Ecdysteroid receptors located in the central nervous system of an insect

Summary Using thaw-mount autoradiography for steroid hormones, we obtained direct evidence for a nuclear localization of ecdysteroid binding sites in target organs of blowfly (Calliphora vicina) larvae. The binding sites revealed properties of ecdysteroid receptors. Endocrine cells of the ring gland were found to be target tissues of ecydysteroids. This observation provides morphological evidence for a network of complex interendocrine regulation. In the central nervous system receptorcontaining neurons were identified which include many, if not all, neurosecretory cells of the brain. A map of ecdysteroid sensitive cells of the larval brain is presented.     

Neuronal and glial markers of the central nervous system

Summary This brief review evaluates the expression of cell-specific markers on differentiated neural cells and, where necessary, on their developing precursors. Within these limitations only the commonly used markers are discussed and those deemed unequivocal are only briefly appraised.     

The role of the autonomic nervous system in mediating pancreatic endocrine responses to arginine in the calf

Summary The release of insulin which occurred in response to arginine, in the conscious calf, differed from that which occurs in response to glucose in that it was not significantly affected by either adrenergic or muscarinic blocking agents. Release of pancreatic glucagon was reduced by pretreatment with phentolamine.This work was supported by the British Diabetic Association. It is a particular pleasure to acknowledge the skilled assistance provided by Messrs P. M. M. Bircham and G. P. McGregor.     

The role of apolipoprotein E in lipid metabolism in the central nervous system

The critical roles of apolipoprotein E (apoE) in regulating plasma lipid and lipoprotein levels have been extensively studied for over 2 decades. However, an understanding of the roles of apoE in the central nervous system (CNS) is less certain. This review will summarize the available experimental results on the role of apoE in CNS lipid homeostasis with respect to its modulation of sulfatide trafficking, alteration of CNS cholesterol homeostasis and apoE-induced changes in phospholipid molecular species in specialized subcellular membrane fractions. The results indicate that apoE mediates sulfatide trafficking and metabolism in the CNS. Moreover, although apoE does not affect the cholesterol mass content or the phospholipid mass levels and composition in the CNS as a whole, apoE modulates cholesterol and phospholipid homeostasis in selective subcellular membrane compartments. Through elucidating the roles of apoE in CNS lipid metabolism, new insights into overall functions of apoE in neurobiology can be accrued ultimately, leading to an increased understanding of CNS lipid metabolism and the identification of novel therapeutic targets for CNS diseases.Received 9 January 2004; received after revision 28 February 2004; accepted 10 March 2004     

Stereological analysis of lipofuscin in the central nervous system ofTorpedo marmorata: correlation with superoxide dismutase distribution

Summary It was observed that superoxide dismutase activity was inversely proportional to the amount of lipofuscin present in the various anatomotopographical areas of theTorpedo marmorata central nervous system. These results support the theory that age pigments are a product of free lipoperoxidation induced by free radicals.Part of the present work was presented at XIIth Int. Pigment Cell Conference, Giessen (FRG), 17–19 September 1983.     

The potential therapeutic role of statins in central nervous system autoimmune disorders

3-Hydroxy-3-methyglutaryl coenzyme A (HMG-CoA) reductase inhibitors, statins are widely used oral cholesterol-lowering drugs. Statins competitively inhibit HMG-CoA reductase, the enzyme that catalyzes conversion of HMG-CoA to L-mevalonate, a key intermediate in cholesterol synthesis. Certain metabolites of mevalonate are also involved in posttranslational modification of specific proteins involved in cell proliferation and differentiation. Thus, statins have important biologic effects that may be independent of their cholesterol-reducing properties. Recent studies indicate that statins have antiinflammatory and neuroprotective properties which may be beneficial in the treatment of multiple sclerosis as well as other central nervous system (CNS) neurodegenerative diseases. This article will outline current experimental evidence that may suggest potential clinical benefits for patients with CNS autoimmune disorders. Ultimately, clinical trials will have to determine the safety and efficacy of statins in this patient population.Received 17 April 2003; received after revision 21 May 2003; accepted 22 May 2003     

