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A Consolazione

Publications and source records attributed to A Consolazione.

At least 19 recordsLinked to original sources

Time course of nigrostriatal system changes after tract hemisection and effects of ganglioside treatment: a multiple retrograde fluorescent tracing study.

The postlesion phenomena of nigrostriatal neurons following partial tract hemisection have been studied with retrograde axonal transport of dyes in rats treated with saline or GM1 ganglioside (30 mg/kg, i.p., daily for varying times). The time course of the plastic changes in both experimental animal groups was determined by a double retrograde fluorescent tracing technique, utilizing Fast blue (FB) as prelesion tracer, and Diamidino yellow (DY) as postlesion tracer. The data show that the number of nigral cells retrogradely labeled by the prelesion intrastriatal injection of FB declined progressively to 50% of their initial number over 3 weeks. The ganglioside treatment did not significantly influence this temporal pattern of labeled cell loss. By DY-labeling, an almost complete block of the retrograde axonal transport was observed up to 1 week postlesion and only after 3 weeks a partial recovery was evident, positively influenced by the GM1 treatment. Therefore, together with the findings on nigrostriatal cell loss, these data indicate that ganglioside treatment favors and/or accelerates the recovery of axonal transport of surviving nigral neurons but does not significantly affect their degenerative rate in the first 3 weeks after the lesion.

Amidines↗

Lesioning and recovery of the serotoninergic hippocampal afferents: differential effects of GM1 ganglioside.

The effects of administration of GM1 ganglioside on the content of 5-HT and of 5-HIAA in the hippocampus after two different types of lesions of the serotoninergic afferents to the hippocampus were studied. The first type of lesion consisted in severing the dorsal hippocampal afferents. This caused a monolateral decrease of the content of 5-HT and of 5-HIAA in the hippocampal by 60 and 38%, respectively. Since a partial spontaneous recovery occurred after 40-60 days, this model has been used in the past to study sprouting phenomena in the 5-HT system. Daily intraperitoneal administration of GM1 ganglioside (30 mg/kg), for up to 60 days, did not modify this partial recovery. The second lesion consisted of electrolytic damage to a mesencephalic area, where scattered 5-HT cells projecting to the hippocampus are known to be located. The content of 5-HT and 5-HIAA in the hippocampus, ipsilateral to this lesion, decreased by 37 and by 26%, respectively. Administration of GM1 ganglioside (30 mg/kg/day for 6-14 days) partially antagonized the decrease of both 5-HT and 5-HIAA induced by the lesion. These data are in agreement with the view that gangliosides may reduce neuronal injury after mechanical lesions, with a mechanism which is probably not related to neuronal sprouting.

Afferent Pathways↗

Lesioning and recovery of the serotoninergic projections to the hippocampus.

The time course of the changes of the hippocampal 5-hydroxytryptamine (5-HT) system after a lesion of the dorsal afferents to this brain area was studied by measuring the content of 5-HT and of 5-hydroxyindoleacetic acid (5-HIAA) in the dorsal, medial and ventral hippocampus. Furthermore, the binding sites for [3H]5-HT, [3H]ketanserin, [3H]imipramine and [3H]mianserin and a 5-HT-mediated behavior (head-twitch responses) were studied in controls and in animals bearing such a lesion. The contents of 5-HT and of 5-HIAA are higher in the ventral than in the dorsal hippocampus. Seven days after the lesion the 5-HT content decreases by 78% in the dorsal and by 50% in the ventral hippocampus. However, 60 days later, a partial recovery, possibly due to a collateral sprouting, does occur. The ratios between 5-HIAA and 5-HT are also increased 10, 14 and 21 days after the lesion, suggesting an increased utilization of the amine by the remaining neuronal terminals. The Bmax of the recognition sites for [3H]5-HT and [3H]mianserin, but not those for [3H]ketanserin are increased 10 days after the lesion and this increase lasts at least 30 days. Finally, starting 10 days after surgery and lasting for 40 days, a 5-HT-mediated behavior (head-twitch responses) shows supersensitivity. These results suggest that important changes occur in the 5-HT innervation of the hippocampus after a mechanical lesion: among these we showed a slow collateral sprouting, an increased utilization of the amine and a supersensitivity of 5-HT receptors.

Animals↗

Selective enhancement of tubulin gene expression and increase in oligo(dT)-bound RNA in the rat brain after nigrostriatal pathway unilateral lesion and treatment with ganglioside.

