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C Bendotti

Publications and source records attributed to C Bendotti.

At least 37 records · Page 2Linked to original sources
PubMed1997

Selective up-regulation of protein kinase C epsilon in granule cells after kainic acid-induced seizures in rat.

Kainate-induced seizure activity causes persistent changes in the hippocampus that include synaptic reorganization and functional changes in the mossy fibers. Using in situ hybridization histochemistry, the expression of PKC alpha, PKC beta, PKC gamma, PKC delta and PKC epsilon mRNAs was investigated in the hippocampus of adult rats following seizures induced by a s.c. injection of kainic acid. In CA1 and CA3, we found a significant decrease in PKC gamma mRNA 1 day after kainic acid which persisted for a 2nd day in CA1. None of the other PKC isoform mRNAs were altered in CA1 or CA3. In granule cells, a significant up-regulation specific to PKC epsilon mRNA was observed. One week after kainic acid administration, a marked increase in PKC epsilon immunoreactivity was found that persisted 2 months after kainic acid administration. PKC epsilon immunoreactivity was found associated with mossy fibers projecting to the hilus of the dentate gyrus and to the stratum lucidum of the CA3 field and presumably with the newly sprouted mossy fibers projecting to the supragranular layer. These data provide the first evidence for a long-lasting increase of the PKC epsilon in the axons of granule cells caused by kainate-induced seizures and suggest that PKC epsilon may be involved in the functional and/or structural modifications of granule cells that occur after limbic seizures.

Amygdala↗
PubMed1997

Selective localization of mouse aldehyde oxidase mRNA in the choroid plexus and motor neurons.

Aldehyde oxidase (AO), a protein involved in the catabolism of catecholamines, is the product of a gene potentially responsible for one of the familial forms of the motor neuron disease, amyotrophic lateral sclerosis (ALS). Here, we report on the cloning of a partial cDNA coding for the mouse enzyme. Using this cDNA as a probe, we demonstrate that the AO transcript is expressed in the epithelial component of the choroid plexus. More importantly, in the gray matter, the mRNA is selectively localized in the large motor neurons of the nuclei of facial, motor trigemini and hypoglossus nerves and in the motor neurons of the anterior horns of the spinal cord. This localization is consistent with a possible role of AO in the pathogenesis of ALS.

Aldehyde Oxidase↗
PubMed1997

Acute and chronic treatments with citalopram lower somatostatin levels in rat brain striatum through different mechanisms.

The suggestion that somatostatin is involved in the pathophysiology of obsessive-compulsive disorder and the evidence that selective serotonin reuptake inhibitors show significant antiobsessional effect prompted us to examine the effect of citalopram, a selective and potent serotonin reuptake inhibitor, on the somatostatinergic system in different brain regions of the rat. A single intraperitoneal injection of 10 mg/kg citalopram significantly reduced somatostatin levels in the striatum and nucleus accumbens after 4 but not 1, 8, or 24 h. No changes were found in hippocampus. In addition, we found that the K+-evoked overflow of somatostatin-like immunoreactivity from striatal slices was significantly increased 1 h after a single injection of citalopram and was still higher, although not significantly, 4 h after the drug injection. Levels of preprosomatostatin mRNA were unchanged in striatum and accumbens 1 and 4 h after a single drug administration. In rats treated with citalopram (10 mg/kg i.p.) twice daily for 14 days, the levels of somatostatin and its mRNA were significantly decreased in the striatum but not in other brain regions 24 h after the last dose. No change was found in the basal or K+-evoked overflow of somatostatin-like immunoreactivity at 1, 4, and 24 h after the last drug injection. These results suggest that acute and chronic treatment with citalopram reduces somatostatin levels in striatum by different mechanisms. Whereas a single dose of the drug reduces somatostatin levels by increasing the release of the peptide, repeated drug treatment reduces the biosynthesis of somatostatin.

Animals↗
PubMed1997

Relationship between GAP-43 expression in the dentate gyrus and synaptic reorganization of hippocampal mossy fibres in rats treated with kainic acid.

