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PubMedDate not supplied

CCK-A and CCK-B receptors enhance olfactory recognition via distinct neuronal pathways.

We have previously reported that CCK-A receptor agonists and CCK-B receptor antagonists both enhance memory in an olfactory recognition test. Here, we report that the memory-enhancing effect of the CCK-B receptor antagonist L-365,260 (1 mg/kg i.p.), but not that of the CCK-A receptor agonist caerulein (0.03 mg/kg i.p.), was dramatically decreased following a bilateral transection of the perforant path, a principal source of input to the hippocampal formation. We further confirmed that a significant memory deficit occurred subsequent to this deafferentation of the hippocampus in untreated animals. In contrast, the effect of caerulein, but not that of L-365,260, was abolished following a bilateral subdiaphragmatic vagotomy. These results demonstrate that the hippocampal system plays a role in olfactory recognition and indicate that distinct neuronal pathways underlie the memory-enhancing effects of CCK-A and CCK-B drugs observed in the olfactory recognition test. The former effects (CCK-A) appear to involve a peripheral relay to the brain via the vagus nerve, whereas the latter (CCK-B) are directly central and involve, at least in part, the hippocampal system.

Animals↗
PubMed1994

Role of envelope glycoproteins gI, gp63 and gIII in the invasion and spread of Aujeszky's disease virus in the olfactory nervous pathway of the pig.

One-week-old pigs were infected intranasally with the Ka strain of Aujeszky's disease virus (ADV) or with mutants that were lacking the non-essential envelope glycoproteins gI, gp63 or gIII. The invasion and spread of these strains in the olfactory nervous pathway were examined by assessing virus levels and by localizing viral antigens in the olfactory mucosa representing the first neuronal level, in the olfactory bulb representing the second neuronal level and in the lateral olfactory gyrus, the rostral perforated substance and the piriform lobe, all representing the third neuronal level. The Ka parental strain invaded and spread up to the third neuronal level. The extent of invasion and spread of the gIII- mutant were similar to those of the parental strain. The gp63- mutant replicated normally in the olfactory mucosa, but its spread to all the other levels was limited as compared with that of the parental strain. The gI- mutant showed a defect in infection at all neuronal levels. These results indicate that, of the non-essential envelope glycoproteins, gI plays the major role in neural invasion and spread of ADV in its natural host. The pattern of invasion and spread of these mutants in the olfactory pathway of pigs was similar to that previously observed in the trigeminal pathway. The type of nervous pathway therefore appears not to influence the neuropathogenesis of ADV or mutants deleted in non-essential envelope glycoproteins in the pig.

Animals↗
PubMed1994

Increase in synaptic vesicle proteins accompanies long-term potentiation in the dentate gyrus.

Maintenance of long-term potentiation in synapses formed by the perforant path on to granule cells of the dentate gyrus is accompanied by a sustained increase in the extracellular concentration of glutamate, the presumed transmitter at this excitatory hippocampal pathway. Quantal analysis indicates that, at least in the first hour of induction, this reflects an increase in transmitter release rather than a decrease in glutamate uptake, while biochemical studies have suggested that the increase in release persists for several hours. Morphological studies have described early but persistent increases in the spine number and area. Increases in the number of segmented/perforated synapses persisting for at least 1 h after induction of long-term potentiation, have also been reported. These morphological changes suggest both presynaptic and postsynaptic modifications. Increases in synaptic vesicle number and distribution lasting for at least 1 h specifically indicate presynaptic changes. To explore further the role of the presynaptic terminal in long-term potentiation, we have investigated changes in three synaptic vesicle proteins, synapsin, synaptotagmin and synaptophysin, in control tissue and in tissue prepared from potentiated dentate gyrus 45 min and 3 h after induction of long-term potentiation. We found that there was an increase in the concentration of the three proteins 3 h after induction of long-term potentiation. No such increase was observed 45 min after induction or in tissue prepared from animals in which an intraventricular injection of the N-methyl-D-aspartate receptor antagonist, D(-)-2-amino-5-phosphonopentanoic acid, blocked induction of long-term potentiation.

