jacques callebert

In the present study, using the microdialysis technique, we provided evidence of the existence of hydroxyl radicals (·OH) in the striatum of awake rats under physiological conditions. This ·OH generation was virtually abolished by the N-methyl-d-aspartate (NMDA) receptor antagonist dizocilpine. On the contrary, it was significantly enhanced by the ·NO synthase inhibitor NG-nitro-d-arginine methyl ester (l-NAME). The effect of l-NAME was completely reversed by l-arginine. These results suggest that the basal ·OH production is largely the consequence of an NMDA receptor-mediated glutamatergic tone. Moreover, it is likely that endogenous ·NO exerts an antioxidant activity in brain by preventing the rise in ·OH levels.

ABSTRACT Supporting the hypothesis that proteasome dysfunction is involved in Parkinson's disease (PD), McNaught et al. (2004) reported that the systemic administration of the proteasome inhibitor Z-Ile-Glu(OtBu)-Ala-Leu-aldehyde (PSI) in rats led to the degeneration of the nigrostriatal pathway. However, several groups could not reproduce this finding. We herein attempted to improve the reliability of the PSI model by chronically delivering the inhibitor using osmotic minipumps in aged mice. We also tested whether PSI co-administered with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) could act synergistically to induce toxicity. We found that PSI produced a significant reduction in locomotor activity that was mildly exacerbated by MPTP. However, PSI alone produced no sign of degeneration of the nigrostriatal dopaminergic pathway and did not exacerbate MPTP toxicity. To conclude, PSI administration does not provide a reliable phenotypic model of PD.

The loss of dopaminergic neurons in Parkinson's disease is associated with a glial reaction and the overproduction of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-α). TNF-α acts via two different receptors, TNFR1 and TNFR2, and is believed to have both a neuroprotective and a deleterious role for neurons. In order to analyze the putative role of TNF-α in parkinsonism, we compared the effect of the parkinsonian drug 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice lacking TNFR1, TNFR2, or both receptors and in wild-type littermates. We show that MPTP does not affect spontaneous activity or anxiety in any of the groups and that it reduces motor activity on a rotarod in double knock out mice but not in mice lacking only one receptor. Postmortem analysis revealed no differences in the number of nigral dopaminergic neurons whatever the group. In contrast, striatal dopamine level was slightly decreased in double knock-out mice and more reduced by MPTP in this group than in the other groups of mice. In addition, dopamine turnover was significantly more increased in double knock out mice after MPTP injection. These data suggest that TNF-α does not participate in the death of dopaminergic neurons in parkinsonism but that it slightly alters dopamine metabolism or the survival of dopaminergic terminals by a mechanism involving both receptors.

Background: Autism is known to be associated with hyperserotoninemia and, more recently, with decreased blood melatonin level. Melatonin is a neurohormone synthesized from serotonin and involved in circadian rhythms and sleep regulations. Thus, serotonin and melatonin are two ends of a biochemical pathway, and little is known concerning all the steps of this pathway in patients with Autism Spectrum Disorders. Moreover, the clinical relevance of these biochemical endophenotypes remains to be determined. Objectives: Here we explore the serotonin-melatonin pathway in a large cohort of patients with ASD, in order to (i) better characterize the biochemical abnormalities of this pathway in ASD, (ii) determine the clinical correlates of these biochemical abnormalities, and (iii) assess the relevance of these biochemical parameters as biomarkers for ASD diagnosis. Methods: The five parameters related to the serotonin-melatonin pathway, i.e. serotonin, arylalkylamine N-acetyltransferase (AA-...

