| First Author | Tabarean IV | Year | 2006 |
| Journal | Neuroscience | Volume | 141 |
| Issue | 4 | Pages | 1685-95 |
| PubMed ID | 16777343 | Mgi Jnum | J:113156 |
| Mgi Id | MGI:3664684 | Doi | 10.1016/j.neuroscience.2006.05.007 |
| Citation | Tabarean IV, et al. (2006) Interleukin-1beta induces hyperpolarization and modulates synaptic inhibition in preoptic and anterior hypothalamic neurons. Neuroscience 141(4):1685-95 |
| abstractText | Most of the inflammatory effects of the cytokine interleukin 1beta (IL-1beta) are mediated by induction of cyclooxygenase (COX)2 and the subsequent synthesis and release of prostaglandin E2. This transcription-dependent process takes 45-60 min, but IL-1beta, a well-characterized endogenous pyrogen also exerts faster neuronal actions in the preoptic area/anterior hypothalamus. Here, we have studied the fast (1-3 min) signaling by IL-1beta using whole-cell patch clamp recordings in preoptic area/anterior hypothalamus neurons. Exposure to IL-1beta (0.1-1 nM) hyperpolarized a subset ( approximately 20%) of preoptic area/anterior hypothalamus neurons, decreased their input resistance and reduced their firing rate. These effects were associated with an increased frequency of bicuculline-sensitive spontaneous inhibitory postsynaptic currents and putative miniature inhibitory postsynaptic currents, strongly suggesting a presynaptic mechanism of action. These effects require the type 1 interleukin 1 receptor (IL-1R1), and the adapter protein myeloid differentiation primary response protein (MyD88), since they were not observed in cultures obtained from IL-1R1 (-/-) or from MyD88 (-/-) mice. Ceramide, a second messenger of the IL-1R1-dependent fast signaling cascade, is produced by IL-1R1-MyD88-mediated activation of the neutral sphingomyelinase. C2-ceramide, its cell penetrating analog, also increased the frequency of miniature inhibitory postsynaptic currents in a subset of cells. Both IL-1beta and ceramide reduced the delayed rectifier and the A-type K(+) currents in preoptic area/anterior hypothalamus neurons. The latter effect may account in part for the increased spontaneous inhibitory postsynaptic current frequency as suggested by experiments with the A-type K(+) channel blockers 4-aminopyridine. Taken together our data suggest that IL-1beta inhibits the activity of preoptic area/anterior hypothalamus neurons by increasing the presynaptic release of GABA. |
