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M Tafti

Publications and source records attributed to M Tafti.

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

Localization of candidate genomic regions influencing paradoxical sleep in mice.

Quantitative trait loci (QTL) approach was used in CXB recombinant inbred mice for preliminary identification of candidate regions on the mouse genome that influence sleep. The only provisional QTLs identified were associated with paradoxical sleep (PS). PS during the light period was associated with markers on chromosome 7 between 7 and 20 centimorgan from the centromere. For PS during the dark period, a single QTL was identified on chromosome 5, near the Clock gene. The 24 h amount of PS was influenced by markers on chromosomes 2, 17, and 19. This first QTL mapping study strongly suggests that a complex behaviour like PS can be controlled by only a few genes.

Animals↗
PubMed1997

Mesopontine organization of cholinergic and catecholaminergic cell groups in the normal and narcoleptic dog.

Canine narcolepsy is a unique experimental model of a human sleep disorder characterized by excessive daytime sleepiness and cataplexy. There is a consensus recognition of an imbalance between cholinergic and catecholaminergic systems in narcolepsy although the underlying mechanisms remain poorly understood. Possible substrates could be an abnormal organization, numbers and/or ratio of cholinergic to catecholaminergic cells in the brain of narcoleptic dogs. Therefore, we sought to characterize the corresponding neuronal populations in normal and narcoleptic dogs (Doberman Pinscher) by using choline acetyltransferase (ChAT), nicotinamide adenosine dinucleotide phosphate (NADPH)-diaphorase, tyrosine hydroxylase (TH), and dopamine beta-hydroxylase (DBH). Cholinergic cell groups were found in an area extending from the central to the gigantocellular tegmental field and the periventricular gray corresponding to the pedunculopontine tegmental nucleus (PPT), the laterodorsal tegmental nucleus (LDT), and the parabrachial nucleus. An almost perfect co-localization of ChAT and NADPH-diaphorase was also observed. Catecholaminergic cell groups detected included the ventral tegmental area, the substantia nigra, and the locus coeruleus nucleus (LC). The anatomical distribution of catecholaminergic neurons was unusual in the dog in two important aspects: i) TH- and/or DBH-immunoreactive neurons of the LC were found almost exclusively in the reticular formation and not within the periventricular gray, ii) very few, if any TH-positive neurons were found in the central gray and dorsal raphe. Quantitative analysis did not reveal any significant differences in the organization and the number of cells identified in the LDT, PPT, and LC of normal and narcoleptic dogs. Moreover, the cholinergic to catecholaminergic ratio was found identical in the two groups. In conclusion, the present results do not support the hypothesis that the neurochemical imbalance in narcolepsy could result from abnormal organization, numbers, or ratio of the corresponding neuronal populations.

Animals↗
PubMed1997

Circadian distribution of rest/activity in narcoleptic and control dogs: assessment with ambulatory activity monitoring.

Like human narcoleptics, narcoleptic dogs display cataplexy, fragmented sleep and excessive daytime sleepiness. Cataplexy in dogs can easily be quantified using a simple behavioural bioassay, the Food Elicited Cataplexy Test. In contrast, daytime sleepiness and fragmented sleep are more difficult to measure, as long-term, labour-intensive polygraphic recordings in surgically-implanted animals are needed. In the current study, 24-h rest/activity patterns in genetically narcoleptic, asymptomatic heterozygous and control Dobermans were compared using small sized ambulatory activity monitoring devices under 12-h light/dark conditions. Control and heterozygous dogs were found to be more active during the light period than during the dark period, thus demonstrating a clear 24-h rest/activity cycle. In contrast, narcoleptic dogs were relatively inactive during the light period and did not show a clear rest/activity pattern, a result similar to that of human narcoleptics. Considering the fact that narcoleptic dogs show shorter sleep latency and sleep significantly more during the daytime than control dogs, the decrease in activity in narcoleptic dogs during the daytime is most likely a reflection of increased daytime napping in these animals. Ambulatory activity monitoring may be a useful non-invasive method for future pharmacological and development studies in the narcoleptic canine model.

Animals↗
PubMed1996

Local administration of dopaminergic drugs into the ventral tegmental area modulates cataplexy in the narcoleptic canine.