2-Amino-5-phosphonovalerate↗
PubMed2001

Deep sclerectomy with a collagen implant using the excimer laser.

We describe a new technique of nonpenetrating glaucoma surgery that uses the excimer laser to reduce the risk of perforating the trabeculo-Descemet's membrane. With this technique, the ablation is precise and homogeneous. A collagen device is sutured over the scleral bed to create an outflow pathway for aqueous humor drainage. After a superficial scleral flap is dissected with a diamond knife, the sclera, under direct visualization, is ablated with the excimer laser over Schlemm's canal until aqueous humor percolates through from the anterior chamber. A collagen device is placed over the sclera to allow the aqueous humor to flow from the anterior chamber through the trabeculo-Descemet's membrane. The preliminary results show a drop in intraocular pressure to the middle teens.

Aqueous Humor↗
PubMed1996

Sources and sites of action of calcium in the regulation of aldosterone biosynthesis.

The role of free calcium as a crucial intracellular messenger in the stimulation of aldosterone biosynthesis by various agonists is well established. Using electropermeabilized or Ca(2+)-clamped adrenal zona glomerulosa (ZG) cells, we have previously shown that Ca2+ entry into the mitochondrial matrix is required for the activation of steroidogenesis. We now describe the use of various strategies to answer the following questions: 1. Which pathway does Ca2+ follow before triggering steroidogenesis? 2. Which step of steroidogenesis is under the control of Ca2+? The first approach combined the patch-clamp method, in the perforated patch configuration, with microfluorimetry of Ca2+; in the second approach, ZG cells were transiently transfected with a chimeric cDNA encoding for the calcium-sensitive photoprotein aequorin linked to a mitochondrial targeting presequence; in a third approach, ZG mitochondria were isolated and fractionated into outer membranes, contact sites and inner membranes and the effect of prior exposure of the ZG cells to a physiologically elevated intracellular calcium concentration or to angiotensin II (Ang II) on cholesterol content was then examined in those three mitochondrial fractions. The results of these combined approaches allow us to propose the following scheme: The source of calcium which is predominantly responsible for mediating the steroidogenic effect of potassium appears to be funneled through the T-type calcium channels to close proximity of the mitochondria. This signal, as well as that triggered by Ang II, appears to be relayed within the mitochondrial matrix. This rise of mitochondrial calcium is associated with a transfer of free cholesterol from the outer to the inner mitochondrial membrane, via the contact sites. Thus the main role of the calcium messenger is to promote intramitochondrial cholesterol transfer and supply to the P450scc enzyme.

Aequorin↗
PubMed1991

The effects of serotonin depletion and raphe grafts on hippocampal electrophysiology and behavior.

The involvement of the serotonergic system in spatial learning and a possible correlation between serotonergic modulation of hippocampal electrical activity and spatial learning were studied in rats. Control, partial septal-lesioned (SL), 5,7-dihydroxytryptamine (5,7-DHT)-injected (DHT), double-lesioned (5,7-DHT and SL; DL), and DL rats that were transplanted with embryonic raphe grafts into the hippocampus (RG) were tested in a spatial task in a water maze and in an active avoidance shuttle-box task. The responses of the dentate gyrus (DG) to perforant-path (PP) stimulation were examined in the same rats, under the following conditions: (1) priming stimulation of the PP (testing feedback inhibition), (2) priming stimulation of the commissural pathway (testing feedforward inhibition), (3) during repeated stimulation of the PP at 7 Hz (frequency potentiation), and (4) following tetanic stimulation [long-term potentiation (LTP)]. DL, but not DHT or SL, treatment severely impaired the performance of rats in both reference- and working-memory tasks in the water maze. This effect was not seen in the shuttle box. The ability of the DG to exhibit LTP, which was reduced in the DHT and SL rats, was apparently similar to controls in the DL group, DL, but not DHT or SL alone, resulted in a reduction of inhibition in the DG. Both the behavioral deficits and the reduction in hippocampal inhibition were ameliorated by intrahippocampal raphe grafts. These results indicate that the serotonergic innervation of the hippocampus plays a role in spatial learning when the septohippocampal neurotransmission systems are disrupted. Furthermore, these results suggest that restoration of modulation of hippocampal inhibition, by raphe grafts, underlies the behavioral recovery observed in these rats.