PHYSICIANS ABSTRACTSO1 Impact of tracheal cuff shape on microaspiration of gastric contents in intubated critically ill patients: a multicenter randomized controlled study (BEST CUFF)Emmanuelle Jaillette, Christophe Girault, Guillaume Brunin, Farid Zerimech, Arnaud Chiche, Céline Broucqsault-Dedrie, Cyril Fayolle, Franck Minacori, Isabelle Alves, Stephanie Barrailler, Laurent Robriquet, Fabienne Tamion, Emmanuel Delaporte, Damien Thellier, Claire Delcourte, Alain Duhamel, Saad NseirO2 Bicarbonate versus saline for contrast-induced acute kidney injury prevention in critically ill patientsXavier Valette, Isabelle Desmeulles, Benoit Savary, Romain Masson, Amélie Seguin, Cédric Daubin, Bertrand Sauneuf, Jennifer Brunet, Pierre Verrier, Véronique Pottier, Marie Orabona, Désiré Samba, Gérald Viquesnel, Mathilde Lermuzeaux, Pascal Hazera, Jean-Luc Hanouz, Jean-Jacques Parienti, Damien Du CheyronO3 Neurally adjusted ventilatory assist in the early phase of weaning from mechanical ventilation: a multicenter randomized studyAlexandre Demoule, Marc Clavel, Camille Rolland-Debord, Sébastien Perbet, Nicolas Terzi, Achille Kouatchet, Florent Wallet, Hadrien Roze, Frédéric Vargas, Claude Guérin, Jean Dellamonica, Samir Jaber, Thomas SimilowskiO4 Very high volume hemofiltration with the Cascade system in septic shock patientsJean-Pierre Quenot, Christine Binquet, Christophe Vinsonneau, Saber-Davide Barbar, Sandrine Vinault,, Valérie Deckert, Stephanie Lemaire, Ali Ait Hssain, Rémi Bruyère, Bertrand Souweine, Laurent Lagrost, Christophe AdrieO5 Effect of rapid response systems on hospital mortality, a prospective interventional study and systematic reviewBoris Jung, Aurelien Daurat, Audrey De Jong, Gérald Chanques, Martin Mahul,, Marion Monnin, Nicolas Molinari, Samir JaberO6 Beta-lactams serum concentrations in critically ill cirrhotic patients: a matched control studyOlivier Lheureux, Eric Trepo, Maya Hites, Frederic Cotton, Fleur Wolff, Rudy Surin, Jacques Créteur, Jean-Louis Vincent, Thierry Gustot, Frederique Jacobs, Fabio Silvio TacconeO7 Systematic overdosing of oxa- and cloxacillin in severe infections treated in ICU: Risk factors and side effectsMathilde Neuville, Jean-François Timsit, Najoua El-Helali, Alban Le Monnier, Eric Magalhaes, Aguila Radjou, Roland Smonig, Jean-François Soubirou, Guillaume Voiriot, Romain Sonneville, Lila Bouadma, Bruno MourvillierO8 Amikacin peak concentrations in patients receiving extracorporeal membrane oxygenation (ECMO) support: a case-control studyElodie Gélisse, Mathilde Neuville, Etienne De Montmollin, Guillaume Voiriot, Jean-François Soubirou, Roland Smonig, Aguila Radjou, Eric Magalhaes, Lila Bouadma, Bruno Mourvillier, Jean-François Timsit, Romain SonnevilleO9 A high aminoglycoside regimen associated with renal replacement therapy for the treatment of multi-drug-resistant pathogensAlexandre Brasseur, Maya Hites, Sandrine Roisin, Frederic Cotton, Jean-Louis Vincent, Daniel De Backer, Frederique Jacobs, Fabio Silvio TacconeO10 Optimization of administration of vancomycin in septic patients: a prospective randomized studyValerie Van Ruychevelt, Eric Carlier, Michael Piagnerelli, Michel Vanhaeverbeek, Christine Danguy, Patrick BistonO11 Impact of elevated intra-abdominal pressure on the ability of dynamic parameters to predict fluid responsivenessSiu-Ming Au, Emmanuelle Begot, François Dalmay, Xavier Repessé, Gwenael Prat, Koceila Bouferrache, Michel Slama, Philippe Vignon, Antoine Vieillard-BaronO12 Passive leg raising for predicting fluid responsiveness: a systematic review and meta-analysisXavier Monnet, Paul Marik, Jean-Louis TeboulO13 Predicting volume responsiveness by using combined end-expiratory and end-inspiratory occlusion tests with echocardiographyMathieu Jozwiak, Jean-Louis Teboul, Christian Richard, Xavier MonnetO14 Early dynamic left intraventricular obstruction is associated with hypovolemia and hight mortality in septic shock patientsJean-Louis Chauvet, Shari El-Dash, Olivier Delastre, Bernard Bouffandeau, Dominique Jusserand, Jean-Baptiste Michot, Fabrice Bauer, Julien Maizel, Michel SlamaO15 Predictive factors for poor hemodynamic tolerance to fluid removal in ICU: the DepleRea studyFrançois Brazier, Pablo Mercado, Loay Kontar, Dimitri Titeca, Bertand De Cagny, Gaelle Bacari-Risal, Antoine Riviere, Michel Slama, Julien MaizelO16 High-flow nasal cannula: first-line treatment of noninvasive ventilation for infants with bronchiolitis. Applicability and risk factors for failureCamille Guillot, Claire Le Reun, Marie Lampin, Ahmed Sadik, Astrid Botte, Alain Duhamel, Stéphane LeteurtreO17 Is high-flow nasal cannula better than nasal continuous positive airway pressure for bronchiolitis management in pediatric intensive care unit?Aurélie Collins, Céline Kempeneers, Nathalie CajgfingerO18 Interest and risk of high-flow cannula during acute hypoxemic pneumonia in children: a retrospective studyCamille Ohlmann, Robin Pouyau, Fabien Subtil, Florent Baudin, Bruno…