Cataplexy in the narcoleptic canine may be modulated by systemic administration of monoaminergic compounds. In the present study, we have investigated the effects of monoaminergic drugs on cataplexy in narcoleptic canines when perfused locally via microdialysis probes in the amygdala, globus pallidus/putamen, basal forebrain, pontine reticular formation and ventral tegmental area of narcoleptic and control Doberman pinchers. Cataplexy was quantified using the Food-Elicited Cataplexy Test and analyzed by electroencephalogram, electroculogram and electromyogram. Local perfusion with the monoaminergic agonist quinpirole, 7-OH-DPAT and BHT-920, into the ventral tegmental area produced a dose-dependent increase in cataplexy without significantly reducing basal muscle tone. Perfusion with the antagonist raclopride in the same structure produced a moderate reduction in cataplexy. Local perfusion with quinpirole, 7-OH-DPAT and BHT-920 into the globus pallidus/putamen also produced an increase, while raclopride produced a decrease, in cataplexy in narcoleptic canines. In control animals, none of the above drugs produced cataplexy or muscle atonia when perfused into either the ventral tegmental area or the globus pallidus/putamen. Other monoaminergic drugs tested in these two brain areas; prazosin, yohimbine, amphetamine, SKF 38393 and SCH 23390 had no effects on cataplexy. Local perfusion with each of the above listed drugs had no effect on cataplexy in any of the other brain regions examined. These findings show that cataplexy may be regulated by D2/D3 dopaminergic receptors in the ventral tegmental area and perhaps the globus pallidus/ putamen. It is suggested that neurons in the mesolimbic dopamine system of narcoleptics are hypersensitive to dopaminergic autoreceptor agonists.

Amygdala↗
PubMed1996

Thalidomide, a hypnotic with immune modulating properties, increases cataplexy in canine narcolepsy.

Thalidomide is a sedative hypnotic that was widely used in the 1950s but was withdrawn due to its teratogenic properties. The compound has recently been reintroduced as an immune modulating agent. Thalidomide significantly aggravates canine cataplexy, a pathological manifestation of rapid eye movement (RFM) sleep atonia seen in narcolepsy. This compound also increases REM sleep and slow wave sleep in these animals. In vitro receptor binding and enzyme assays demonstrate that thalidomide does not bind to or enzymatically modulate the neurotransmitter systems reported to be involved in the regulation of cataplexy. Thalidomide may therefore affect cataplexy through its immune modulation properties. Further studies on the mechanisms of action of thalidomide should increase our understanding of the pathophysiology of this disabling disorder.

Animals↗
PubMed1996

Major histocompatibility class II molecules in the CNS: increased microglial expression at the onset of narcolepsy in canine model.

Human narcolepsy is a neurological disorder known to be closely associated with HLA-DR2 and DQB1*0602. Because most autoimmune diseases are HLA-associated, a similar mechanism has been proposed for narcolepsy. However, neither systemic nor CNS evidence of an autoimmune abnormality has ever been reported. In this study, major histocompatibility (MHC) class I and class II expression was studied in the CNS of human and canine narcoleptics using immunohistochemistry and Northern analysis. Results indicated that canine narcolepsy is associated with a significant increase of MHC class II expression by the microglia. Moreover, the highest values were found between 3 and 8 months of age, strikingly concomitant to the development of narcolepsy in the canine model. In humans, class II expression was not found significantly different between control and narcoleptic subjects. This result could be explained by the old age of the subjects (69.86 +/- 5.31 and 68.36 +/- 4.74 years in narcoleptics and controls, respectively), because class II expression is significantly correlated with age in both humans and dogs. For the first time, this study demonstrated that the expression of MHC class II molecules in the CNS is age-dependent and that a consistent increase of their expression by the microglia might be critically involved in the development of narcolepsy.

Aged↗
PubMed1995

Narcolepsy and immunity.

Narcolepsy is a neurological disorder known to be associated with human leukocyte antigen (HLA)-DQB1*0602 in humans. In a canine model, the disorder is also genetically linked to a gene of high homology with the human mu-switch-like immunoglobulin (Ig) gene (current LOD score 13.6 at 0% recombination). Since association with HLA or other immune function polymorphic genes (T cell receptor of Ig, mainly) is a hallmark of most autoimmune diseases, it is proposed that autoimmunity may also play a role in the development of narcolepsy. Arguments for and against this hypothesis are reviewed. It is shown that both on the basis of the most recent molecular studies, and because of some of its clinical features, narcolepsy may be an autoimmune disorder. However, neither systemic nor central nervous system (CNS) evidence of any autoimmune abnormality have ever been found. To reconcile this discrepancy, it is suggested that the pathological immune process involved in narcolepsy could be difficult to detect because it is restricted to a very small region of the brain or targets a low abundance neuroeffector. Alternatively, it is possible that a more fundamental relationship is involved between sleep generation and immune regulation. The pathophysiology of narcolepsy may then involve new CNS-immune mechanisms that may shed new light on the sleep process itself.

