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G Leanza

Publications and source records attributed to G Leanza.

34 records · Page 2Linked to original sources
PubMed1993

Basal forebrain grafts in the hippocampus and neocortex: regulation of acetylcholine release.

The regulation of acetylcholine (ACh) release from cholinergic neurons transplanted to the hippocampus or neocortex was studied by microdialysis in awake rats. Fetal basal forebrain tissue was implanted as a cell suspension or solid graft into the fimbria-fornix-lesioned hippocampus, or as a cell suspension into the frontal cortex after excitotoxic lesion of the nucleus basalis. Several months after transplantation, microdialysis probes were implanted in areas of the hippocampus or frontal cortex reinnervated by the grafts. The grafts restored lesion-induced deficits in steady-state ACh release up to normal or above normal levels in both hippocampus and frontal cortex. The responses to KCl and tetrodotoxin suggested that the ACh release exhibited normal firing-dependent properties. By applying various behaviorally arousing stimuli that normally activate the basal forebrain projection systems, we wished to investigate the functional integration of the grafts in the host brain. In the hippocampus, sensory stimulation, immobilization stress and motor activity all resulted in increased release of graft-derived ACh amounting to 25-65% of the normal response. Variations in ACh levels during the day-night cycle was, however, not observed in the grafted rats. In the frontal cortex, immobilization enhanced the graft-derived ACh release (60% of normal response), whereas the response to sensory stimulation did not reach significance. Since the activity of the normal basal forebrain projection systems is under influence of monoaminergic brainstem afferents, we investigated the effects of systemic administration of amphetamine or apomorphine on ACh release in the hippocampus. Both drugs produced increases in graft-derived ACh release although the response was variable and less pronounced than normal. In conclusion, the graft-derived ACh release was affected by behavioral manipulations and catecholaminergic drugs that normally modify cholinergic septo-hippocampal and basalo-cortical activity. This strongly suggests a high degree of functional integration of the graft in the host brain allowing for a regulated release of transmitter that can be adjusted during ongoing behavior.

Acetylcholine↗
PubMed1993

Functional activity of intrahippocampal septal grafts is regulated by catecholaminergic host afferents as studied by microdialysis of acetylcholine.

Previous microdialysis experiments have shown that acetylcholine (ACh) release from septal grafts in the hippocampus of awake rats is influenced by the behaviour of the animals, which strongly suggests that the host brain can exert a regulatory control over the activity of the grafted neurons. Since the activity of the normal septo-hippocampal cholinergic system is likely to be regulated, in part, by brainstem catecholaminergic afferents, we wished to study the effect of catecholaminergic drugs on ACh release in the hippocampus reinnervated by septal grafts. Rats were subjected to a unilateral aspirative fimbria-fornix (FF) transection and grafted with tissue from the fetal septal-diagonal band area, either as a cell suspension injection into the depth of the hippocampus or as a solid implant in the FF lesion cavity. Microdialysis of ACh release was carried out 17-20 months after transplantation in awake, freely-moving animals. The reduction in steady-state ACh overflow induced by the FF lesion (-81%) was restored to normal or above normal levels in rats with either solid or suspension grafts. In normal rats, systemic administration of apomorphine (2.0 mg/kg, s.c.) or amphetamine (2.5 mg/kg, i.p.) caused a 3.7 (+189%) or 7.8 (+301%) pmol/15 min increase in ACh overflow compared to the previous baseline level, respectively. The drug-induced increases in ACh levels in the FF-lesioned controls was substantially lower than normal (86-89% reduction). Both apomorphine and amphetamine resulted in an approximately two-fold increase in hippocampal ACh release in rats with suspension grafts. These responses were significantly increased over those seen in rats with FF lesions only, but they tended to be lower and more variable than normal. Rats with solid septal grafts responded significantly stronger than FF lesion controls to amphetamine with two-fold increased ACh overflow, whereas the response to apomorphine was less clear-cut. Pretreatment with the catecholamine synthesis blocker alpha-methyl-p-tyrosine (AMPT; 200 mg/kg x 3) did not affect steady-state or apomorphine-stimulated release of ACh in any of the groups, whereas the effect of amphetamine was abolished in both normal and grafted rats. The results suggest that ACh release derived from septal grafts in the hippocampus, similar to the normal septo-hippocampal system, can be affected by manipulations of the host catecholaminergic systems. This mechanism may, at least in part, underlie the ability of the host brain to influence and control the activity of grafted cholinergic neurons.