Supporting the hypothesis that proteasome dysfunction is involved in Parkinson's disease (PD), McNaught et al. (2004) reported that the systemic administration of the proteasome inhibitor Z-Ile-Glu(OtBu)-Ala-Leu-aldehyde (PSI) in rats led to the degeneration of the nigrostriatal pathway. However, several groups could not reproduce this finding. We herein attempted to improve the reliability of the PSI model by chronically delivering the inhibitor using osmotic minipumps in aged mice. We also tested whether PSI co-administered with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) could act synergistically to induce toxicity. We found that PSI produced a significant reduction in locomotor activity that was mildly exacerbated by MPTP. However, PSI alone produced no sign of degeneration of the nigrostriatal dopaminergic pathway and did not exacerbate MPTP toxicity. To conclude, PSI administration does not provide a reliable phenotypic model of PD.

Rheumatoid arthritis is a chronic disease that results in a disabling and painful condition as it progresses to destruction of the articular cartilage and ankylosis of the joints. Although the cause of the disease is still unknown, evidence argues that autoimmunity plays an important part. There are increasing but contradictory views regarding serotonin being associated with activation of immunoinflammatory pathways and the onset of autoimmune reactions. We studied serotonin's involvement during collagen-induced arthritis in wild-type and Tph1(-/-) mice, which have markedly reduced peripheral serotonin levels. In wild-type mice, induction of arthritis triggered a robust increase in serotonin content in the paws combined with less inflammation. In Tph1(-/-) mice with arthritis, a marked increase in the clinical and pathologic arthritis scores was noticed. Specifically, in Tph1(-/-) mice with arthritis, a significant increase in osteoclast differentiation and bone resorption was observed with an increase in IL-17 levels in the paws and in Th17 lymphocytes in the draining lymph nodes, whereas T-regulatory cells were dampened. Ex vivo serotonin and agonists of the 5-HT2A and 5-HT2B receptors restored IL-17 secretion from splenocytes and Th17 cell differentiation in Tph1(-/-) mice. These findings indicate that serotonin plays a fundamental role in arthritis through the regulation of the Th17/T-regulatory cell balance and osteoclastogenesis.

This preliminary study shows, for the first time to our knowledge, decreased whole blood serotonin levels in AIDS patients as compared to healthy controls and cancer patients. The lowest serotonin levels were found in AIDS patients with neuropsychiatric symptoms. Finally the present data suggest an inverse relationship between serotonin level and AIDS severity.

Neuropathological studies have reported a strong neurofibrillary degeneration of the tuberomamillary nucleus, the region of origin of histamine neurons, in Alzheimer's disease (AD). Histaminergic neurons enhance cognition and memory, suggesting that their degeneration may contribute to the cognitive decline of AD. Besides neurons, the brain histaminergic system comprises mast cells and microglia that can also produce histamine. The level of activity of this histaminergic system in AD remained unknown. In the present study, we have measured the levels of the main histamine metabolite in brain, tele-methylhistamine (t-MeHA), an index of histaminergic system activity, in the cerebrospinal fluid (CSF) of 97 non-AD (controls) and 91 AD patients, males or females. t-MeHA levels in CSF of controls tended to be higher, although non-significantly, in females than in males. t-MeHA levels of controls and AD significantly increased with age (1.66 ± 0.13, 2.04 ± 0.12, and 2.76 ± 0.12 pmol/ml...