Adolescent↗
PubMed1995

Muscle atonia is triggered by cholinergic stimulation of the basal forebrain: implication for the pathophysiology of canine narcolepsy.

Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness and rapid eye movement (REM) sleep-related symptoms, such as cataplexy. The exact pathophysiology underlying the disease is unknown but may involve central cholinergic systems. It is known that the brainstem cholinergic system is activated during REM sleep. Furthermore, REM sleep and REM sleep atonia similar to cataplexy can be triggered in normal and narcoleptic dogs by stimulating cholinergic receptors within the pontine brainstem. The pontine cholinergic system is, therefore, likely to play a role in triggering cataplexy and other REM-related abnormalities seen in narcolepsy. The other cholinergic system that could be involved in the pathophysiology of narcolepsy is located in the basal forebrain (BF). This system sends projections to the entire cerebral cortex. Since acetylcholine release in the cortex is increased both during REM and wake, the basocortical cholinergic system is believed to be involved in cortical desynchrony. In the current study, we analyzed the effect of cholinergic compounds injected into the forebrain structures of narcoleptic and control dogs. We found that carbachol (a cholinergic agonist) injected into the BF triggers cataplexy in narcoleptic dogs while it increases wakefulness in control dogs. Much higher doses of carbachol bilaterally injected in the BF were, however, shown to trigger muscle atonia even in control dogs. These results suggest that a cholinoceptive site in the BF is critically implicated in triggering muscle atonia and cataplexy. Together with similar results previously obtained in the pontine brainstem, it appears that a widespread hypersensitivity to cholinergic stimulation may be central to the pathophysiology of canine narcolepsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Effects of zolpidem on the architecture and cyclical structure of sleep in poor sleepers.

Effects of zolpidem, a short acting non benzodiazepine hypnotic, have been studied in eight female poor sleepers, aged 25 to 54 years, documented during two consecutive adaptation nights. Subjects were recorded according to a 22 day single blind study. Placebo was given orally at bedtime on nights 2-4, zolpidem on nights 5-20 and finally placebo on nights 21-22. Polygraphic recordings (conventional analysis) were performed on nights 1-6; 12, 13; 19-22. Parameters of sleep continuity, sleep architecture and cyclical structure of sleep were studied. Zolpidem 10 mg showed a hypnotic effect on poor sleepers. It reduced sleep latency, increased total sleep time and decreased the number of awakenings during all recorded nights. During the first post-drug night a rebound insomnia was observed in two subjects only. Zolpidem did not increase specifically stage 2 to the detriment of stages 3 and 4 but it restored them during the first nights of administration. Study of the rapid eye movements-non rapid eye movements (REM-NREM) sleep cycles structure showed that the increase of stages 3 and 4 occurred only during the first part of the night. Finally, zolpidem had no effect on REM sleep temporal distribution.

Adult↗
PubMed1994

Objective and subjective sleep disturbances in patients with rheumatoid arthritis. A reappraisal.

OBJECTIVE: To assess objective and subjective evidence of sleep disturbances in patients with rheumatoid arthritis (RA) and to examine correlations between parameters of inflammatory activity and sleep pathology. METHODS: Nineteen RA patients and 19 age-matched healthy control subjects underwent all-night polysomnography on 2 consecutive nights. RA patients were also evaluated for daytime sleepiness by mean sleep latency test and responded to a self-report questionnaire on their first night. RESULTS: Whereas normal sleep architecture is conserved in RA, we confirmed former findings of severe sleep fragmentation and an enhanced presence of primary sleep disorders. No correlation exists between RA activity and the sleep disorders. Subjective assessment was not consistent with the objective evidence of sleep disruption, unlike the findings in patients with fibrositis. CONCLUSION: Sleep is severely disturbed in patients with RA, regardless of the inflammatory disease activity. The specificity of the sleep disorders assessed needs confirmation, as does specific sleep therapy for these patients.

Adult↗
PubMed1994

Cholinergic mechanisms in canine narcolepsy--I. Modulation of cataplexy via local drug administration into the pontine reticular formation.