5,7-Dihydroxytryptamine↗
PubMed1988

[Experimental study of brain stem infarction in dogs--effect on BAEP, SSEP, blink reflex and EEG of perforator occlusion].

Assessment of the lesion in the brain stem by evoked potentials has not been well established. We have already developed a model of brain stem ischemia by occluding the perforators of the posterior cerebral arteries of the dog. The ischemic lesions locates mainly in the ventral side of the midbrain. Using this model, we assessed brain stem function by brain stem auditory evoked potential (BAEP), surface- and depth-recorded (in medial lemniscus) short latency somatosensory evoked potential (SSEP), blink reflex (BR) and electroencephalography (EEG), and investigated the correlation between the electrophysiological abnormalities and the lesion in the brain stem. The studies were performed for 6 hours after perforator occlusion. Furthermore, depth-recorded SSEP and regional cerebral blood flow (rCBF) were measured under induced hypotension by withdrawal of arterial blood. BAEP did not change in 13 of 16 animals. Surface-recorded SSEP remained unchanged in all 6 animals. The results are probably due to the fact that the lesion does not involve the auditory and somatosensory pathways and the accompanying events such as edema does not affect the both pathways. Depth-recorded SSEP remained unchanged after occlusion and did not disappear even when rCBF fell below 10 ml/100 g/min. It may be suggested that the threshold for electrical failure in the brain stem is much lower than that in the cortex. In BR, R1 did not change but ipsilateral R2 became nearly invisible immediately after perforator occlusion in all animals. The fact that the ischemic lesion did not involve the pons and disturbed reticular formation in the midbrain may probably account for the remaining of R1 and the disappearance of ipsilateral R2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2001

Plasticity of afferent fibers to striatal neurons bearing D1 dopamine receptors in Parkinson's disease.

The loss of dopaminergic neurons in the substantia nigra provokes a plasticity of corticostriatal synapses in Parkinson's disease (PD). The corticostriatal pathway nevertheless makes synapses with neurons bearing D1 dopamine receptors (D1R) and/or D2 dopamine receptors. At the ultrastructural level, we analyzed the morphological characteristics of synapses formed by afferent fibers making asymmetric contacts with the dendritic spines of neurons identified by D1R immunoreactivity, in the striatum of control subjects and PD patients. A quantitative analysis of the morphological characteristics of the synapses and of the number of perforated synapses (considered to be very active) was performed. In PD, a 50% increase in the number of perforated synapses making contact with D1R dendritic spines was observed, whereas no change in the number of perforated synapses on non-D1R spines was observed. The change in the number of perforated synapses on D1R dendrites was associated with a slight but nonsignificant increase in the surface area of the corticostriatal afferent fibers and the surface of the mitochondria in these fibers (+29.0% and +34.6%, respectively). This suggests a hyperactivity of corticostriatal fibers in contact with D1R-bearing neurons of the direct pathway in the basal ganglia circuitry. Since stimulation of the direct pathway is thought to alleviate the clinical symptoms of PD, this suggests that the differences observed may be involved in compensatory mechanisms.

Aged↗
PubMed2000

Amplification of odor-induced Ca(2+) transients by store-operated Ca(2+) release and its role in olfactory signal transduction.

