Systematic interactome mapping and genetic perturbation analysis of a C. elegans TGF-beta signaling network.

To initiate a system-level analysis of C. elegans DAF-7/TGF-beta signaling, we combined interactome mapping with single and double genetic perturbations. Yeast two-hybrid (Y2H) screens starting with known DAF-7/TGF-beta pathway components defined a network of 71 interactions among 59 proteins.

Effects of early undernutrition on the brain insulin-like growth factor-I system.

Undernutrition reduces circulating concentrations of insulin-like growth factor (IGF)-I, but how it affects the brain IGF system, especially during development, is largely unknown. We have studied IGF-I, IGF-II, IGF receptor and IGF binding protein (BP)-2 mRNA expression in the hypothalamus, cerebellum and cerebral cortex of neonatal rats that were food restricted beginning on gestational day 16. One group was refed starting on postnatal day 14.

Circulating insulin-like growth factor I mediates the protective effects of physical exercise against brain insults of different etiology and anatomy.

Physical exercise ameliorates age-related neuronal loss and is currently recommended as a therapeutical aid in several neurodegenerative diseases. However, evidence is still lacking to firmly establish whether exercise constitutes a practical neuroprotective strategy. We now show that exercise provides a remarkable protection against brain insults of different etiology and anatomy.

Circulating insulin-like growth factor I mediates effects of exercise on the brain.

Physical exercise increases brain activity through mechanisms not yet known. We now report that in rats, running induces uptake of blood insulin-like growth factor I (IGF-I) by specific groups of neurons throughout the brain. Neurons accumulating IGF-I show increased spontaneous firing and a protracted increase in sensitivity to afferent stimulation.

Neurodegeneration is associated to changes in serum insulin-like growth factors.

Serum levels of insulin and insulin-like growth factors and their binding proteins (IGFs and IGFBPs, respectively) are changed in human neurodegenerative diseases of very different etiology, such as Alzheimer's disease, amyotrophic lateral sclerosis, or cerebellar ataxia. However, the significance of these endocrine disturbances is not clear. We now report that in two very different inherited neurodegenerative conditions, ataxia-telangiectasia (AT) and Charcot-Marie-Tooth 1A (CMT-1A) disease, serum levels of IGFs are also altered.

Anatomically specific changes in the expression of somatostatin, growth hormone-releasing hormone and growth hormone receptor mRNA in diabetic rats.

Growth hormone (GH) secretion is altered in poorly controlled diabetic animals. However, modifications in the hypothalamic neuropeptides that control GH secretion, somatostatin and GH-releasing hormone (GHRH), as well as changes in the sensitivity of the hypothalamus and pituitary to the feedback effects of GH, are less clear. We have used RNase protection assays and in-situ hybridization to address whether the mRNA expression of GH, somatostatin and GHRH, as well as of the GH receptor (GHR) in the hypothalamus and anterior pituitary, are altered in streptozotocin-induced diabetic rats.

Specific alterations of the insulin-like growth factor I system in the cerebellum of diabetic rats.

Specific changes in circulating levels of insulin-like growth factor I (IGF-I) and various IGF-binding proteins are known to occur in insulin-dependent diabetic patients and laboratory animals. However, little attention has been paid to the effects of this chronic metabolic disease on the IGF system of the central nervous system. Because various types of human cerebellar degeneration are accompanied by changes in the peripheral IGF-I system which are similar, although not identical, to those found in diabetes, we tested whether diabetes results in changes in the cerebellar IGF-I system.

The role of glia in the neuroendocrine hypothalamus: possible implications in hormone secretion.

Recent evidence indicates that glia may play a significant role in the link between the endocrine and nervous systems. Gonadal steroids modulate astroglia morphology, differentiation and gene expression in different brain areas. Hormonal effects on glia may have important consequences for neuronal development, metabolism and activity, for the formation and plasticity of synaptic connections, and for the modulation of hypothalamic hormone release.

Sexual dimorphism and sex steroid modulation of glial fibrillary acidic protein messenger RNA and immunoreactivity levels in the rat hypothalamus.

By using the techniques of in situ hybridization histochemistry and immunocytochemistry, we have found that both glial fibrillary acidic protein messenger RNA levels and glial fibrillary acidic protein immunoreactive surface density in the arcuate nucleus and median eminence are modulated by both the neonatal and adult sex steroid environments. No effect was seen on the number of immunoreactive glia. Intact adult males had significantly higher glial fibrillary acidic protein messenger RNA levels and glial fibrillary acidic protein immunoreactive surface density than females.

Insulin-like growth factor I is an afferent trophic signal that modulates calbindin-28kD in adult Purkinje cells.

Recent evidence suggests that Purkinje cells are specific targets of insulin-like growth factor I (IGF-I) through their entire life span. During development, Purkinje cell numbers and their calbindin-28kD content increase after IGF-I treatment in culture. In the adult, part of the IGF-I present in the cerebellum is transported from the inferior olive, and modulates Purkinje cell function.

Gonadal hormone regulation of neuronal-glial interactions in the developing neuroendocrine hypothalamus.

Recent evidence indicates that, in addition to their well known effects on neurons, gonadal steroids may exert part of their neural effects through astroglia. In adult female rats astroglia participate in the phasic remodelling of synapses that takes place during the estrous cycle in the arcuate nucleus of the hypothalamus under the influence of estradiol. Astroglia also appear to be involved in the genesis of sex differences in synaptic connectivity.