Awaking effect of PGE2 microinjected into the preoptic area of rats

Matsumura, Hitoshi; Goh, Yasumasa; Ueno, Ryuji; Sakai, Toshiaki; Hayaishi, Osamu

doi:10.1016/0006-8993(88)90935-3

Cited by 45 publications

(20 citation statements)

References 28 publications

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“…Lesion of the preoptic area suppresses sleep (28), electrical (17) or thermal stimulation (46) of the MPA increases sleep, and sleep deprivation induces c-fos expression in the MPA (44). Intra-MPA microinjection of adenosine agonist (55), TNF-␣ (23), and growth hormone-releasing hormone (68) enhances sleep, whereas prostaglandin E2 (27) and octreotide (16) induce arousal. Similar to ghrelin, microinjection of orexin-A into the MPA increases time spent awake (10).…”

Section: Discussionmentioning

confidence: 99%

Ghrelin microinjection into forebrain sites induces wakefulness and feeding in rats

Szentirmai¹,

Kapás²,

Krueger³

2007

American Journal of Physiology-Regulatory, Integrative and Comp

110

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Szentirmai É , Kapás L, Krueger JM. Ghrelin microinjection into forebrain sites induces wakefulness and feeding in rats. Am J Physiol Regul Integr Comp Physiol 292: R575-R585, 2007. First published August 17, 2006; doi:10.1152/ajpregu.00448.2006.-Ghrelin, a gutbrain peptide, is best known for its role in the stimulation of feeding and growth hormone release. In the brain, orexin, neuropeptide Y (NPY), and ghrelin are parts of a food intake regulatory circuit. Orexin and NPY are also implicated in maintaining wakefulness. Previous experiments in our laboratory revealed that intracerebroventricular injections of ghrelin induce wakefulness in rats. To further elucidate the possible role of ghrelin in the regulation of arousal, we studied the effects of microinjections of ghrelin into hypothalamic sites, which are implicated in the regulation of feeding and sleep, such as the lateral hypothalamus (LH), medial preoptic area (MPA), and paraventricular nucleus (PVN) on sleep in rats. Sleep responses, motor activity, and food intake after central administration of 0.04, 0.2, or 1 g (12, 60, or 300 pmol) ghrelin were recorded. Microinjections of ghrelin into the LH had strong wakefulness-promoting effects lasting for 2 h. Wakefulness was also stimulated by ghrelin injection into the MPA and PVN; the effects were confined to the first hour after the injection. Ghrelin's non-rapid-eye-movement sleepsuppressive effect was accompanied by attenuation in the electroencephalographic (EEG) slow-wave activity and changes in the EEG power spectrum. Food consumption was significantly stimulated after microinjections of ghrelin into each hypothalamic site. Together, these results are consistent with the hypothesis that forebrain ghrelinergic mechanisms play a role in the regulation of vigilance, possibly through activating the components of the food intake-and arousalpromoting network formed by orexin and NPY. lateral hypothalamus; medial preoptic area; paraventricular nucleus; electroencephalogram; slow-wave activity; sleep GHRELIN IS A 28-AMINO ACID peptide produced by endocrine cells in the gastrointestinal system and by neurons in the central nervous system (21). Circulating ghrelin is derived mainly from the stomach (1). Plasma ghrelin levels inversely correlate with feeding; fasting increases, while food intake reduces, plasma ghrelin concentrations (7, 61). In the brain, ghrelin is produced by arcuate nucleus (ARC) neurons and by a distinct hypothalamic neuronal population in the internuclear region (6). Ghrelin's actions are mediated by the growth hormone secretagogue receptor (GHS-R) (21). GHS-R mRNA is widely distributed in the gastrointestinal tract, sensory vagus fibers, and the brain. Those hypothalamic nuclei that are implicated in the regulation of feeding and/or sleep-wake activity, such as the lateral hypothalamus (LH), paraventricular nucleus (PVN), ARC, dorsomedial hypothalamic nucleus, anteroventral preoptic nucleus, anterior hypothalamic area, suprachiasmatic nucleus, anterolateral hypothalamic nucleus, and the...