The loss of dopaminergic neurons in Parkinson's disease is associated with a glial reaction and the overproduction of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha). TNF-alpha acts via two different receptors, TNFR1 and TNFR2, and is believed to have both a neuroprotective and a deleterious role for neurons. In order to analyze the putative role of TNF-alpha in parkinsonism, we compared the effect of the parkinsonian drug 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice lacking TNFR1, TNFR2, or both receptors and in wild-type littermates. We show that MPTP does not affect spontaneous activity or anxiety in any of the groups and that it reduces motor activity on a rotarod in double knock out mice but not in mice lacking only one receptor. Postmortem analysis revealed no differences in the number of nigral dopaminergic neurons whatever the group. In contrast, striatal dopamine level was slightly decreased in double knock-out mice and more redu...

Spontaneous and all-trans-retinoic acid (RA)-induced differentiation of normal human monocytes and of leukemic THP-1 monocytes into macrophages resulted in a progressive loss of adenosine 3',5'-cyclic monophosphate production induced by histamine via typical H2 receptors (H2R). In THP-1 cells and in HL-60 human acute myelocytic leukemia cells, RA treatment increased the abundance of the 4.5-kb messenger RNA of the H2R gene fourfold, suggesting transcriptional control by a RA response element. Scatchard plots of [3H]tiotidine binding indicated the expression of H2R with similar affinity and binding capacity in THP-1 monocytes and macrophages, while the conversion of normal monocytes into macrophages decreased H2R density from 91.8 to 43.1 fmol/mg protein, with no change in affinity (Kd = 9.9 to 11.2 nM). In THP-1 macrophages, histamine inhibited 4 beta-phorbol 12-myristate 13-acetate (PMA)-induced H2O2 formation via the activation of H2 receptors. Expression of the H2R gene, histamine accumulation, and histidine decarboxylase activity were also demonstrated in normal human monocytes/macrophages and peripheral lymphocytes. Histamine and H2R may therefore affect, via intracrine, autocrine, and paracrine pathways, various immune and inflammatory responses of the lymphoid and myeloid progenitors and lineages in the bone marrow and peripheral tissues.

Autonomic and sensory nerves frequently contact mast cells contained in rabbit leptomeningeal arteries. We have previously shown that parasympathetic and peptidergic neurotransmitters can stimulate mast cell granule exocytosis and serotonin (5-HT) release. In the present study, we examined ex vivo the possible action of the main sympathetic neurotransmitter, norepinephrine (NE), on this exocytotic process. NE, which had no effect on mast cell 5-HT content per se, totally inhibited carbachol-induced 5-HT release and partially reduced neuropeptide-induced 5-HT release. Pretreatment with the alpha 1-adrenergic blocker did not affect the inhibitory effect of NE. Pretreatment with specific beta 1- or beta 2-adrenergic blockers antagonized this action, but the beta 2-blocker exerts a more specific dose-dependent antagonism. Together with our previous data, these results indicate that the equilibrium between autonomic and sensory nerves may determine the release of 5-HT from mast cells (pa...

Migraine is one of the few pathologies which gave rise to a tremendous number of physiopathological hypotheses. The variability of its clinical features and of the crisis initiating triggers, together with the numerous functional and/or biological abnormalities reported in migrainous patients, led to multiple 'theories' about migraine. For instance, migraine attacks may be associated with modifications of cerebral blood flow, and/or alterations at the cellular (neuronal and peripheral: platelets, mast cells, etc.) and subcellular (mainly mitochondrial) levels leading to variations of parameters such as serotonin, vasoactive neuropeptides, histamine, nitric oxide, neuroactive amino acids, etc. However, these modifications are mainly related to migraine attacks but not to migrainous patients. These emphasize how important is the distinction between the crisis mechanism(s) and the determinism of migraine illness. Despite the absence of any true animal model of migraine attack, the obtention, through the activation of the trigemino-vascular complex, of an experimental meningeal neurogenic inflammation was a clear breakthrough for the understanding of the migraine attack. Concerning the determinism of migraine, its familial characteristic has been known for a long time, but genetic studies started only recently. Despite some important contributions, the respective roles of genetic and environmental factors, as well as the transmission mode of migraine, remain largely to be determined. Practically, these genetic data, which really concern only a very peculiar form of migraine--the familial hemiplegic one--do not have presently any diagnostic or therapeutic application.