Kainic acid-induced seizures, in adult rats produce neurodegeneration in the hippocampus followed by sprouting of the mossy fibres in the inner molecular layer of the dentate gyrus and changes in GAP-43 expression in the granule cells. In the present study we observed that 4 days after kainic acid injection a dense plexus of silver-impregnated degenerating terminals detected by Gallyas's method and a decrease of GAP-43 immunostaining was observed in the inner molecular layer of the dentate gyrus indicating deafferentiation of this region. This was associated with the formation of an intense GAP-43 immunostained band in the supragranular layer. MK-801, a non-competitive inhibitor of the NMDA receptor, which partially inhibited the behavioural seizures induced by KA, also protected from the inner molecular layer deafferentation and markedly reduced the expression of GAP-43 mRNA in the granule cells and the intense GAP-43 immunostained band in the supragranular layer, suggesting a relationship among these events. Two months after kainic acid injection the intense supragranular GAP-43 positive band was no longer evident but the whole inner molecular layer appeared more labelled in association with the formation of the collateral sprouting of the mossy fibres in the inner molecular layer as detected by Timm's staining. These effects were also markedly reduced by the pretreatment with MK-801. Taken together, these experiments indicate for the first time a direct relationship between the increase of GAP-43 immunostaining in the inner molecular layer of the dentate gyrus and the collateral sprouting of mossy fibres in this district in response to kainic acid induced seizures. This further supports the hypothesis that the early induction of GAP-43 in granule cells may be one of the molecular mechanisms required for the synaptic reorganization of the mossy fibres.

Animals↗
PubMed1996

Cycloheximide inhibits kainic acid-induced GAP-43 mRNA in dentate granule cells in rats.

We have previously shown that kainic acid-induced seizures in adult rats caused an up-regulation of GAP-43 mRNA in the granule cells of the hippocampus, suggesting an involvement of this protein in the kainic acid-induced sprouting of mossy fibres. To determine whether this effect was dependent on the synthesis of proteins activated under these experimental conditions we examined the effect of cycloheximide, a protein synthesis inhibitor, on kainic acid-induced GAP-43 mRNA. Cycloheximide, injected s.c. 2 h but not 8 h after kainic acid, markedly reduced the increased expression of GAP-43 mRNA in granule cells. These results suggest that a rapid mechanism involving new protein synthesis is activated by kainic acid to induce GAP-43 in the granule cells and possibly trigger the structural remodeling of mossy fibres.

Animals↗
PubMed1996

Developmental and plasticity-related differential expression of two SNAP-25 isoforms in the rat brain.

In this article we study the relationship between the expression pattern of two recently identified isoforms of the 25-kD synaptosomal-associated protein (SNAP-25a and SNAP-25b) and the morphological changes inherent to neuronal plasticity during development and kainic acid treatment. SNAP-25 has been involved in vescicle fusion in the nerve terminal, and most likely participates in different membrane fusion-related processes, such as those involved in neurotransmitter release and axonal growth. In the adult brain, SNAP-25b expression exceeded SNAP-25a in distribution and intensity, being present in most brain structures . Moderate or high levels of SNAP-25a hybridization signal were found in neurons of the olfactory bulb, the layer Va of the frontal and parietal cortices, the piriform cortex, the subiculum and the hippocampal CA4 field, the substantia nigra/pars compacta, and the pineal gland, partially overlapping SNAP-25b mRNA distribution. In restricted regions of cerebral cortex, thalamus, mammillary bodies, substantia nigra, and pineal glands the two isoforms were distributed in reciprocal fashion. During development SNAP-25a mRNA was the predominant isoform, whereas SNAP-25b expression increased postnatally. The early expression of SNAP-25a in the embryo and the decrease after P21 is suggestive of a potential involvement of this isoform in axonal growth and/or synaptogenesis. This conclusion is indirectly supported by the observation that SNAP-25a mRNA, but not SNAP-25b mRNA, was upregulated in the granule cells of the adult dentate gyrus 48 hours after kainate-induced neurotoxic damage of the hippocampal CA3-CA4 regions. Increase of SNAP-25 immunoreactivity was observed as early as 4 days after kainate injection within the mossy fiber terminals of the CA3 region, and in the newly formed mossy fiber aberrant terminals of the supragranular layer. These data suggest an isoform-specific role of SNAP-25 in neural plasticity.

