Awaking effect of prostaglandin E2 in freely moving rats

Self Cite

108

To examine the function of prostaglandin (PG) D synthase (PGDS) gene, as well as endogenously produced PGD 2 in sleep regulation in vivo, we generated transgenic (TG) mice that overexpress human PGDS gene to study their sleep behavior. Although no difference was observed in the sleep͞wake patterns between wild-type and TG mice, a striking time-dependent increase in non-rapid eye movement (NREM), but not in rapid eye movement (REM), sleep was observed in two independent lines of TG mice after stimulation by tail clipping. Concomitantly, the spontaneous locomotor activity of TG animals was drastically decreased in response to the tail clip. Induction of NREM sleep in TG mice was positively correlated with the PGD2 production in the brain. Sleep, locomotion, and PGD2 content were essentially unchanged in wild-type mice after tail clipping. The results with TG mice demonstrate the involvement of the PGDS gene in the regulation of NREM sleep.

Section: Resultsmentioning

confidence: 99%

Prostaglandin D synthase gene is involved in the regulation of non-rapid eye movement sleep

Pinzar¹,

Kanaoka²,

Inui³

et al. 2000

Self Cite

108

“…When injected intaventricularly or in the periventricular region, a number of molecules have been shown to exert powerful influences on these functions. These molecules include prostaglandins D2 and E2 (18,19) and deltasleep-inducing peptide (20), regulating sleep-wakefulness, and endogenous opioid peptides, modulating pain-related neural activity (17). It is tempting to speculate that these molecules have functional roles requiring signal transmission through the putative communication channel between the cerebrospinal fluid and midline groups of neurons.…”

Section: Discussionmentioning

confidence: 99%

Monoclonal antibody R2D5 reveals midsagittal radial glial system in postnatally developing and adult brainstem.

Mori¹,

Ikeda²,

Hayaishi³

1990

Radial glial cells and their processes play critical roles in organizing the spatial arrangement of the nervous system in the embryonic brain. It has been thought that following completion of their roles in the embryo, most of the radial glial processes disappear before or shortly after birth. Here we use R2D5, a monoclonal antibody to a soluble cytosolic protein, to demonstrate that a specific system of midsagittal radial glial cells persists in postnatal and adult brain. In the brainstem of postnatally developing and adult rabbits and cats, the R2D5-positive processes of radial glial cells were observed to be arranged in a precisely parallel array at the midsagittal seam. These radial glial processes formed a continuous palisade separating the right and left brainstem. In early postnatal animals, R2D5-positive radial processes were found to reach the pial surface and to cover the entire midsagittal seam of the brainstem. These processes embraced dendrites and somata of neurons in almost all of the midsagittal nuclei, including the raphe nuclei, suggesting that the radial glial cells may interact with the midsagittal groups of neurons. In addition, the palisade of R2D5-positive radial processes formed loose openings for crossing axonal bundles at the midline decussations of fiber tracts. In more mature brains, somata of R2D5-positive radial glial cells that had migrated ventrally were observed within the palisades, and in adult cats, most of the R2D5-positive radial processes were found to have retracted from the ventral parts of the midsagittal seam. The spatial arrangement of R2D5-positive processes suggests that they may have persistent functional roles as an interface between ventricular humoral signals and midsagittal groups of neurons in the postnatally developing brainstem and in the adult brainstem. The structure of the midline glial system suggests also that it plays a role in organizing the spatial arrangement of decussating axons during development.Radial glial cells are process-bearing ependymal cells lining the surface of brain ventricles and the central canal of the spinal cord. These are the first class of glial cells to appear during embryonic development and they are thought to play critical roles in organizing the spatial arrangement of the nervous system (1, 2). In lower vertebrates, for example, radial processes of ependymal cells have been reported to form channels for growing axons during both regeneration and embryonic development and thus have been suggested to display on their surfaces trace pathways that the axons follow toward their destination (3, 4). In the mammalian embryo, ependymal cells project their processes (radial glial fibers) to almost all regions of the brain and are thought to supply pathways guiding the migration of newly generated neurons (1, 5). Most of these mammalian radial glial cells disappear before birth (5) and process-bearing ependymal cells (tanycytes) have been reported to be present only in restricted portions of the adult brain (6).Using an antibod...

