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Prostaglandin E 2 Mediates Cellular Effects of Interleukin‐1β on Parvocellular Neurones in the Paraventricular Nucleus of the Hypothalamus
Author(s) -
Ferri C. C.,
Ferguson A. V.
Publication year - 2005
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/j.1365-2826.2005.01336.x
Subject(s) - medicine , endocrinology , parvocellular cell , tetrodotoxin , hypothalamus , chemistry , nucleus , prostaglandin e , inhibitory postsynaptic potential , prostaglandin e2 , biology , neuroscience
Interleukin‐1β (IL‐1β) 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‐1β depolarises parvocellular neurones in the paraventricular nucleus (PVN) of the hypothalamus, and these effects are dependent on attenuation of γ‐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‐1β 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 µ M PGE 2 , 64% of parvocellular neurones tested exhibited a clear depolarisation, which was abolished in the presence of tetrodotoxin (TTX). Furthermore, neurones responsive to both IL‐1β and PGE 2 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 n M IL‐1β and 1 µ M PGE 2 , and these effects were maintained in TTX. Furthermore, direct hyperpolarising effects of IL‐1β were blocked in the presence of NS‐398. Together, these data suggest that PGE 2 , synthesised in response to IL‐1β‐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‐1β exerts its neuroimmune‐related actions in the PVN.