Animals↗
PubMed1996

p-Chlorphenylalanine changes serotonin transporter mRNA levels and expression of the gene product.

After a single intraperitoneal injection of the irreversible tryptophan hydroxylase inhibitor p-chlorophenylalanine (PCPA; 300 mg/kg), there was a rapid down-regulation of serotonin (5-HT) transporter mRNA levels in cell bodies. This change was significant at 1 and 2 days after PCPA administration within the ventromedial but not the dorsomedial portion of the dorsal raphe nucleus. Seven days after PCPA treatment, 5-HT transporter mRNA levels were significantly elevated compared with controls in both regions of the dorsal raphe nucleus. PCPA administration produced no change in the [3H]citalopram binding and synaptosomal [3H]5-HT uptake in terminal regions at 2 and 7 days after treatment but significantly reduced both these parameters by approximately 20% in the hippocampus and in cerebral cortex 14 days after PCPA administration. The striatum showed a lower sensitivity to this effect. No significant changes were observed in the levels of [3H]citalopram binding to 5-HT cell bodies in the dorsal raphe nucleus. In the same animals used for 5-HT transporter mRNA level measurements, levels of tryptophan hydroxylase mRNA in neurons of the ventromedial and dorsomedial portions of the dorsal raphe nucleus were increased 2 days after PCPA administration and fell to control levels 7 days after injection in the ventromedial region but not in the dorsomedial portion of the dorsal raphe nucleus, where they remained significantly higher than controls. Altogether, these results show that changes in 5-HT transporter mRNA are not temporally related to changes in 5-HT transporter protein levels. In addition, our results suggest that the 5-HT transporter and tryptophan hydroxylase genes are regulated by different mechanisms. We also provide further evidence that dorsal raphe 5-HT neurons are differentially regulated by drugs, depending on their location.

Animals↗
PubMed1994

Ultrastructural immunolocalization of GAP-43 in the sprouted mossy fibres of kainic acid lesioned rats.

Kainic acid (KA)-induced seizures in adult rats have been reported to cause sprouting of mossy fibres in the inner molecular layer (IML) of the dentate gyrus. In the present study, using electron microscopic immunostaining for GAP-43 we found that 3 months after KA treatment, several GAP-43 positive terminals in the IML showed structural characteristics of mossy fibre boutons. No GAP-43-positive mossy fibre terminals were found in the normal projection areas of granule cells, thus indicating that newly synthesized GAP-43 is transported predominantly in the axonal branches actively undergoing remodelling. These results provide evidence of the involvement of GAP-43 in the structural remodelling of mossy fibres, and suggest a role of this protein in the functional activity of the sprouted mossy fibres as a consequence of KA-induced seizures.

Animals↗
PubMed1994

Chronic D-fenfluramine decreases serotonin transporter messenger RNA expression in dorsal raphe nucleus.

In situ hybridization was used to measure the effects of chronic fenfluramine administration on serotonin transporter messenger RNA expression in cells of the dorsal raphe nucleus complex. Fenfluramine produced a significant, but transient, down-regulation of serotonin transporter mRNA in cells which lie in the ventral portion of the dorsal raphe nucleus, but not in the dorsal part of the dorsal raphe nucleus. Our findings suggest that cells which lie in the ventral part of the dorsal raphe nucleus are more sensitive to the effects of chronic fenfluramine administration, but that fenfluramine does not cause long-term changes in gene expression in serotonin cell bodies.

Animals↗
PubMed1994

Expression of GAP-43 in the granule cells of rat hippocampus after seizure-induced sprouting of mossy fibres: in situ hybridization and immunocytochemical studies.