“…The pH of the solutions was adjusted to 7.2 by bubbling a mixture of 95% C02/5% 02 or by addition of 0.2 M NaOH. SWS, PS, and wakefulness were scored on EEG and EMG recordings by visual determination, as described (6). The minimal scoring interval for each vigilance state was set at 15 sec.…”

Section: Methodsmentioning

confidence: 99%

“…Prostaglandins (PGs) D2 and E2, which are the major PGs in the brain of mammals, have been postulated to be endogenous factors for regulating sleep-wake activities in the rat and monkey (1, 2)-the former promoting sleep (3,4) and the latter augmenting wakefulness (5)(6)(7). Naito et al (8) reported the effects of intracerebroventricularly and systemically administered cyclooxygenase inhibitors such as indomethacin and diclofenac sodium on the sleep-wake activities of rats.…”

mentioning

confidence: 99%

Inhibition of sleep in rats by inorganic selenium compounds, inhibitors of prostaglandin D synthase.

Matsumura

Takahata

Hayaishi

1991

Prostaglandin (PG) D2 has been postulated to be an endogenous sleep-promoting factor in rats, and SeC14 and Na2SeO3 recently have been shown to inhibit the PGD synthase (prostaglandin-H2 D-isomerase, EC 5.3.99.2) activity of rat brain. The effect of these selenium compounds on sleep-wake activities was examined in freely moving rats along with their effects on brain temperature, food and water intake, and behavior. Test substances were administered for 6 hr into the third ventricle of rats, using a microdialysis technique. SeC4, time-and dose-dependently, inhibited sleep at perfusion rates of 60 pmol/0.2 jcl per min and higher, and the inhibition was almost complete at rates >200 pmol/0.2 gIl per min. The effect was reversible and was followed by a rebound. Na2SeO3 exhibited similar effects, but Na2SO3 did not show any effect on sleep. Simultaneous administration of dithiothreitol eliminated the sleep-inhibiting effects of these selenium compounds. These findings indicate that the decrease in sleep is due to inhibition of the PGD synthase activity in the brain by SeCL4 as-well as Na2SeO3. During the inhibition of sleep, the rats in general showed an activation of behavior with moderate elevation of brain temperature and a detectable increase in food and water intake, suggesting that the sleep-inhibited state of the rats was similar to the physiological state of wakefulness and that the inhibitory effect was not due to the general toxicity of selenium.Prostaglandins (PGs) D2 and E2, which are the major PGs in the brain of mammals, have been postulated to be endogenous factors for regulating sleep-wake activities in the rat and monkey (1, 2)-the former promoting sleep (3, 4) and the latter augmenting wakefulness (5-7). Naito et al. (8) reported the effects of intracerebroventricularly and systemically administered cyclooxygenase inhibitors such as indomethacin and diclofenac sodium on the sleep-wake activities of rats. However, these inhibitors are not specific for PG0)2 but prevent the synthesis of PGH2 from arachidonate, which in turn affects the consequent production of various eicosanoids, including PGD2 and E2. The rat brain PGD synthase (prostaglandin-H2 D-isomerase, EC 5.3.99.2) was purified to homogeneity and characterized by Urade et al. (9,10). More recently, Islam et al. (11) demonstrated in an in vitro study that inorganic quadrivalent selenocompounds, such as SeCL4 and Na2SeO3, inhibited the activity of the rat brain PGD synthase whereas other enzymes in the arachidonate cascade were not affected. Therefore, these selenocompounds may serve as useful probes for elucidating the role of endogenous PGD2 in the physiological sleep-wake regulation.In the present study, the effects of selenocompounds on sleep-wake activities, brain temperature, food and water intake, and behavior were examined in freely moving rats by administration of these compounds into the third ventricle via a microdialysis probe. The results obtained add further support to the hypothesis that PGD2 is involved in the promotion ...