prostaglandin-d2 and Sleep-Wake-Disorders

Recent advancements in molecular engineering techniques have enabled us to study sleep of animals lacking or overproducing any protein molecule we are interested in. Abnormalities in sleep have already been observe in knockout mice lacking the gene for prion protein, 55 kD-receptor of tumor necrosis factor, etc. We also started a project to examine the effect of the loss or the overproduction of prostaglandin D synthase in sleep. The enzyme is responsible for biosynthesis of prostaglandin D2, the most potent endogenous substance to promote sleep reported so far. We generated both knockout and transgenic mice of prostaglandin D synthase. We are currently analysing the sleep of these mutant mice.

Topics: Animals; Antigens, CD; Humans; Intramolecular Oxidoreductases; Lipocalins; Mice; Mice, Knockout; Mice, Transgenic; Mutation; Prions; Prostaglandin D2; Receptors, Tumor Necrosis Factor; Receptors, Tumor Necrosis Factor, Type I; Sleep Wake Disorders

Prostaglandin D2 (PGD2) induces sleep and may play a role in sleep and neurological disorders. We investigated PGD synthase (PGDS) levels in various sleep and neurological disorders.. Sixty-three patients with neurological or sleep disorders (Parkinson's disease with excessive daytime sleepiness (PDS), n = 19; PD without sleepiness (PDWS), n = 14; Alzheimer's disease (AD), n = 10; narcolepsy (NA), n = 10; sleep apnea syndrome (SAS), n = 10) and 21 healthy controls were included in this study. Plasma lipocalin-type PGDS (L-PGDS) and glutathione-dependent hematopoietic PGDS (H-PGDS) levels were assessed using an enzyme-linked immunosorbent assay.. H-PGDS levels were not significantly different among the groups. Compared with healthy controls, the PDWS, PDS and AD groups had higher levels of L-PGDS. Neither H-PGDS nor L-PGDS levels correlated with scores on the Epworth Sleepiness Scale or Pittsburgh Sleep Quality Index in any group.. We found higher levels of L-PGDS in patients with neurodegenerative diseases such as PD and AD. Whether increased L-PGDS levels reflect underlying sleepiness or the pathophysiology of neurodegenerative diseases needs further study.

Topics: Humans; Intramolecular Oxidoreductases; Lipocalins; Nervous System Diseases; Prostaglandin D2; Sleep; Sleep Wake Disorders

Since it is recognized that cyclo-oxygenase-2 mediates nociception and the sleep-wake cycle as well, and that acute inflammation of the temporomandibular joint (TMJ) results in sleep disturbances, we hypothesized that cyclo-oxygenase-2 inhibitor would restore the sleep pattern in this inflammatory rat model. First, sleep was monitored after the injection of Freund's adjuvant (FA group) or saline (SHAM group) into the rats' temporomandibular joint. Second, etoricoxib was co-administered in these groups. The Freund's adjuvant group showed a reduction in sleep efficiency, in rapid eye movement (REM), and in non-REM sleep, and an increase in sleep and REM sleep latency when compared with the SHAM group, while etoricoxib substantially increased sleep quality in the Freund's adjuvant group. These parameters returned progressively to those found in the SHAM group. Etoricoxib improved the sleep parameters, suggesting the involvement of the cyclo-oxygenase-2 enzyme in acute inflammation of the TMJ, specifically in REM sleep.

Topics: Acute Disease; Animals; Arthritis, Experimental; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Etoricoxib; Male; Prostaglandin D2; Pyridines; Random Allocation; Rats; Rats, Wistar; Sleep Wake Disorders; Sleep, REM; Sulfones; Temporomandibular Joint Disorders

Sleep abnormalities have been consistently observed in patients with schizophrenia. Elevated levels of corticotropin releasing factor (CRF) and prostaglandins (PGs) in the cerebrospinal fluid (CSF) of patients with schizophrenia have been reported, and these neurochemical substances, known to modulate sleep in experimental animals, may play a role in these sleep abnormalities. In this study, we measured PGD2, PGE2, PGF2alpha and CRF levels in the CSF of 14 unmedicated schizophrenic patients and 14 age- and sex-matched control subjects. Polysomnographic recordings were also carried out for each subject. As expected, the sleep of the schizophrenic subjects significantly differed from that of the controls; schizophrenic subjects had a longer sleep onset latency, slept less, spent fewer minutes in stage 2 sleep and had a lower sleep efficiency. We could not, however, detect any differences in CSF CRF and PG levels between normal and schizophrenic subjects, nor could we find any correlation between CSF variables and sleep parameters in the schizophrenic subjects and the non-psychiatric controls. These results do not favor the hypothesis of a role for CRF or PGs in the pathophysiology of sleep disturbances in schizophrenia.

Topics: Adult; Corticotropin-Releasing Hormone; Dinoprost; Dinoprostone; Humans; Male; Prostaglandin D2; Prostaglandins; Schizophrenia; Sleep; Sleep Wake Disorders