesioned side and inhibitory effects on the unlesioned side. In intact animals, GM1 treatment produced a reduction in cAMP and Ca2+ induced striatal protein phosphorylation. Facilitatory actions of the ganglioside GM1 dominate following a lesion, probably due to its possible function as a modulator of receptors for neuronotrophic factors, leading to restoration of metabolic rate and of cAMP and Ca2+ induced protein phosphorylation in the striatum of the lesioned side. The results emphasize that ganglioside GM1 treatment can restore the metabolism of a partially innervated striatum towards normal, as evaluated both at the level of the entire striatal structure by means of the DG and IAP techniques and at the molecular level by means of studies on the cAMP and Ca2+ induced protein phosphorylation.

Animals↗
PubMed1985

Evidence for cholecystokinin-dopamine receptor interactions in the central nervous system of the adult and old rat. Studies on their functional meaning.

Evidence has been presented for the existence of interactions between CCK and DA receptors both in striatal and limbic membranes. A similar type of modulation by CCK-8 of DA receptors also exists after chronic neuroleptic treatment indicating that supersensitive DA receptors are also modulated by this peptide. As seen from simulation curves, CCK-8 increases the binding of [3H]DA agonists and reduces the binding of [3H]DA antagonists in striatal membranes, suggesting that CCK-8 may increase striatal DA transmission. Results of this type may underlie some of the non-neuroleptic effects of CCK-8. In the aged brain, the ability of CCK-8 to modulate DA antagonist binding sites is changed such that the binding of [3H]DA antagonists is increased. Thus, in the aged brain, receptor-receptor interactions may be altered, leading to a derangement of heterostatic mechanisms (mechanisms changing chemical transmission without interfering with synaptic homeostasis). It was also demonstrated that during aging there is a preferential disappearance of CCK-like immunoreactivity versus TH immunoreactivity in the nigral DA neurons, especially in the medially located nigral DA cells; furthermore, co-existence in the TH/CCK co-storing terminals in the nucleus accumbens was reduced during aging. Such alterations should also lead to changes in heterostatic regulation because the CCK co-modulation line controlling the DA receptors may be preferentially affected.

Aging↗
PubMed1984

Biochemical effects of minaprine on striatal dopaminergic neurons in rats.

The biochemical effects of minaprine, a new psychotropic drug, were investigated on striatal dopaminergic neurons in the rat. Minaprine did not displace [3H]spiperone in-vitro binding from striatal membranes but had clear effects on dopamine (DA) metabolites. Homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC) were significantly decreased in a dose-dependent manner after intraperitoneal administration of minaprine 30 min before killing. In rats injected with minaprine 15 mg kg-1 i.p. at different intervals, the decrease in striatal HVA and DOPAC was time-dependent and a concomitant rise in 3-methoxytyramine (3-MT) concentrations was observed. The maximum of these effects was reached 30 min after minaprine. When administered 5 min after a monoamineoxidase (MAO) inhibitor (pargyline, 100 mg kg-1 i.p.) and 30 min before killing, minaprine did not affect pargyline-induced changes in HVA, DOPAC and 3-MT levels. This together with other data suggests that minaprine affects DA metabolism by acting, at least partially, at presynaptic level through in-vivo inhibition of MAO activity.

Animals↗
PubMed1984

Studies on aging processes.

By means of computer assisted morphometry and microdensitometry it has been possible to characterize aging processes in transmitter identified neurons demonstrated at the presynaptic level by immunocytochemistry and at the postsynaptic level by receptor autoradiography. Three-month- and 24-month-old rats were used in the present study. It was discovered that the DA neurons innervating the striatum and nucleus accumbens underwent degeneration in the aging brain both at the pre- and post-synaptic level, while the DA synapses within the tuberculum olfactorium remained intact. In this quantitative receptor autoradiographical analysis 3H-spiperone and 3H-N-propyl-norapomorphine were used as radioligands for DA receptors. In comparison with the aging induced changes in DA receptors in the striatum and in the nucleus accumbens the alpha 2- and the beta-adrenergic receptors appeared to be more resistant to the aging process. In the analysis of the opiate receptors of the aging brain it could be demonstrated by quantitative receptor autoradiography using both radioligands for the mu-type (3H-etorphin) and delta-type (3H-d-ala2-d-leu5-enkephalin) of opiate receptors that there is a marked and widespread disappearance of both types of opiate receptors in the aging brain. It must be emphasized that no correlation exists in the degeneration pattern of the mu- and delta-type of opioid receptors indicating that they may represent two separate entities with separate trophic regulation. In contrast, it was discovered in the quantitative receptor autoradiographical analysis that 3H-flunitrazepam binding was increased in many areas of the aging brain compared with the adult rat brain. These results underline the heterogeneity in the degenerative patterns which take place in transmitter receptors in relation to aging. Thus, these results indicate that the simple replacement therapy in aged patients may not give optimal results. As a matter of fact, such treatments can lead to a further unbalance between the various types of transmitter identified neurons building up the neuronal networks of the brain, which are undergoing degeneration.

Aging↗
PubMed1984

Computer-assisted morphometry and microdensitometry of transmitter- identified neurons with special reference to the mesostriatal dopamine pathway. Methodological aspects.

