Interleukin-1 mediates the anorexic and febrile actions of galanin-like Peptide.

Galanin-like peptide (GALP) is a neuropeptide that has complex actions on energy balance, producing orexigenic effects in the short term in rats but anorexigenic and febrile effects over the longer term in rats and mice. GALP is thought to promote feeding via neuropeptide Y and orexin neurons, but the mediators of the anorexia are unknown. However, the anorexic and febrile actions of GALP are similar in magnitude and profile to those seen after central injections of the cytokine IL-1. Thus, the aim of this study was to test the hypothesis that IL-1 mediates the effects of GALP on energy balance. Intracerebroventricular injection of GALP (1.5 nmol) in male Sprague-Dawley rats stimulated production of IL-1alpha and IL-1beta protein in macrophages and/or microglia in selected brain areas, including the meninges, and periventricular brain regions. Intracerebroventricular injection of GALP in rats stimulated food intake over 1 h but decreased feeding and body weight at 24 h and caused a rise in core body temperature over 8 h. Coinfusion of the IL-1 receptor antagonist had no effect on the GALP-induced orexigenic response but significantly reduced the longer-term actions of GALP observed at 24 h and its effect on body temperature. Furthermore, the actions of GALP on feeding, body weight, and body temperature were significantly reduced in IL-1alpha/beta-, IL-1beta-, or IL-1 type I receptor (IL-1RI)-deficient mice. These data suggest that GALP induces expression of IL-1 in the brain, and its anorexic and febrile actions are mediated by this cytokine acting via IL-1 type I receptor.

Galanin-like peptide: a role in the homeostatic regulation of energy balance?

Galanin-like peptide (GALP) is a neuropeptide that has been proposed to play a role in the regulation of food intake behaviour and body weight. However, the actions of GALP on energy balance are complex. In rats, it appears to impel both appetite stimulating and suppressing effects, whereas in mice, the only effect is a reduction in food intake. Thus, it is currently unclear whether GALP is important in the homeostatic regulation of energy balance, or if it produces effects on appetite and body weight by non-specific actions. This review discusses current evidence of the role of GALP with respect to energy balance, and the mechanisms involved in its regulation. We describe recent evidence that suggests that GALP may elicit differential effects in different rodent species. Furthermore, we provide an insight into a potential novel role for GALP in inflammation, and discuss how this may relate to the non-homeostatic regulation of energy balance.

Pineal gland expression of the transcription factor Egr-1 is restricted to a population of glia that are distinct from nestin-immunoreactive cells.

Egr-1 is a plasticity-related transcription factor that has been implicated in circadian regulation of the pineal gland. In the present study we have investigated the cellular expression pattern of Egr-1 in the adult rat pineal. Egr-1 protein is restricted to the nucleus of a sub-population of cells. These cells were characterised using a new transgenic rat model (egr-1-d2EGFP) in which green fluorescent protein is driven by the egr-1 promoter. Cellular filling by GFP revealed that Egr-1-positive cells exhibited processes, indicating a glial cell-type morphology. This was confirmed by co-localizing the GFP-filled processes with vimentin and S-100beta. However, GFP/Egr-1 is expressed in only a tiny minority of the previously identified Id-1/vimentin-positive glial cells and therefore represents a novel sub-set of this (GFAP-negative) glial population. We have also demonstrated for the first time an extensive network of nestin-positive cells throughout the adult pineal gland, however these cells do not co-express Egr-1. Our studies have therefore broadened our understanding of the cell populations that constitute the adult pineal. Cellular localization of Egr-1 has revealed that this factor does not appear to be directly involved in pinealocyte production of melatonin but is required in a sub-set of pineal glia.

Cellular distribution of Egr1 transcription in the male rat pituitary gland.

The transcription factor gene Egr1 is necessary for female fertility; EGR1 protein is an established molecular regulator of adult female gonadotroph function where it mediates GNRH-stimulated transcription of the Lhb gene. Recent studies have also implicated pituitary EGR1 in the mediation of other physiological signals indicating an integrative function. However, the role of EGR1 in males is less well defined and this uncertainty is compounded by the absence of cellular expression data in the male pituitary gland. The aim of this study, therefore, was to define the distribution of Egr1 gene expression in the adult male rat pituitary. To further this aim, we have evaluated cellular populations in a transgenic rat model (Egr1-d2EGFP), in which we demonstrate regulated green fluorescent protein (GFP) expression in EGR1+ pituitary cells. Cellular filling by GFP enabled morphological and molecular differentiation of different populations of gonadotrophs; Egr1 transcription and LHB were highly co-localised in a major population of large cells but only minimally co-localised in small GFP+ cells; the latter cells were shown to be largely (80%) composed of minority populations of GH+ somatotrophs (9% of total GH+) and PRL+ lactotrophs (3% of total PRL+). Egr1 transcription was not found in TSH+, ACTH+ or SOX2+ precursor cells and was only minimally co-localised in S-100ß+ folliculostellate cells. Our demonstration that the Egr1 gene is actively and selectively transcribed in a major sub-population of male LHB+ cells indicates a largely conserved role in gonadotroph function and has provided a basis for further defining this role.