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Section: Discussionmentioning

confidence: 99%

Ghrelin microinjection into forebrain sites induces wakefulness and feeding in rats

Szentirmai¹,

Kapás²,

Krueger³

2007

American Journal of Physiology-Regulatory, Integrative and Comp

110

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“…These results strongly indicate that PGE, may be one of the endogenous wakefulnesscontrolling factors that regulate the arousal systems in the TuM-PH of the mammalian brain. Intraventricular administration of PGE, strongly inhibits not only SWS but also REM sleep in rats (Matsumura et al, 1988). Further, cataplexy of the narcoleptic dog, a condition associated with the REM sleep disorders, was also inhibited by systemic…”

Section: Discussionmentioning

confidence: 93%

“…These thermosensitive neurons, especially the coldsensitive ones, have been shown to mediate the febrile response to PGE, induced by exogenous and endogenous pyrogens such as lipopolysaccharide and cytokines (Dinarello et al, 1988). Recent studies from our laboratory showed that PGE, promoted wakefulness when it was administered into the POA or third Onoe et al -Promotion of Wakeful ness by PGE, i n Posterior Hypothalamus ventricle of the rat (Matsumura et al, 1988(Matsumura et al, , 1989a) and suppressed sleep when it was infused into the lateral ventricle of the monkey (Onoe et al, 1988). In both cases, an intense febrile response occurred concomitantly with the PGE, administration.…”

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confidence: 97%

“…Peter G. Prostaglandins D, and E, (PGD,, PGE,) are the major arachidonic acid metabolites in neurons and glial cells of the mammalian brain (Narumiya et al, 1982;Ogorochi et al, 1984Ogorochi et al, ,1987Urade et al, 1987;Tsubokura et al, 1991). These PGs play roles in a variety of neurophysiological functions including the regulation of body temperature (Milton, 1976;Ueno et al, 1982), neuroendocrine function (Harms et al, 1973;Kinoshita et al, 1982), and sleep-wakefulness (Dzoijic, 1978;Ueno et al, 1982;InouC et al, 1984;Krueger, 1985;Matsumura et al, 1988;Onoe et al, 1988). Our previous results revealed that PGD,, acting as a sleep inducer, and PGE,, acting as a wakefulness promoter, jointly regulate the generation of sleep and wakefulness in the mammalian brain (Hayaishi, 1988, 199 1).…”

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confidence: 99%

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Prostaglandin E2 exerts an awaking effect in the posterior hypothalamus at a site distinct from that mediating its febrile action in the anterior hypothalamus

Onoe¹,

Watanabe²,

Ono³

et al. 1992

J. Neurosci.

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The precise sites for prostaglandin E2 (PGE2)-related activity responsible for the promotion of wakefulness and elevation of brain temperature were determined in several regions of the monkey brain. PGE2 was administered through a microdialysis probe into 11 brain loci mainly in the preoptic area/anterior hypothalamic region (POA/AH) and the tuberomammillary region in the posterior hypothalamus (TuM-PH). Administration of PGE2 into the POA/AH resulted in a marked and dose- dependent febrile response. When a low dose (15 pmol/min) of PGE2 was administered into the POA/AH, brain temperature increased significantly up to a 0.6 degrees C rise, but sleep behavior and amounts of time in wakefulness, slow wave sleep (SWS), and REM sleep during the administration period were not significantly different from those of the control monkeys. Dose of PGE2 above 150 pmol/min elevated the brain temperature and heart rate more markedly and suppressed sleep. The degree of inhibition of sleep by PGE2 was closely correlated with the changes in these autonomic responses. On the other hand, when a low dose of PGE2 was administered into the TuM-PH, the time spent awake during the administration period increased up to 3.5-fold and the amount of time spent in SWS decreased to 50% of that of the control level, with negligible changes in brain temperature and heart rate. The awaking response of PGE2 in the TuM-PH was also dose dependent, but was not correlated with the change in brain temperature. Among 11 brain regions tested, the hyperthermic effect of PGE2 was most potent in the POA, while its awaking effect was most pronounced in the TuM-PH close to the mammillary complex. These findings demonstrate that the site of action of PGE2 for the regulation of sleep-wakefulness is clearly distinct from that for the temperature regulation. PGE2 may be involved in the neurochemical mechanism of wakefulness mediated in a specific site in the PH.