New morphometrical and microdensitometrical approaches for evaluation of transmitter-identified neurons in the central nervous system have been developed. These rely at the presynaptic level on the use of immunocytochemistry and at the postsynaptic level on the use of receptor autoradiography. The immunocytochemical analysis involves the indirect immunofluorescence method and the indirect immunoperoxidase method utilizing cryostat and vibratome sections, respectively. In the postsynaptic analysis cryostat sections and tritium-sensitive film were employed. A block diagram representation of the system of the image analyzer used and its connection with its host computer is given. Furthermore, flow charts of the original software developed by our group in presented. The morphometrical analysis has been performed on coronal sections of rat brain resulting in determinations of cell body and cell group parameters. Based on this information, objective criteria have been introduced to assess the existence of a cell group of transmitter-identified neurons in a three-dimensional frame and to give a morphometrical description of this group in the space. Moreover, new quantitative approaches to describe the dendritic and terminal fields have been introduced and for the first time in this type of morphometrical analysis, the Lorenz curves and the Gini index have been utilized in the description of the pattern of dendritic and terminal networks. By means of these morphometrical approaches it became possible to analyze topological and biochemical heterogeneities within cell groups defined in the rostrocaudal frame. In particular, it has been possible to develop a quantitative method for the evaluation of coexistence in nerve cell bodies. This method has been called the overlap method and allows an analysis cell by cell of the possible coexistence of two or more antigens.

Animals↗
PubMed1983

Evidence for the existence of a dopamine receptor of the D-1 type in the rat median eminence.

By means of receptor autoradiography using the dopamine (DA) receptor radioligands [3H]cis(z)-flupenthixol ([3H]FLU), [3H]spiperone, [3H]N-propyl-norapomorphine and amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphtalene-2-(5,8[3H]) in combination with a microdensitometrical analysis indications have been obtained for the existence of a DA receptor of the D-1 type in the median eminence of the male rat. Thus, only [3H]FLU (10-20 nM) strongly labeled both the nuc. caudatus putamen and the median eminence and the labeling was markedly prevented by (+)-butaclamol in both regions. Furthermore, a DA receptor agonist of the D-1 type preferentially displaced [3H]FLU from the median eminence. Thus, a DA receptor of the low affinity type may regulate the secretion of hypothalamic hormones from the median eminence.

Animals↗
PubMed1983

Chronic ganglioside treatment counteracts the biochemical signs of dopamine receptor supersensitivity induced by chronic haloperidol treatment.

Chronic ganglioside treatment (10 mg/kg, i.p.) using the molecular species with only one neuroaminic acid residue (GM1) given together with haloperidol (0.3 and 5 mg/kg, i.p.) once daily in male rats, counteracted the haloperidol-induced increase in the number of [3H]spiperone binding sites in striatal membranes when the low dose of haloperidol, but not the high dose, was administered. The present results therefore indicate that chronic GM1 treatment can partially counteract the increase in the number of dopamine receptors having a high affinity for neuroleptics (D2 type) induced by chronic haloperidol treatment in striatal membranes, and therefore may also partially counteract the development of neuroleptic-induced dopamine receptor supersensitivity.

Animals↗
PubMed1983

A simplified method to determine binding parameters in a two-site case using linear regression.

A program using a simplified method to compute estimates of binding parameters in a system with two independent classes of binding sites is presented. An iterative method is used to approximate step-by-step the two lines describing the binding activities separately, starting from a curvilinear Scatchard or Hofstee plot. This method is designed for use on microcomputers with graphic facilities and on programmable hand-held calculators.

Binding Sites↗
PubMed1983

Chronic antidepressant treatment and central 5-HT synapses.

The present studies have shown that chronic antidepressant treatment with desipramine, imipramine, zimelidine and alaproclate led to adaptive changes in both pre- and postsynaptic 5-hydroxytryptamine (5-HT) receptor mechanisms which appear to result in 5-HT sub- or supersensitivity development depending upon the 5-HT nerve terminal systems analyzed. The results underline the heterogeneity of the central 5-HT neurone systems in their responses to chronic antidepressant treatment. An involvement of 5-HT comodulators is postulated in the actions of antidepressants on central 5-HT synapses. Finally, the results point to the importance of 5-HT neurone systems as targets for the action for antidepressant drugs and they may mediate at least some of the therapeutic activity of antidepressant drugs.

Animals↗
PubMed1983

Quantitative autoradiographic localization of [3H]imipramine binding sites in the brain of the rat: relationship to ascending 5-hydroxytryptamine neuron systems.

Quantitative autoradiography shows that there is a close relationship between [3H]imipramine binding sites and the distribution of 5-hydroxytryptamine (5-HT) neurons in the rat brain. High labeling is observed in the midbrain raphe nuclei, the areas of the dopamine cell groups of the substantia nigra and of the ventral tegmental area of Tsai, the ventral amygdaloid nucleus, the midline thalamic area, and parts of the hypothalmus. Thus, antidepressant drugs that have high affinity for [3H]imipramine binding sites can exert an influence at the 5-HT cell body as well as at the 5-HT nerve terminal level. The present results underline the possibility that the 5-HT and dopamine hypotheses for the mechanism of action of antidepressant drugs are not mutually exclusive, because both 5-HT and dopamine neurons can be regulated by large numbers of [3H]imipramine binding sites.

Animals↗