Partial hemitransection of the rat nigrostriatal pathway has been applied to study changes in the expression of tubulin and actin cytoskeletal genes. RNA was isolated from ipsilateral and contralateral structures of substantia nigra and striatum tissues of lesioned or sham-operated animals by a combined proteinase K and oligo(dT)-cellulose affinity purification procedure. A significant increase in the oligo(dT)-cellulose-eluted RNA was observed in the lesioned substantia nigra and striatal tissues compared to naive controls. By 5 days, the RNA content of the lesioned nigra reached a value of 96-114.5 micrograms/mg DNA compared to 45.7-52.9 micrograms/mg DNA. Administration of GM1 gangliosides at daily intervals resulted by day 5 in a further increase (131.8-141.5 micrograms/mg DNA) in the RNA content of the lesioned but also of the sham-operated (81.9-97.8 micrograms/mg DNA) animals. By 18 hr, the lesioned nigra exhibited a four-fold increase in tubulin messenger RNA (mRNAtub) gene expression in comparison to the sham-operated animals. The substantia nigra tissue of GM1-treated animals exhibited a hybridization value for mRNAtub twice as high compared to GM1-untreated, lesioned animals. The effect of GM1 appeared selective for alpha-tubulin and beta-tubulin compared to actin transcript. The latter was also elevated in the lesioned nigra tissue above the naive or sham-operated animals. The data suggest that, after injury, cytoskeletal RNA transcripts are elevated and that GM1 may play a role in the regulation of their steady-state levels.

Animals↗

Reparative processes in aged brain.

Endogenous neurotrophic factors have been proposed to play an important role in degenerative diseases and aging. In aged rats, neurotrophic activity induced by partial lesion of nigro-striatal pathways seems to be lower compared to young rats when assayed in vitro on cultured mesencephalic dissociated neuronal cells. In parallel experiments, we could also observe an age-dependent delay in spontaneous recovery of striatal tyrosine hydroxylase activity after lesion. Both experimental evidences suggest a low-potential neuroplasticity in aged rats. Nevertheless, the aging brain seems to be responsive to pharmacological manipulation. Long-term phosphatidylserine treatment has been shown to maintain the integrity of neuronal structures altered by the aging process. Putative mechanisms of action underlying these effects are presented.

Aging↗

Evidence for crossed catecholaminergic nigrostriatal projections by combining wheat germ agglutinin-horseradish peroxidase retrograde transport and tyrosine hydroxylase immunocytochemistry.

After unilateral injections of wheat germ agglutinin-horseradish peroxidase into the rat caudate-putamen, a few retrogradely labeled neurons were found in the contralateral pars compacta of the substantia nigra. These contralaterally projecting nigral cell bodies also immunoreacted positively to a specific tyrosine hydroxylase antiserum. We conclude that crossed catecholaminergic nigrostriatal projections may contribute to the reciprocal regulation exerted by the two nigrostriatal dopaminergic systems.

Animals↗

Cholinergic projections from the midbrain and pons to the thalamus in the rat, identified by combined retrograde tracing and choline acetyltransferase immunohistochemistry.

The distribution of cholinergic neurons in the midbrain and pons which project directly to the thalamus was investigated in the rat using a procedure which allows the simultaneous detection of retrogradely transported horseradish peroxidase (HRP) and immunohistochemical demonstration of choline acetyltransferase (ChAT) in the same neurons. HRP injections were placed in the dorsal half of the anterior third of the thalamus on one side which included the anteroventral nucleus as well as portions of the rostral intralaminar and reticular nuclei. These thalamic nuclei showed the highest density of immunohistochemically detectable cholinergic fibers. Neurons containing both HRP and ChAT, which represented cholinergic neurons projecting directly to the thalamus, were found in the midbrain and pons in the lateral tegmental reticular formation, parabrachial region and lateral dorsal tegmental nucleus. Ipsilateral to the injection site over 91% of the HRP labeled neurons in all of these regions were cholinergic, while an average of 60% of the cholinergic neurons had transported HRP. Contralateral to the injection site 5-6% of the cholinergic neurons in these regions were also retrogradely labeled. These findings demonstrate direct cholinergic projections to the thalamus from neurons in several regions in the tegmentum and suggest that tegmental projections to the thalamus are predominantly cholinergic.

Animals↗

Choline acetyltransferase activity in the rat trigeminal system.

Choline acetyltransferase activity was investigated in the superior cervical ganglia and in six microdissected regions of the medulla oblongata of the rat ipsilateral and contralateral to electrolytic lesions of the trigeminal sensory ganglia (Gasserian). Electrolytic lesions of the Gasserian ganglia failed to modify levels of enzymatic activity in all structures studied. This result would be an argument against the existence of a major cholinergic population of sensory neurones in the trigeminal system.

Animals↗

Serotonin-containing projections to the thalamus in the rat revealed by a horseradish peroxidase and peroxidase antiperoxidase double-staining technique.