The axonal growth-associated protein GAP-43 is believed to play some role in the synaptic remodelling that takes place in the hippocampus of adult rats after certain experimental lesions. GAP-43 mRNA is highly expressed in adult CA3 pyramidal cells but almost absent in the dentate granule cells. We analysed whether the sprouting of granule cell axons, the mossy fibres of the hippocampus, caused by kainic acid-induced seizures in adult rats was associated with any induction of GAP-43 mRNA in granule cells and with any changes in the immunostaining pattern of GAP-43 in the hippocampus. Increased GAP-43 mRNA expression was found to be induced in granule cells 18, 24 and 30 h after a systemic injection of kainic acid which induced generalized seizures in adult rats, and returned to control levels by 48 h post-treatment. No effect was observed in other regions of the hippocampus. However, when kainic acid was injected into 15-day-old rats, which responded with generalized seizures but no sprouting of mossy fibres, there was no induction of GAP-43 mRNA in the granule cells, suggesting a close relation between GAP-43 expression and sprouting of these cells. Seven days after kainic acid injections, GAP-43 immunostaining was decreased in the inner molecular layer of the dentate gyrus except for a thin supragranular band, whereas 30 days after treatment all animals showed increased GAP-43 immunoreactivity in the whole inner molecular layer.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Potential antidepressant properties of SR 57746A, a novel compound with selectivity and high affinity for 5-HT1A receptors.

SR 57746A, 4-(3-trifluoromethylphenyl)-N-[2-(naphth-2-yl)ethyl]-1,2,3,6- tetrahydropyridine HCl, was studied for its specific 5-HT1A receptor agonist action and antidepressant-like effects in the rat. The compound showed a high affinity for 5-HT1A specific binding sites in the rat hippocampus (IC50 3 nM), moderate affinity (10(-7)-10(-6) M) for dopamine D2 receptor, 5-HT uptake, 5-HT2 and alpha 1-adrenoceptor binding sites and practically no effect on binding sites of monoamine, GABAA, benzodiazepine and histamine receptors. It inhibited forskolin-stimulated adenylate cyclase activity in rat hippocampal membranes at concentrations of 10(-6) and 10(-5) M. The effect of 10(-6) M SR 57746A on forskolin-stimulated adenylate cyclase activity was completely antagonized by 10(-6) M (-)-propranolol. Administered per os as a three-dose course to rats, SR 57746A significantly increased struggling in the forced swimming test at doses from 0.3 to 3 mg/kg. Single doses had no such effect. The effect of a three-dose course with 1 mg/kg SR 57746A on rats' struggling was antagonized by pretreatment with 5 mg/kg i.p. metergoline, a non-selective 5-HT receptor antagonist, and by 20 mg/kg i.p. (-)-propranolol, an antagonist at 5-HT1 receptors. Three oral doses of 100 mg/kg parachlorophenylalanine, an inhibitor of 5-HT synthesis, and 100 mg/kg i.p. (+/-)-sulpiride, an antagonist at dopamine D2 receptors, also antagonized the effect of SR 57746A in the forced swimming test. The results show that SR 57746A has selectivity and high affinity for 5-HT1A receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1994

Does GFAP mRNA and mitochondrial benzodiazepine receptor binding detect serotonergic neuronal degeneration in rat?

