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

Abstract

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.

Neural circuitry engaged by prostaglandins during the sickness syndrome

“…Infusion of PGE2 in the TMN markedly increases wakefulness 61 . In addition, TMN neurons express EP4 receptors, and infusion of an EP4 agonist in this region increases histamine release and wakefulness 62 .…”

Prostaglandin involvement in hyperthermia induced by sleep deprivation: A pharmacological and autoradiographic study

“…Accumulating evidence suggests that prostaglandins (PG) have numerous and diverse biological effects on a wide variety of physiological activities, including a modulatory effect on both thermoregulation and sleep body temperature (Wolfe, 1982;Onoe et al,1992). PGE2, the dominant form of endogenous E-series prostaglandins (PGE), is produced in the brain in response to exogenous and endogenous pyrogens and seems to be the crucial neuronal mediator of fever in the brain through an action on PG receptor-expressing neurons in the preoptic area (POA) of the anterior hypothalamus (Milton, 1982).…”

A Novel Subtype of the Prostacyclin Receptor Expressed in the Central Nervous System

“…For example, PGD 2 acts as a sleep inducer (1,2), produces hypothermia (3), inhibits luteinizing hormone-releasing hormone release (4), and is involved in biphasic modulation of pain sensation (5) and modification of olfaction (6). PGE 2 has hyperthermic (7), sedative (8), anticonvulsive (9,10), and antidiuretic effects (11) and induces wakefulness (12,13), stimulates luteinizing hormone-releasing hormone release (14), modifies pain (5,9), and regulates food intake (11). Also, PGF 2␣ has an antidiuretic effect (15) and an inhibitory effect on oxytocin release (16).…”