Cataplexy in the narcoleptic canine has been shown to increase after systemic administration of cholinergic agonists. Furthermore, the number of cholinergic receptors in the pontine reticular formation of narcoleptic canines is significantly elevated. In the present study we have investigated the effects of cholinergic drugs administered directly into the pontine reticular formation on cataplexy, as defined by brief episodes of hypotonia induced by emotions, in narcoleptic canines. Carbachol and atropine were perfused through microdialysis probes implanted bilaterally in the pontine reticular formation of freely moving, narcoleptic and control Doberman pinschers. Cataplexy was quantified using the Food-Elicited Cataplexy Test, and analysed using recordings of electroencephalogram, electrooculogram and electromyogram. Cataplexy was characterized by a desynchronized electroencephalogram and a drop in electromyogram and electrooculogram activity. In narcoleptic canines, both unilateral and bilateral carbachol (10(-5) to 10(-3) M) produced a dose-dependent increase in cataplexy, which resulted in complete muscle tone suppression at the highest concentration. In control canines, neither bilateral nor unilateral carbachol (10(-5) to 10(-3) M) produced cataplexy, although bilateral carbachol, did produce muscle atonia at the highest dose (10(-3)). The increase in cataplexy after bilateral carbachol (10(-4) M) was rapidly reversed when the perfusion medium was switched to one containing atropine (10(-4) M). Bilateral atropine (10(-3) to 10(-2) M) alone did not produce any significant effects on cataplexy in narcoleptic canines; however, bilateral atropine (10(-2) M) did reduce the increase in cataplexy produced by systemic administration of physostigmine (0.05 mg/kg, i.v.). These findings demonstrate that cataplexy in narcoleptic canines can be stimulated by applying cholinergic agonists directly into the pontine reticular formation. The ability of atropine to inhibit locally and systemically stimulated cataplexy indicates that the pontine reticular formation is a critical component in cholinergic stimulation of cataplexy. Therefore, it is suggested that the pontine reticular formation plays a significant role in the cholinergic regulation of narcolepsy.

Analysis of Variance↗
PubMed1994

Life events in the year preceding the onset of narcolepsy.

A multifactorial etiology for narcolepsy has been postulated, stressing the importance of environmental factors in the clinical onset of the condition. Our study evaluated the occurrence of stressful life events in the year preceding the onset of narcolepsy. Fifty narcoleptic and 50 control subjects completed a life event questionnaire (the Schedule of Recent Experiences). The proportion of narcoleptic subjects reporting the presence of life events in the year preceding the onset of narcolepsy was significantly greater than the proportion of control subjects reporting life events in the corresponding year. Moreover the weight of life events was increased in narcoleptic subjects in comparison with controls. In conclusion life events seem to be increased in narcoleptic subjects in the year preceding the onset of their condition. However a number of other factors could not be taken into consideration, which limits the full significance of these data.

Adolescent↗
PubMed1994

Homeostasis and narcolepsy.

Narcolepsy is characterized by irresistible daytime sleep episodes and cataplectic attacks. Because of the finding of an ultradian rhythmicity of slow-wave sleep in narcolepsy, an alteration of nonrapid eye movement sleep homeostatic regulation has been hypothesized to explain the impairment of the sleep-wakefulness cycle. This hypothesis was tested by two different methods: 1) a sleep-deprivation method (16 or 24 hours) increasing the prior sleep wakefulness and 2) a bed-rest method shortening the prior sleep wakefulness. In both studies normal subjects, sex- and age-matched to narcoleptic subjects, served as controls. Although some differences could be evidenced between the two groups, it was clearly shown that the homeostatic process was functional in narcolepsy and that narcoleptics seemed to be more sensitive to homeostatic regulation of sleep than normal subjects.

Adolescent↗
PubMed1994

Cholinergic regulation of cataplexy in canine narcolepsy in the pontine reticular formation is mediated by M2 muscarinic receptors.