Intracerebroventricularly (ICV) injected 5,7-dihydroxytryptamine (5,7-DHT), which reduced by 70-90% forebrain serotonin levels, significantly raised glial fibrillary acidic protein (GFAP) mRNA levels in the hippocampus and nucleus raphe dorsalis 5 days but not 15 days after the lesion. A significant increase of mitochondrial benzodiazepine receptors (MBR), measured by binding autoradiography of 3H-PK 11195, was found in the nucleus raphe dorsalis 5 and 15 days after the ICV 5,7-DHT and also in the hippocampus, ventral tegmental area, and substantia nigra at 15 days. No significant effect was observed in the striatum and cortex for either GFAP mRNA or MBR binding. Unlike the ICV route, bilateral injection of 5,7-DHT into the medial forebrain bundle, which caused a 65-90% reduction of serotonin levels in different forebrain regions, significantly raised GFAP mRNA and MBR binding only at the site of injection with no effect in hippocampus, striatum, and cortex. MBR binding slightly increased in the nucleus raphe dorsalis 15 days after the lesion. High doses of d-fenfluramine (10 mg/kg intraperitoneally twice daily for 4 days) caused 80-90% reduction of serotonin levels 5 days after the last injection but did not change the GFAP mRNA or the MBR binding in any of the brain regions considered. These findings suggest that the effect of 5,7-DHT on microglial and glial markers is probably related to a nonspecific interaction with other neuronal systems besides the serotonin or to direct interaction with glial cells; the use of these parameters for detecting selective degeneration of serotonin axons presents some obvious limitations.

5,7-Dihydroxytryptamine↗
PubMed1993

Increased expression of preproneuropeptide Y and preprosomatostatin mRNA in striatum after selective serotoninergic lesions in rats.

The levels of neuropeptide Y and somatostatin may change when serotoninergic neurotransmission is altered in different brain regions. To assess whether serotonin regulates the synthesis of these peptides, we measured the levels of preproneuropeptide Y (ppNPY) and preprosomatostatin (ppSOM) mRNA in different brain regions after intracerebroventricular injection of 5,7-dihydroxytryptamine (5,7-DHT), a selective serotonin neurotoxin. The mRNA of these peptides significantly increased in the striatum but not in hippocampus and frontal cortex. It thus appears that serotonin has an inhibitory effect on the biosynthesis of neuropeptide Y and somatostatin in striatum whereas it probably acts by stimulating the release of these peptides in hippocampus and frontal cortex.

5,7-Dihydroxytryptamine↗
PubMed1993

Increased expression of GAP-43, somatostatin and neuropeptide Y mRNA in the hippocampus during development of hippocampal kindling in rats.

The expression and distribution of the mRNA coding for the growth-associated protein-43 (GAP-43), a putative marker for neuritic growth, for preprosomatostatin and the preproneuropeptide Y (ppNPY) were analysed in the rat hippocampus during the development of hippocampal kindling by an in situ hybridization technique and computer-assisted grain counting in the cell. The levels of GAP-43 mRNA increased significantly in the CA3 pyramidal neurons and hilar polymorphic neurons of the dentate gyrus 2 days after stage 2 of kindling (preconvulsive stage) but not stage 5 (full seizure expression) in the stimulated hippocampus. The distribution of GAP-43 mRNA was the same in the hippocampus of kindled rats as in sham-stimulated animals. Preprosomatostatin mRNA and ppNPY mRNA contents rose significantly in the hilar polymorphic neurons of the dentate gyrus of the stimulated and contralateral hippocampus at both stages of kindling, with the greatest effect at stage 5. In addition, the number of ppNPY mRNA neurons in the fascia dentata was significantly higher in kindled rats than in controls, but there were no differences in the number of preprosomatostatin mRNA-positive cells. Preprosomatostatin and ppNPY mRNAs were also increased in the neurons of the stratum oriens of the CA1-CA3 subfield of fully kindled animals, whereas at stage 2 only neurons of the CA1 stratum oriens showed a significant increase of preprosomatostatin mRNA. No changes in preprosomatostatin and ppNPY mRNA expression were observed in the various regions of the hippocampus after a single afterdischarge or 1 month after stage 5.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Distribution of GAP-43 mRNA in the adult rat brain.