The retrograde transport of horseradish peroxidase (HRP) has been used in combination with peroxidase antiperoxidase (PAP) immunocytochemistry in order to investigate serotonin-containing projections to the thalamus of the rat. Sections were histochemically stained to reveal retrogradely transported HRP and then PAP immunostained using a monoclonal anti-serotonin (5-HT) antibody. Following HRP injections into the ventral thalamus, retrogradely labelled cells were observed in a number of sites in the brainstem and including areas known to be rich in 5-HT-containing neurons. At rostral levels of the dorsal raphe nucleus, retrogradely labelled cells were observed both on the midline and in a distinct lateral group extending diffusely into the periaqueductal gray (PAG). In both of these areas many 5-HT-immunoreactive HRP retrogradely labelled neurons were observed. However, except for the most rostral levels of the dorsal raphe nucleus, such double-labelled cells represented only a small proportion of the total population of 5-HT-immunoreactive neurons. In the lateral group, the retrograde labelling was mainly unilateral to the injection site but some contralateral labelling was also seen. At caudal levels of the dorsal raphe nucleus, retrogradely labelled cells were observed predominantly in the lateral group. At the level of the dorsolateral tegmental nucleus, few 5-HT or 5-HT/HRP labelled cells were observed in the lateral group, although HRP retrogradely labelled neurons were present. Double-stained cells were detected also in the medial raphe nucleus (corresponding to the B8 cell group according to the nomenclature of Dahlström and Fuxe), among the fibres of the medial lemniscus (B9), and in nucleus raphe pontis (B5).

Animals↗

The functional recovery of damaged brain: the effect of GM1 monosialoganglioside.

In the present study the topology and the biochemical mechanisms underlying the functional recovery of the dopaminergic nigrostriatal system is further analyzed. Rats with unilateral hemitransection were treated with 30 mg/kg GM1 monosialoganglioside or with its internal ester derivative for different periods of time. GM1 enhances 3H-dopamine uptake in striatal synaptosomes of the lesioned side, and the enhancement of dopamine uptake precedes that of striatal tyrosine hydroxylase activity. The above biochemical effects are accompanied by changes in behavioral- and electrophysiological-related parameters. The effect of GM1 on striatal tyrosine hydroxylase of the lesioned side disappears when the ascending dopaminergic fibers are extensively lesioned. This suggests that the source of regrowing dopaminergic nerve terminals in the striatum of partially lesioned rats resides mainly in the intact axons remaining in the ipsilateral side. When GM1 is injected into partially lesioned rats kept in darkness, no effect on tyrosine hydroxylase activity is observed. This indicates that the mechanism through which GM1 acts involves a normal light-dark cycle.

Animals↗

Effect of GM1 ganglioside treatment on the recovery of dopaminergic nigro-striatal neurons after different types of lesion.

The effect of GM1 ganglioside treatment on the recovery of biochemical and behavioral parameters which define the activity of nigro-striatal dopaminergic systems has been investigated in rats after different types of lesion. GM1 favours the recovery of tyrosine-hydroxylase activity, of the number and affinity of 3H-N-n-propyl-norapomorphine binding sites in the striatum of the lesioned side and reduces the apomorphine-induced rotational behavior after mechanical (i.e. unilateral hemitransection) but not after chemical (i.e. 6-OHDA injected in the substantia nigra) lesion. The source of regrowing dopaminergic nerve terminals in the striatum after hemitransection is mainly a response of intact remaining axons of the ipsilateral side. Moreover the contralateral nigro-striatal systems seems to play, through intrathalamic connections, an important role in regulating the GM1-induced increase of the tyrosine-hydroxylase activity.

Animals↗

Immunocytochemical detection of serotonin with monoclonal antibodies.

The development of the monoclonal antibody YC5/45 HLK (YC5/HLK) against a 5HT-bovine seroalbumin immunogen and its application for immunocytochemistry is described. The YC5/HLK antibody is the product of a rat x rat hybrid myeloma, producing a heavy chain and two light chains. In hemagglutination tests, the antibody cross-reacts to entirety with dopamine, serotonin, and tryptamine at high concentrations. The serotonin-albumin conjugate is 20,000 times more effective in displacing the binding antibody, while albumin itself goes unrecognized by the antibody. In fixed preparations of brain tissue, immunofluorescence is observed only in neurons known to contain serotonin, while no reaction is observed in dopamine-rich neurons. All immunofluorescence is extinguished by the use of agents that inhibit the biosynthesis of 5HT, but not of the catecholamines.

Animals↗

Effect of L-5HTP and drugs acting on serotonin metabolism in various myoclonic syndromes.

Ten patients affected by various myoclonic syndromes were tested with drugs acting on cerebral serotonin metabolism and with clonazepam (CZP). After L5HTP or serotonergic drugs administration a clear cut improvement was observed in the 2 patients affected by Ramsay-Hunt syndrome, while the patients with myoclonic epilepsy have shown no effect (3 cases) or negative response (1 case). Methysergide was active only in 1 patient affected by progressive erratic myoclonus who had a striking worsening of clinical picture. The main side effects observed were: gastrointestinal distress (L5HTP--4 patients, fenfluoramine--2, quipazine--1, methysergide--2) and cutaneous rash (quipazine--1 case). These results support the possible implication of the serotonergic system in the pathogenesis of myoclonus other than post-anoxic.

5-Hydroxytryptophan↗