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“…These mediators are natural constituents of the central nervous system (CNS) (14); metabolic pathways as well as specific receptors for PGs have been described in the brain (15-17). Furthermore, it has been demonstrated that CNS administration of PGD2 and PGE2, the two major prostaglandins in the mammalian CNS, respectively facilitates and inhibits sleep (18)(19)(20)(21)(22). As an alternative basis to the cholinergic and monoaminergic hypotheses, we explored the roles of PGD2 and PGE2 in canine narcolepsy.…”

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confidence: 99%

Prostaglandin E2 and its methyl ester reduce cataplexy in canine narcolepsy.

Nishino

Mignot

Fruhstorfer

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

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The effects of intravenous administration of prostaglandins (PGs) were investigated in genetically narcoleptic Doberman pinschers. The treatment of narcoleptic dogs with PGE2 and PGE2 methyl ester, but not PGD2 and PGD2 methyl ester, induced a dose-dependent reduction of canine cataplexy, a dissociated manifestation of rapid-eye-movement sleep. The effect was specific and not associated with any change in other behavior. Furthermore, the effect was longlasting (up to 2 hr) and could not be explained by the acute cardiovascular changes seen after intravenous PG administration. PGE2 methyl ester, a lipophilic derivative of PGE2 with more central penetration than PGE2, was 4 times more potent than PGE2. These results indicate that PGE2 modifies cataplexy through a central effect and suggest that this prostaglandin may play a role in rapid-eye-movement sleep regulation.Narcolepsy is a disabling sleep disorder of unknown etiology characterized by excessive daytime sleepiness and cataplexy (attacks of flaccid muscle paralysis occurring at the onset of increased emotion) (1). Sleep-recording studies in narcoleptic patients show an abnormally rapid transition from wake to rapid-eye-movement (REM) sleep during the day and an extremely shortened REM latency at night (1). Since a state of muscular paralysis similar to cataplexy normally occurs during REM sleep, narcolepsy is considered a REM sleep disorder (1). Canine narcolepsy is a spontaneous animal model presenting striking similarities to human narcolepsy both in its behavioral manifestation (i.e., cataplexy and sleepiness) and response to therapeutic drugs (2-6).Studies on the regulation of narcolepsy-cataplexy and REM sleep have emphasized cholinergic and monoaminergic hypotheses (4-10). However, the recent discovery that human narcolepsy is strongly associated with human leukocyte antigens DR2, Dw2, and DQwl (11) has led several investigators to propose an autoimmune etiology for this disorder (12). Prostaglandins (PGs) are intimately involved in inflammation and the immune response (13). These mediators are natural constituents of the central nervous system (CNS) (14); metabolic pathways as well as specific receptors for PGs have been described in the brain (15-17). Furthermore, it has been demonstrated that CNS administration of PGD2 and PGE2, the two major prostaglandins in the mammalian CNS, respectively facilitates and inhibits sleep (18)(19)(20)(21)(22). As an alternative basis to the cholinergic and monoaminergic hypotheses, we explored the roles of PGD2 and PGE2 in canine narcolepsy. Recently, methyl ester derivatives of PGs with more CNS penetration have been described, and the peripheral administration of these compounds has been used to better define the CNS effects of PGs (23,24). In this study, we administered PGD2, PGE2 and their methyl esters, PGD2-Me and PGE2-Me, to narcoleptic dogs and found that intravenous administration of PGE2-Me induced a dose-dependent reduction of cataplexy in canine narcolepsy. MATERIALS AND METHODSAnimals. Six gene...

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Awaking effect of PGE2 microinjected into the preoptic area of rats

Cited by 45 publications

References 28 publications

Ghrelin microinjection into forebrain sites induces wakefulness and feeding in rats

Ghrelin microinjection into forebrain sites induces wakefulness and feeding in rats

Prostaglandin E2 exerts an awaking effect in the posterior hypothalamus at a site distinct from that mediating its febrile action in the anterior hypothalamus

Prostaglandin E2 and its methyl ester reduce cataplexy in canine narcolepsy.

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