A critical role of Ca(2+) in vertebrate olfactory receptor neurons (ORNs) is to couple odor-induced excitation to intracellular feedback pathways that are responsible for the regulation of the sensitivity of the sense of smell, but the role of intracellular Ca(2+) stores in this process remains unclear. Using confocal Ca(2+) imaging and perforated patch recording, we show that salamander ORNs contain a releasable pool of Ca(2+) that can be discharged at rest by the SERCA inhibitor thapsigargin and the ryanodine receptor agonist caffeine. The Ca(2+) stores are spatially restricted; emptying produces compartmentalized Ca(2+) release and capacitative-like Ca(2+) entry in the dendrite and soma but not in the cilia, the site of odor transduction. We deplete the stores to show that odor stimulation causes store-dependent Ca(2+) mobilization. This odor-induced Ca(2+) release does not seem to be necessary for generation of an immediate electrophysiological response, nor does it contribute significantly to the Ca(2+) transients in the olfactory cilia. Rather, it is important for amplifying the magnitude and duration of Ca(2+) transients in the dendrite and soma and is thus necessary for the spread of an odor-induced Ca(2+) wave from the cilia to the soma. We show that this amplification process depends on Ca(2+)-induced Ca(2+) release. The results indicate that stimulation of ORNs with odorants can produce Ca(2+) mobilization from intracellular stores without an immediate effect on the receptor potential. Odor-induced, store-dependent Ca(2+) mobilization may be part of a feedback pathway by which information is transferred from the distal dendrite of an ORN to its soma.

Animals↗
PubMed1981

Correlation of foot arterial anatomy with early tibial bypass patency.

The detailed arterial anatomy of the foot in severe limb ischemia is not well known. This study was undertaken to define foot arterial anatomy and correlate these findings with the early results (6 months) of femoral-distal bypass. After completion of the bypass, operative arteriography was performed by direct injection of contrast media into the graft. A lateral view of the distal limb and foot was obtained. Foot vessel anatomy was classified into primary and secondary pedal arches, analogous to the superficial and deep volar arches of the hand. For peroneal bypass, special attention was paid to perforating branches and their communications with these two pedal arches. A total of 56 distal bypass operations was analyzed. Femoral--anterior tibial bypass was performed in 26 cases. When either a primary or a secondary pedal arch was intact, early graft patency (6 months) was achieved in 20 of 21 patients. When neither pathway was present, graft failure occurred in four of five cases. Similarly, of 10 femoral--posterior tibial grafts, seven remained patent with at least one pedal arch intact, whereas six of seven grafts failed when neither arch was patent. Bypass to the peroneal artery was successful in eight of nine limbs when a patent primary or secondary arch was reconstituted via either the anterior or posterior perforating branches. None of four peroneal grafts remained patent when both arches were occluded. As a whole, in 40 limbs with either a patent primary or secondary pedal arch, early graft success was achieved in 35 limbs (87.5%). In contrast, in 16 limbs with no patent arch, only two (12.5%) were successfully reconstructed (P less than 0.001). Analysis of the results of femoral-distal bypass based on a single plantar arch as the sole determining anatomic factor in graft patency is not adequate. The secondary pedal arch and communicating branches of the peroneal artery are also of surgical significance. Operative arteriography can define runoff in the foot, and this information has prognostic significance. It may allow rational judgment regarding reintervention in patients with failed grafts.

Adult↗
PubMed1989

Laser-assisted thermal angioplasty in human peripheral artery occlusions: mechanism of recanalization.

Recanalization of completely occluded superficial femoral or popliteal arteries was attempted in 18 patients with use of an Argon laser-mediated thermal probe. The length of the occluded segments varied between 0.5 and 26.0 cm, but 67% of the occlusions were greater than 9 cm long. The initial success rate was 67%. Arterial perforation occurred in six patients but was not associated with major complications. To study the mechanism of the laser-mediated thermal probe, thermal recanalization was performed on 11 human arterial segments in vitro obtained after amputation, and mechanical recanalization was performed in vitro in 10 human peripheral arteries with use of a guide wire and catheter technique. An additional four arteries were studied with the laser probe as a non-heated mechanical device. Both the mechanical and thermal devices appear to follow a similar pathway through a complete obstruction. These studies suggest that the thermal probe burns through soft fibrous tissue but is mechanically deflected away from hard fibrocalcific plaque. The probe then advances along the plane between the intimal plaque and the media for a variable length before perforating through the adventitia. These observations suggest that the major mechanism of thermal probe recanalization may be a mechanical process. It appears that thermal probe devices do not inherently seek the true lumen of an occluded artery and that better guidance systems need to be developed.

