title: Prostaglandin E2 mediates cellular effects of interleukin-1beta on parvocellular neurones in the paraventricular nucleus of the hypothalamus.
abstract: Abstract Interleukin-1beta (IL-1beta) is involved in hypothalamic regulation of corticotrophin-releasing hormone secretion, autonomic activation and consequent downstream modulation of the neuroimmune response. Previously, we have shown that IL-1beta depolarises parvocellular neurones in the paraventricular nucleus (PVN) of the hypothalamus, and these effects are dependent on attenuation of gamma-amino butyric acid (GABA)-ergic input. In the present study, using whole-cell patch clamp recordings of rat neurones in a slice preparation of the PVN, we show that the effects of IL-1beta are abolished in the presence of a cyclooxygenase (COX)-2 inhibitor, NS-398, indicating a dependence on prostaglandin (PG) synthesis and activation. In response to 1 microM PGE2, 64% of parvocellular neurones tested exhibited a clear depolarisation, which was abolished in the presence of tetrodotoxin (TTX). Furthermore, neurones responsive to both IL-1beta and PGE2 exhibited a decrease in the frequency of inhibitory post-synaptic potentials, suggesting that effects of these modulators are mediated via a decrease in GABA-ergic input to these neurones. A proportion (44% and 40%, respectively) of putative GABA-ergic neurones in the halo region surrounding the PVN demonstrated hyperpolarising responses to 1 nM IL-1beta and 1 microM PGE2, and these effects were maintained in TTX. Furthermore, direct hyperpolarising effects of IL-1beta were blocked in the presence of NS-398. Together, these data suggest that PGE2, synthesised in response to IL-1beta-activation of COX-2 expressing cells, directly hyperpolarises putative GABA-ergic neurones in the halo zone surrounding and projecting to the PVN, resulting in a decrease in GABA-ergic input to parvocellular neurones and consequent depolarisation. These data further elucidate the cellular mechanisms by which IL-1beta exerts its neuroimmune-related actions in the PVN.
authors: Department of Physiology, Queen's University, Kingston, Ontario, Canada.
authors: C C
authors: CC
authors: Ferri
authors: A V
authors: AV
authors: Ferguson
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D015232:Dinoprostone / Q000502:physiology*; D007375:Interleukin-1 / Q000378:metabolism*; D008297:Male; D009415:Nerve Net / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D007375:Interleukin-1; D005680:gamma-Aminobutyric Acid; D015232:Dinoprostone