Acetylcholine↗
PubMed1993

Compensatory changes of in vivo acetylcholine and noradrenaline release in the hippocampus after partial deafferentation, as monitored by microdialysis.

Lesions of the fimbria-fornix pathways are known to induce a partial cholinergic and noradrenergic denervation of the hippocampal formation, which is followed by a slow and protracted collateral sprouting by the spared afferents. Using the intracerebral microdialysis technique, compensatory changes in extracellular levels of acetylcholine (ACh) and noradrenaline (NA) have been monitored over time in the partially denervated hippocampus of awake unrestrained rats subjected to an unilateral fimbria-fornix (FF) transection. One week after the lesion, baseline ACh output was reduced by 90% and 80% in the dorsal and ventral hippocampus, respectively, and it remained depressed still by 6 months after lesion. KCl-evoked and atropine-stimulated ACh efflux were equally reduced by 1 week after lesion, remained depressed at 3 months, but showed a significant recovery by 6 months post-lesion. Tissue choline acetyltransferase (ChAT) activity levels, initially reduced by 92% and 86%, in the dorsal and ventral hippocampus, respectively, recovered significantly by 3 months and remained unchanged at 6 months. Baseline NA output was significantly reduced (-80%) in the dorsal hippocampus by 1 week after the lesion and showed a partial recovery over time (to 50% of normal), whereas the ventral part was not significantly affected by the FF lesion. The significant FF lesion-induced reduction in KCl- or desipramine (DMI)-stimulated NA release observed in the dorsal hippocampus at 1 week after the lesion remained unchanged during the subsequent months. By contrast, in the ventral hippocampus, the initial 65-70% reduction in KCl- and DMI-stimulated NA release significantly recovered to normal levels within 3 months post-lesion. The NA tissue levels were significantly reduced by 4 weeks after lesion, in the dorsal hippocampus and did not show any significant recovery over time. In the ventral hippocampus, these levels were significantly reduced only at 4 weeks. Transmitter turnover, expressed as the ratio between dialysate levels and tissue ChAT or NA content, showed a 3-fold increase in the dorsal hippocampus at 4 weeks after lesion, but not at later time points. This indicates that the spared noradrenergic and cholinergic afferents respond to the partial denervation by a transient increase in transmitter turnover, evident as early as 4 weeks post-lesion in the region of maximal denervation. This was followed by a long-term increase in evoked transmitter release which may result from a slowly progressing compensatory sprouting of the spared afferents.

Acetylcholine↗
PubMed1993

Regulation of neurotrophin and trkA, trkB and trkC tyrosine kinase receptor messenger RNA expression in kindling.

Levels of messenger RNA for nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, and the tyrosine kinase receptors trkA, trkB and trkC have been studied using in situ hybridization in the rat brain 2 h and four weeks after kindling-induced seizures. Epileptiform activity evoked by hippocampal stimulation and exceeding 70 s lead to a concomitant and transient increase of brain- derived neurotrophic factor, nerve growth factor, trkB and trkC messenger RNA expression in dentate granule cells after both focal and generalized seizures. Brain-derived neurotrophic factor messenger RNA levels were also increased bilaterally in the CA1-CA3 regions, amygdala and the piriform, entorhinal, perirhinal, retrosplenial and temporal cortices after generalized seizures. The magnitude of the increases was similar throughout the development of kindling and in the fully kindled brain. No changes of trkA messenger RNA were observed. In amygdalar kindling, elevated brain-derived neurotrophic factor messenger RNA levels developed more rapidly in the amygdala-piriform cortex than after stimulation in the hippocampus but changes in the hippocampal formation were only seen in few animals. Intraventricular 6-hydroxydopamine or a bilateral fimbria-fornix lesion did not alter basal expression or seizure-evoked changes in messenger RNA levels for neurotrophins or trk receptors but increased the number of animals exhibiting elevated levels after the first stimulation, probably due to a prolongation of seizure activity. Both in sham-operated and fimbria-fornix-lesioned rats seizure activity caused a marked reduction of neurotrophin-3 messenger RNA levels in dentate granule cells. The results indicate that activation of the brain-derived neurotrophic factor gene, at least in dentate granule cells, is an "all-or-none" type of response and dependent on the duration but not the severity of seizures or the stage of kindling epileptogenesis. Changes in brain-derived neurotrophic factor, nerve growth factor, neurotrophin-3 and trkB and trkC were observed concomitantly in the dentate gyrus, which suggests that seizure activity sets in motion a cascade of genomic events possibly mediated via a common mechanism. Since altered messenger RNA levels outside hippocampus were detected only for brain-derived neurotrophic factor, neurotrophin and trk gene expression in these regions seems to be regulated differently.