We examined the effect of kynurenic acid, a broad spectrum antagonist of excitatory amino acid receptors, on striatal extracellular glutamate and aspartate accumulation induced by a 30 min forebrain ischaemia in rats. Kynurenic acid, given systemically (500 mg kg-1, i.p.) or administered in situ through the dialysis probe (10 mM), markedly depressed the ischaemia-induced increase in glutamate and aspartate concentrations. These results indicate that, during forebrain ischaemia, local glutamate receptors play a major role in glutamate and aspartate accumulation in the striatum. Ischaemia-induced increase in extracellular concentrations of these excitatory amino acids may be due in part to a positive glutamatergic feedback loop via activation of NMDA and/or non-NMDA receptors.

Introduction La sérotonine (5-hydrohytryptamine, 5-HT) stimule la prolifération et la synthèse de collagène par les fibroblastes. Nous avons émis l’hypothèse que la sérotonine est impliquée dans la physiopathologie de la fibrose pulmonaire. Méthodes Des souris C57B1/6 ont reçu une dose unique de bléomycine par voie trans-trachéale à JO et ont ensuite été traitées par des injections quotidiennes intra-péritonéales d’un antagoniste du récepteur 5-HT2A (kétansérine, 2 mg/Kg), ou 5-HT2B (SB215505, 0,5 mg/Kg), ou d’un inhibiteur du transporteur de la 5-HT (fluoxétine (10 mg/Kg) de JO à J13. Les souris témoins ont reçu le solvant. Les souris ont été sacrifiées à J3, J7 et J14. Résultats Les traitements par kétansérine, SB215505 et fluoxétine améliorent la survie des souris par rapport aux contrôles, diminuent le contenu pulmonaire en collagène (de 30 %, 23 % et 16 % respectivement) et en ARNm du procollagène 1 (de 63 %, 60 % et 45 % respectivement) à J14. Le traitement par la kétansérine ...

Rabbit leptomeningeal arteries contain granular cells resembling mast cells that frequently contact autonomic and sensory nerve profiles. In the present in vitro study, we determined whether these cells could be stimulated by substance P (SP) and calcitonin gene-related peptide (CGRP), which are stored and released by sensory C fibers. Immunohistochemistry of the middle cerebral artery showed that 5-HT was stored only in mast cell-like granules. This pool of 5-HT decreased in a dose-dependent manner when exogenous SP and CGRP were added to the incubation solution or when endogenous neuropeptides were released from nerve terminals by capsaicin. The simultaneous administration of CGRP and SP induced a dramatic exocytosis and a 5-HT release significantly greater than the sum of the individual effects of the two neuropeptides. We conclude that, as in classical connective tissue mast cells, the amine content of these granular cells can be released by a degranulation process induced by ne...

A new procedure for serum inorganic sulphate determination is described. The method is simple, accurate and highly reproducible. It is based on radioisotopic dilution of 35S-sulphate by protein-free, phosphate-free serum. The decrease in initial 35S-sulphate specific activity (corresponding to added serum sulphate) is determined in the supernatant after partial precipitation of sulphate by barium ion. Serum sulphate is computed thereafter from a standard curve. Recovery of added sulphate from dialysed or undialysed serum was 100%. The intra- and interassay coefficients of variation were 3.5% and 4.1%, respectively. The serum sulphate concentration measured by this method in 93 normal subjects was 400 +/- 90 mumol/l (mean +/- SD), which agreed with the values reported in the literature. Serum sulphate did not correlate with sex (p greater than 0.40, n = 93), but a significant correlation with age was observed (r = 0.25, p less than 0.02, n = 93).

Thirty-five patients with fundic atrophic gastritis and achlorhydria were classified in two groups according to the presence or absence of fundic argyrophil, mostly enterochromaffinlike cell hyperplasia. Among the biologic and histologic parameters studied, the hyperplasic group differed only by a circulating hypergastrinemia and an antral G-cell hyperplasia. The histamine content, the histidine decarboxylase activity, and the mast cell number of fundic biopsies were determined in 10 controls, 16 of the preceding patients (11 with and 5 without fundic argyrophil-cell hyperplasia), and 5 patients with fundic atrophic gastritis and neither achlorhydria nor hyperplasia. Histamine content and histidine decarboxylase activity were increased only in the hyperplasic group despite an unchanged mast cell number. For all fundic biopsies the argyrophil-cell density was positively related to the histamine content. Finally, the argyrophil-cell hyperplasia occurring in fundic atrophic gastritis w...