Aged↗
PubMed1991

Mossy fiber synaptic reorganization induced by kindling: time course of development, progression, and permanence.

Recent studies have revealed that mossy fiber axons of granule cells in the dentate gyrus undergo reorganization of their terminal projections in both animal models of epilepsy and human epilepsy. This synaptic reorganization has been demonstrated by the Timm method, a histochemical technique that selectively labels synaptic terminals of mossy fibers because of their high zinc content. It has been generally presumed that the reorganization of the terminal projections of the mossy fiber pathway is a consequence of axonal sprouting and synaptogenesis by mossy fibers. To evaluate this possibility further, the time course for development of Timm granules, which correspond ultrastructurally to mossy fiber synaptic terminals, was examined in the supragranular layer of the dentate gyrus at the initiation of kindling stimulation with an improved scoring method for assessment of alterations in Timm histochemistry. The progression and permanence of this histological alteration were similarly evaluated during the behavioral and electrographic evolution of kindling evoked by perforant path, amygdala, or olfactory bulb stimulation. Mossy fiber synaptic terminals developed in the supragranular region of the dentate gyrus by 4 d after initiation of kindling stimulation in a time course compatible with axon sprouting. The induced alterations in the terminal projections of the mossy fiber pathway progressed with the evolution of behavioral kindled seizures, became permanent in parallel with the development of longlasting susceptibility to evoked seizures, and were observed as long as 8 months after the last evoked kindled seizure. The results demonstrated a strong correlation between mossy fiber synaptic reorganization and the development, progression, and permanence of the kindling phenomenon.

Amygdala↗
PubMed2005

Aerenchyma tissue development and gas-pathway structure in root of Avicennia marina (Forsk.) Vierh.

The aerenchyma differentiation in cable roots, pneumatophores, anchor roots, and feeding roots of the mangrove plant, Avicennia marina (Verbenaceae) was analyzed using a light microscope and scanning electron microscope. In all types, cortex cells were arranged in longitudinal columns extending from the endodermis to the epidermis. No cells in the cortex had intercellular spaces at the root tip (0-150 microm), and aerenchyma started developing at 200 microm from the root apex. The aerenchyma formation was due to cell separation (schizogeny) rather than cell lysis. The cell separation occurred between the longitudinal cell columns, forming long intercellular spaces along the root axis. During aerenchyma formation, the cortex cells enlarged longitudinally by 1.8-3.9 times and widened horizontally by 2.2-2.9 times. As a result, the aerenchyma had a pronounced tubular structure that was radially long, elliptical or oval in cross section and that ran parallel to the root axis. The tube had tapering ends, as did vessel elements, although there were no perforated plates. The interconnection between neighboring tubes was made by abundant small pores or canals that were schizogenous intercellular spaces between the wall cells. All aerenchyma tubes in the root were interconnected by these small pores serving as a gas pathway.

Gases↗
PubMed2006

[Pathophysiology and pathomorphology of osteoporosis].

Osteoporosis is a disease that leads to fragility fractures due to loss of bone mass and bone microstructure. This review presents an update on the fundamental pathophysiologic and pathomorphologic mechanisms of bone loss situations. Pathomorphologic characteristics such as perforations and microcallus formations are explained. The physiologic relevance of the remodeling process as well as its control by local-paracrine, systemic-endocrine and central-neural signaling pathways is discussed. Furthermore the role of hormones such as estrogen, FSH and leptin, of transcription-factors such as Runx2 and osterix and as well as that of the wnt signaling pathway for bone cell differentiation and function is presented. On the basis of current knowledge osteoporosis can be diagnosed, treated and fractures can be prevented. However, it is likely that new and even more effective diagnostic and therapeutic strategies will emerge as our understanding of the remodeling process that controls osteoblast and osteoclast function increases.