Amygdala↗
PubMed1992

Acetylcholine release in the hippocampus: regulation by monoaminergic afferents as assessed by in vivo microdialysis.

The role of monoamines in the functional regulation of the septo-hippocampal cholinergic system was studied using in vivo microdialysis of acetylcholine (ACh) release in the hippocampus of awake unrestrained rats. Systemic administration of the dopamine receptor agonist apomorphine (2.0 mg/kg) resulted in a 170% increase in hippocampal ACh overflow. Similarly the catecholamine-releasing agent amphetamine (2.5 mg/kg) produced a 400% increase in ACh overflow. The effect induced by amphetamine, but not that of apomorphine, was blocked in animals pretreated with the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine (AMPT). The effect of amphetamine on ACh release was reduced by 75% after a 6-hydroxydopamine (6-OHDA) lesion of the ventral tegmental area (VTA) but was not affected by 6-OHDA lesions of the noradrenergic dorsal and ventral bundles. However, baseline ACh overflow was increased by 130% by the dorsal and ventral bundle lesions. The serotonin-releasing agent p-chloroamphetamine (2.5 mg/kg) produced a 160% increase in hippocampal ACh release, and this effect was enhanced after a 5,7-dihydroxytryptamine (5,7-DHT) lesion of the serotonin projection system. The results show that surgical or pharmacological manipulations of the ascending brainstem monoaminergic systems, which innervate wide areas of the forebrain, including the septum and the hippocampal formation, have pronounced effects on septo-hippocampal cholinergic activity. Thus, the present data provide support for the view that information regarding behavioral state and arousal is conveyed to the septo-hippocampal system via ascending monoaminergic systems.

5,7-Dihydroxytryptamine↗
PubMed1992

Spatial learning impairments in rats with selective immunolesion of the forebrain cholinergic system.

A monoclonal antibody to the low-affinity NGF receptor, 192 IgG, coupled to a cytotoxin, saporin, was recently introduced as an efficient selective neurotoxin for the NGFr-bearing cholinergic neurones in the rat basal forebrain. In the present study we report that an intracerebroventricular injection of this 192 IgG-saporin conjugate induces a severe, long-lasting spatial learning impairment, as assessed in the Morris water-maze task. This behavioural impairment was associated with 65-90% depletion of choline acetyltransferase activity (ChAT) in the hippocampus and cortex. ChAT activity associated with other cholinergic neurone systems in the brain (striatum, mesencephalon, spinal cord), was left virtually unaffected. This new immunotoxin holds great promise as a tool for selective and efficient lesions of the forebrain cholinergic system in functional and behavioural studies.

Acetylcholinesterase↗
PubMed1991

Neurons in raphe nuclei pontis and magnus have branching axons that project to medial preoptic area and cervical spinal cord. A fluorescent retrograde double labeling study in the rat.

In this study, we utilized a double retrograde axonal tracing technique to investigate the possible existence of collateralized axonal projections from raphe nuclei 'pontis' and 'magnus' to both medial preoptic area (MPA) and cervical spinal cord (C1-C2). Following microinjections of fluorescent tracers Fast blue (FB) and Diamidino yellow (DY) within MPA and C1-C2, substantial numbers of FB and DY single-labeled neurons, as well as FB-DY double-labeled neurons have been found within raphe nuclei 'pontis' and 'magnus'.

Amidines↗
PubMed1989

Branching projections from subcoeruleus area neurons to medial preoptic area and cervical spinal cord revealed by double retrograde neuronal labeling.