Regional distribution of gene expression of the axonal growth-associated protein, GAP-43, was studied in adult rat brains by in situ hybridization autoradiography to determine the features of mature neuronal populations that synthesize GAP-43 protein. Such synthesis appears to correlate with axonal growth during maturation and regrowth after axotomy. In most adult neurons, the sharp decline in GAP-43 gene expression implies a reduced capacity for axonal growth. Neurons capable of extending axonal knobs in the absence of injury may indicate a "plasticity" underlying dynamic processes of interaction between neurons and their synaptic targets. Antisense and sense (control) riboprobes were used on serial sections in the three principal axes, and the magnitude of hybridization signal was examined to determine regional patterns. GAP-43 mRNA levels are pronounced in diverse neuronal groups including the locus coeruleus, raphé nn., dopaminergic nigral and ventral tegmental nn., mitral cells, hippocampal CA3, inferior olivary n., vagal motor n. and other parasympathetic preganglionic neurons, select thalamic midline and intralaminar nn., several specific nn. of the hypothalamus and basal forebrain, the granular layer of cerebellar cortex, the infragranular neocortex, and the granular olfactory paleocortex; there is a substantial range in the magnitude of expression. Regions revealing minimal signal include most thalamic sensory relay nuclei, the granule neurons of the olfactory bulb and dentate gyrus, and the caudate and putamen. Possible concomitants of GAP-43 expression include regulation of ion flux and neurotransmitter release. Those neurons with long, extensively dispersed and numerous synaptic connections display the strongest signals and may possess the greatest propensity for continuous growth and turnover of their axon terminals, in contrast to short-axon and specific projection neurons exhibiting minimal levels. These data may enable inferring which populations display normal or experimentally induced axonal growth.

Animals↗
PubMed1993

Perinatal morphine treatment inhibits pruning effect and regeneration of serotoninergic pathways following neonatal 5,7-HT lesions.

Lesion of the serotoninergic system in neonate rats is an ideal model for assessing the activity of chemical substances capable of affecting neuronal plasticity and regeneration (Jonsson et al., Dev Brain Res 16: 171-180, 1984). Treatment of newborn rats within 6 hr from birth with the selective neurotoxin 5,7-dihydroxytryptamine causes degeneration of the most distal serotoninergic axons. In our experimental conditions we have observed that after such neurotoxic treatment there is spinal cord denervation, which is particularly remarkable in the lumbar segment. This degenerative event is followed by gradual regeneration of the lesioned axons, with good reinnervation of the entire cord within 8 weeks. The degeneration-regeneration process is correlated with a transient hyperinnervation of the pons-medulla and hypothalamus by the short collaterals (pruning effect), as evidenced by increased serotonin content. Perinatal morphine exposure markedly impairs serotonin regeneration in the spinal cord. In addition, opiate treated rats are more susceptible to lesions, as shown by the neurotoxin induced denervation of the cortex, pons-medulla, and hypothalamus, which does not occur in lesioned controls. Therefore, our observations suggest that perinatal exposure to morphine affects the plasticity and regeneration of the developing serotoninergic system by increasing its susceptibility to neurotoxic lesions and reducing its regenerative capacity.

5,7-Dihydroxytryptamine↗
PubMed1993

In situ hybridization reveals specific increases in G alpha s and G alpha o mRNA in discrete brain regions of morphine-tolerant rats.

In situ hybridization histochemistry has been used to detect the basal distribution of mRNA encoding the alpha subunit of Gs, Go and Gi2 proteins throughout the rat brain. Based on these data we investigated the effect of chronic morphine on the content of these G protein alpha subunits mRNA. We observed an increase in the expression of alpha s and alpha o messages of chronically morphine-treated animals, while no changes were seen in alpha i2 mRNA. Specifically a 30% increase in expression for alpha s was seen only in the paraventricular nucleus of hypothalamus and a 20% elevation for alpha o was detected in the claustrum and endopiriform nucleus. Immunoblotting analysis was used to correlate the changes in alpha s and alpha o messages with equivalent changes in protein levels. Chronic morphine significantly increased alpha s amounts in the hypothalamus (70%), and produced a minor elevation (30%) in G alpha o levels in the olfactory area. Our results indicate that in discrete brain regions altered G protein expression is part of the adaptive changes underlying opiate tolerance.

Animals↗