Both rapid eye movement sleep and cataplexy in the narcoleptic canine have been shown to increase after both systemic and local administration of cholinergic agonists in the pontine reticular formation. Furthermore, binding studies indicate an increase in the number of M2 muscarinic receptors in the pontine reticular formation of narcoleptic canines. In the present study we have investigated the receptor subtypes involved in mediating the cholinergic stimulation of cataplexy, as defined by brief periods of hypotonia induced by emotions, within the pontine reticular formation of narcoleptic canines. Specific cholinergic and monoaminergic agonists and antagonists, and excitatory or inhibitory amino-acid neurotransmitter receptor agonists, were perfused through microdialysis probes implanted bilaterally in the pontine reticular formation of narcoleptic canines, and cataplexy was monitored using the Food-Elicited Cataplexy Test and recordings of electroencephalogram, electrooculogram and electromyogram. In narcoleptic canines, bilateral perfusion with oxotremorine (M2 muscarinic) (10(-5)-10(-3) M) in the pontine reticular formation produced a dose-dependent increase in cataplexy, which reached complete muscle atonia (status cataplecticus) during the highest concentration. In control canines bilateral perfusion with oxotremorine (10(-5)-10(-3) M) did not produce any cataplectic attacks, but did produce muscle atonia after the highest concentration. Bilateral perfusion with either McN-A-343 (M1 muscarinic) or nicotine (both 10(-5)-10(-3) M) did not have any effect on cataplexy in either narcoleptic or control canines. The increase in cataplexy in narcoleptic canines produced by local perfusion with carbachol (10(-4) M) followed by equimolar perfusion with a muscarinic antagonist was rapidly reversed by atropine (muscarinic) and gallamine (M2 muscarinic), partially reversed by 4-DAMP (M3/M1 muscarinic) and completely unaffected by pirenzepine (M1 muscarinic). Bilateral perfusion with excitatory, glutamatergic receptor agonists N-methyl-D-aspartate, AMPA (both at 10(-4)-10(-3) M) and kainic acid (10(-5)-10(-4) M) did not have any effect on cataplexy, whereas bilateral perfusion with the inhibitory GABAergic receptor agonist muscimol (10(-4)-10(-3) M) produced a moderate increase in cataplexy in the narcoleptic canines. Bilateral perfusion with numerous monoaminergic compounds, BHT-920 (alpha-2 agonist), yohimbine (alpha-2 antagonist), propranolol (beta antagonist) and prazosin (alpha-1 antagonist), did not have any effect on cataplexy. These findings demonstrate that cholinergic regulation of cataplexy in the narcoleptic canine at the level of the pontine reticular formation is mediated by M2, and possibly M3, muscarinic receptors. The effects of muscimol indicate that the stimulation of cataplexy might be elicited by local neuronal inhibition.

Animals↗
PubMed1993

Developmental regulation of carbonic anhydrase expression in mouse dorsal root ganglia.

The development of proprioceptive neurons in mammalian dorsal root ganglia (DRG) remains poorly documented since few specific markers for these neurons are known. Recent studies suggest that carbonic anhydrase (CA) is a specific marker of this functionally defined neuronal population. The present study was designed to investigate the development of CA staining in sensory neurons. We investigated CA reactivity in mouse lumbar DRGs from embryonic day 13 (E13) to postnatal day 100 (P100) using a modified cytoenzymatic Hansson method. Neuronal CA reactivity was first detected during the perinatal stage (1-3% of DRG neurons) and increased progressively from P0 to P60 when it reached a plateau (about 30-33% of DRG neurons). Statistical morphometric analysis was used to define whether CA staining identifies the same population(s) during development. The results demonstrated that, whatever the stage of development, reactive neuronal cells are included in the well-defined large type A population. The possibility that neuronal CA expression is a reliable marker of the 'functional activity' of the proprioceptive neurons in mammals is discussed. The late development expression of the enzyme (after target innervation) raises the possibility of a regulation of the CA phenotype by neuron-target interactions.

Animals↗
PubMed1993

[The effects of modafinil (300mg) on sleep, sleepiness and arousal in narcoleptic patients].

CNS stimulants are the most widely used drugs to treat narcolepsy which is characterized by the excessive daytime sleepiness and typically associated with cataplexy. However, a number of side effects may often arise with this therapeutic approach. Thus, investigating new drugs which are efficient but well tolerated is of utmost importance in the treatment of narcolepsy. Although modafinil, an alpha-1 adreno-receptor agonist, has been reported to bring substantial awakening properties in animals, the studies performed in man, particularly in narcoleptic subjects, are few. In the present study, we evaluated the effects of a 300 mg daily dose of modafinil on sleepiness and psychomotor performance of 16 narcoleptic subjects. The major effect of modafinil in narcoleptic subjects was a decrease of daytime sleepiness and corresponding improvement of performances involving attentive functions. However, the learning effect in psychomotor tests may mask the drug effect.

Adolescent↗
PubMed1993

Pharyngeal CT studies in patients with mild or severe upper airway obstruction during sleep.

The upper airway cross-sectional areas were studied with pharyngeal computed tomography (CT) at the nasopharyngeal, velopharyngeal, tongue base and hyoid bone levels in 119 consecutively investigated patients with a snoring complaint. According to their findings in an all-night static charge sensitive bed (SCSB) recording, the subjects were divided into four equally sized groups with increasing severity of nocturnal breathing disturbance. The body mass index (BMI) increased and the minimal cross-sectional area at the velopharyngeal level decreased consistently as a function of the severity of nocturnal breathing disturbance. The minimal cross-sectional area at the hyoid bone level showed a biphasic trend, with an initial decrease but a final increase, as the degree of nocturnal breathing disturbance aggravated. The results contradict the idea of gradually increasing anatomical narrowing of the upper airways in general as the nocturnal breathing disturbance exacerbates and support the concept of two anatomically determined entities of partial and complete upper airway obstruction during sleep.

Airway Obstruction↗