Previously, we reported that rabbit cerebral arteries contain mast cells that frequently establish close contacts with parasympathetic-like nerve fibers. Here we have examined the possible function of this link by comparing the effects of carbachol and compound 48/80 on mast cell morphology and on the serotonin (5-HT) and histamine content of these arteries. In vivo, 2 micrograms/min of compound 48/80 or 1 micrograms/min of carbachol was infused for 30 min into one internal carotid artery of pentobarbital anesthetized rabbits, the contralateral artery being infused with vehicle. In vitro, the action of 10(-6) M carbachol was tested on isolated middle cerebral artery trees (MCAs) in the presence or absence of 10(-7) M atropine. The effects of carbachol were also tested in vitro on sympathectomized arteries. The 5-HT and histamine contents of all MCAs were measured by radioenzymatic assay, and fragments were prepared for electron microscopy. No histamine was detectable in any artery s...

A comparison was made in the blood levels of various cell types and biochemical substances and in lymphocyte antigens between 107 healthy sheep from a flock contaminated with scrapie (HC sheep) and 93 sheep from a noncontaminated flock (NC sheep), which served as a control population. Significant differences between the two groups of sheep were found in some of the levels, as had previously been found with lymphocyte antigens. The HC sheep, which included genetically resistant animals, could be distinguished from the NC sheep by their lower levels of various white cells, a noticeable decrease in urea, a moderate decrease in Mg2+ and Mn2+ ions, beta- and gamma-globulins, serotonin and vitamin B12, a strong increase in uric acid and a moderate increase in K+, Cl-, HCO3-, Zn2+, and Al3+ ions, as well as in total lipids and in the albumin to globulin ratio. In this HC population, the only enzyme with an increased level was aldolase; the levels of the other 7 enzymes measured were lowere...

In infantile autism, the serotoninergic (5-HT) hypothesis is corroborated by biological dosages and therapeutic effects of fenfluramine which decrease blood serotonin. However other drugs, such as dopaminergic agonists or antagonists, have therapeutic effects. Therefore, we tested the hypothesis that two dopaminergic (DA) drugs have a similar 5-HT effect underlying the therapeutic efficiency. We evaluated in a randomized, double-blind and cross-over study, the effects of a DA agonist (bromocriptine) and a DA antagonist (amisulpride) on platelet 5-HT in infantile autism. The prolactinemia, reflecting the DA action, has been also measured. Nine children, aged from 4 to 13 years, according to the DSM III for infantile autism, received either drug in a random order during four weeks with an in-between placebo period of six weeks. The dosages of platelet 5-HT and serum prolactin were carried out at the beginning and at the end of every phase of treatment (active or placebo) with radioenz...

Alterations in the serotonin (5-HT) system have been suggested as a mechanism of sleep apnea in humans and rodents. The objective is to evaluate the contribution of 5-HT to this disorder. We studied sleep and breathing (whole-body plethysmography) in mutant mice that lack monoamine oxidase A (MAOA) and have increased concentrations of monoamines, including 5-HT. Compared to wild-type mice, the mutants showed similar amounts of slow wave sleep (SWS) and rapid eye movement sleep (REMS), but exhibited a 3-fold increase in SWS and REMS apnea indices. Acute administration of the MAOA inhibitor clorgyline decreased REMS amounts and increased the apnea index in wild-type but not mutant mice. Parachlorophenylalanine, a 5-HT synthesis inhibitor, reduced whole brain concentrations of 5-HT in both strains, and induced a decrease in apnea index in mutant but not wild-type mice. Our results show that MAOA deficiency is associated with increased sleep apnea in mice and suggest that an acute or ch...

To observe the morphology and physiology of the retina in rats 11 weeks after a constant (24-hour) but moderate (500-lux) illumination for 1 week. Levels of aspartate, gamma-aminobutyric acid (GABA), glutamate, glutamine, and taurine were measured by high-pressure liquid chromatography (HPLC) in the retina and vitreous humor of albino (Wistar) and pigmented (Long-Evans) rats. Semithin sections were used to determine retinal morphology. The TUNEL method was used to detect cells degenerating by apoptosis. Because the GABAergic system has been shown to be particularly sensitive to the loss of photoreceptors, an additional immunohistochemical study using anti-GABA, anti-glutamate decarboxylase (GAD)(67) and anti-GAD(65) antibodies was performed. No apparent morphologic changes were found in the retina of pigmented rats after constant illumination, whereas in albino rats disappearance of photoreceptors (except in the extreme retinal periphery) and cell bodies was observed. A significant ...