In this study we utilized a double retrograde axonal tracing technique to investigate the possible existence of collateralized axonal projections of subcoeruleus area neurons to both 'medial preoptic area (MPA) and cervical (C1-C3) spinal cord'. Following microinjections of fluorescent tracers (Fast blue (FB) and Diamidino yellow (DY) within MPA and C1-C3, substantial numbers of FB and DY single-labeled neurons as well as FB-DY double-labeled branched neurons have been found within subcoeruleus area.

Amidines↗
PubMed1988

Role of the ventromedial hypothalamus in the regulation of adenohypophyseal immunoreactive dynorphin in the rat.

In this study, we have examined the role of the dorsomedial (DMH), ventromedial (VMH) and arcuate (ARH) nuclei of the hypothalamus in the control of hypothalamic and pituitary immunoreactive (ir) dynorphin (Dyn) A and ir-Dyn B in the rat, by evaluating the effect of discrete, bilateral radiofrequency lesions in these structures. Lesions limited to the VMH reduced the content of ir-Dyn in the anterior pituitary but not in the neurointermediate lobe or in the hypothalamus. Gel chromatographic analysis of anterior pituitary extracts confirmed that ir-Dyn is mainly associated with high molecular weight forms containing Dyn A and Dyn B in their sequence. Anterior pituitary extracts of VMH-lesioned rats displayed a clearly lower proportion of these forms. Destruction of the DMH affected only the hypothalamic content of ir-Dyn; ablation of the ARH did not cause any significant change. Our results suggest that ablation of the VMH may disrupt critical neuronal connections to the median eminence originating in this nucleus or crossing it and participating in control of the adenohypophyseal pool of ir-Dyn.

Animals↗
PubMed1988

Branching axons from subcoeruleus area project to the nucleus raphe pontis and hypothalamic zona incerta, as studied with the double fluorescent retrograde tracing technique.

In this study we utilized a double retrograde axonal tracing technique to investigate the possible existence of collateralized axonal projections of subcoeruleus area neurons to both raphe pontis nucleus and hypothalamic zona incerta. Following microinjections of fluorescent tracers (Fast blue (FB) and Diamidino yellow (DY] within raphe pontis and zone incerta, substantial numbers of double-labeled branched neurons have been found within the subcoeruleus area.

Amidines↗
PubMed1986

Immunoreactive dynorphin-like material in rat pituitary after ovariectomy.

Ovariectomy caused a significant increase of immunoreactive dynorphin-like material (IR-DYAN) in the anterior pituitary lobe of intact as well as of medial basal hypothalamus-lesioned rats. No change of IR-DYAN was observed in the neurointermediate lobe of the gland or in the hypothalamus. Estradiol benzoate reversed the increase of anterior pituitary IR-DYAN induced by ovariectomy and caused a reduction in sham-ovariectomized rats.

Animals↗
PubMed1984

[Projections to the supraoptic and paraventricular nuclei studied in the rat by means of retrograde fluorescent tracers (fast blue, nuclear yellow)].

Afferent projections into rat supraoptic nucleus (SO) and paraventricular nucleus (PVH) were studied with two fluorescent retrograde neuronal tracers: Nuclear Yellow (NY) and Fast Blue (FB). FB labeled cells were found into paraolfactory area (ACB), basolateral amygdaloid nucleus (ABL), lateral hypothalamus (LH), ventromedial nucleus (VMH) and dorsomedial hypothalamic)nucleus (DMH), tegmental nucleus of the pons (TPO). NY labeled cells were found into posterior hypothalamus (PH), dorsal raphe nucleus (DR) and tegmental nucleus of the pons (TPO). Few double-labeled neurons were found into TPO. The finding of double labeled neurons in the TPO is of particular interest. This latter nucleus is classically connected to the cerebellum trough the olivary nucleus and can serve as liaison for transmission of messages, e.g. vestibular, regarding spacial position variations. We can conclude affirming that quite a lot of informations of diverse nature converges on the SO and PVH nuclei that by efferent pathways may regulate hypothalamic neurosecretion, thus modifying the animal's behaviour response to different external stimuli.

Afferent Pathways↗