Bone Resorption↗
PubMed1992

[Non traumatic acute suppurative mediastinitis].

Acute mediastinitis is uncommon. When it occurs, it usually follows an esophageal perforation or thoracic surgery. We report on a case of a 2-year-old girl with non traumatic mediastinitis secondary to a pharyngitis, due to Staphylococcus aureus. The anatomic pathways that connect the cervical region with the mediastinum explains how the infection can spread within the cervicothoracic spaces. Knowledge of this anatomy is also important in evaluating the possible causes of symptoms and signs in this area, and the possible complications of infections in these regions. The treatment associates antibiotics and drainage of the abscess by either surgical procedure or computed tomography guided selective needle aspirations.

Acute Disease↗
PubMed2004

Olfactory transduction in ciliated receptor neurons of the Cabinza grunt, Isacia conceptionis (Teleostei: Haemulidae).

The ciliated receptor neurons of fish olfactory organs are thought to transduce amino acids through a cAMP-dependent transduction pathway, but direct physiological evidence for this hypothesis remains scarce and is confined to catfish and trout. We investigated olfactory transduction in a marine fish, the Cabinza grunt Isacia conceptionis (Perciformes, Teleostei). The olfactory epithelium was characterized using light and electron microscopy, and isolated ciliated receptor neurons were recorded with the perforated patch-clamp technique. Cells were stimulated with puffer pipettes containing amino acid odourants, IBMX plus forskolin or 8 bromo-cAMP. All three stimuli triggered transient inward currents at a holding potential of -70 mV and responses with outward-rectifying current-voltage relationships. The characteristics of the transduction currents induced by each stimulus were similar across cells and indistinguishable within the same cell, supporting the hypothesis of a cAMP pathway mediating transduction of amino acids in ciliated olfactory receptor neurons.

1-Methyl-3-isobutylxanthine↗
PubMed1996

The regulation of hippocampal dynorphin by neural/neuroendocrine pathways: models for effects of aging on an opioid peptide system.

Previous research has demonstrated increased messenger RNA expression and peptide content in an opioid system localized to hippocampal dentate granule cells in aged rats. This altered regulation of dynorphin was correlated with the emergence of an age-related impairment in spatial learning. Considerable evidence exists for additional effects of aging on systems that provide input to the dynorphin-containing dentate granule cells. Such changes have been well documented for loss of perforant path innervation from entorhinal cortex, deterioration in septohippocampal cholinergic neurons, and high amounts of glucocorticoids that have, among their targets, receptors located in the dentate gyrus. Similar to the effects of aging on hippocampal dynorphin, age-related changes in each of these systems correlate with the severity of spatial learning impairment in aged rats. This raises the possibility that dysregulation of dynorphin in the aged brain is a reactive response to antecedant change(s) in this circuitry, a hypothesis that was examined by separately manipulating in young rats the three neural/neuroendocrine systems identified above. Of the three models examined only removal of the perforant path reproduced the effect of aging on dynorphin in the hippocampal formation. An immunotoxin was used in Experiment 1 to selectively remove septo-hippocampal cholinergic neurons in young rats. No alteration in hippocampal opioid peptides was produced by this treatment. Experiment 2 examined effects of exposure to excess corticosterone. Adrenalectomized rats exhibited a significant decrease in hippocampal dynorphin-A (1-8) content, which was reversed by corticosterone replacement at a concentration approximating normal basal levels. Dynorphin-A (1-8) content, however, was not reliably increased by exposure to excess corticosterone. In contrast, perforant path removal was found to reproduce the effect of aging on dynorphin content; either aspiration of the entorhinal cortex or knife-cut transections of the perforant path reliably increased hippocampal dynorphin content. These results support the conclusion that age-related deterioration in the septohippocampal cholinergic system and evaluated exposure to corticosterone are not sufficient to induce an elevation in hippocampal dynorphin content. Only removal of the perforant path innervation was found to reproduce the elevation in hippocampal dynorphin content observed in aged rats with hippocampal-dependent learning impairment.

Adrenalectomy↗