Regulation of nicotinic acetylcholine receptors by tyrosine kinases in the peripheral and central nervous system: same players, different roles

Nicotinic acetylcholine receptors (nAChRs) exist in many subtypes and are found in the peripheral and central nervous system where they mediate or modulate synaptic transmission. We review how tyrosine phosphorylation and kinases regulate muscle and neuronal nAChRs. Interestingly, although some of the same kinase players interact with the various receptor subtypes, the functional consequences are different. While concerted action of MuSK, Abl- and Src-family kinases (SFKs) regulates the synaptic distribution of nAChRs at the neuromuscular junction, SFKs activate heteromeric neuronal nAChRs in adrenal chromaffin cells, thereby enhancing catecholamine secretion. In contrast, the activity of homomeric neuronal nAChRs, as found in the hippocampus, is negatively regulated by tyrosine phosphorylation and SFKs. It appears that tyrosine kinases provide the means to regulate all nAChRs; but the functional consequences, even those caused by the same kinase family, are specific for each receptor subtype and location. Received 21 February 2006; received after revision 24 July 2006; accepted 30 August 2006     

The specification of neuronal identity in the mammalian cerebral cortex

Summary The determination of neuronal fate in the developing cerebral cortex has been studied by tracking normal cell lineages in the cortex, and by testing the commitment of young cortical neurons to their normal fates. These studies together suggest that neuronal progenitors are multipotent during development and have the potential to produce neurons destined for many or all of the cortical layers. However, the laminar identity of an individual neuron appears to be specified through environmental interactions at the time of the cell's temrinal mitotic division, prior to its migration into the cortical plate.     

The role of growth hormone and insulin-like growth factors in the immune system

Growth hormone (GH) and insulin-like growth factor I (IGF-I) can modulate the development and function of the immune system. In this chapter, we present data on the expression of receptors for GH and IGFs and the in vitro and in vivo effects of these proteins. We show that expression of GH and IGFs in the immune system opens up the possibility that these proteins are not only involved in endocrine control of the immune system but can also play a role as local growth and differentiation factors (cytokines). Endocrine control of GH could be direct or mediated via endocrine or autocrine/paracrine IGF-I. In addition, GH can act as an autocrine or paracrine factor itself. Furthermore, IGF-I in the immune system has been shown to be regulated by cytokines, such as interleukin-1 and interferon-γ, alluding to a cytokine-like function of IGF-I. In addition to data on the function of GH and IGF-I in the immune system, we present new findings which imply a possible function of IGF-II and IGF-binding proteins.     

Central role of dendritic cells in the regulation and deregulation of immune responses

Dendritic cells (DCs) play a critical role in orchestrating the innate and adaptive components of the immune system so that appropriate, coordinated responses are mounted against infectious agents. Tissue-resident DCs interact with microbes through germline-encoded pattern-recognition receptors (PRRs), which recognize molecular patterns expressed by various microorganisms. Antigens use PRR activation to instruct DCs for the appropriate priming of natural killer (NK) cells, followed by specific T-cell responses. Due to the central role of DCs in regulating the activation and progression of immune responses, minor imbalances in the feedback control of Toll-like receptor (TLR)-activated cells have been associated with autoimmunity in genetically prone individuals. We review here recent findings on the role of DCs in the priming of innate and adaptive immune responses and the possible involvement of DCs in inducing and maintaining autoimmune reactions.     

Involvement of H1 receptors in the central antinociceptive effect of histamine: Pharmacological dissection by electrophysiological analysis

Intracerebroventricular (i.c.v.) administration of histamine (HA, 0.025–0.1 M/rat) to arthritic rats induces a dose-related inhibition of the neuronal thalamic firing evoked by peripheral noxious stimuli. To characterize the type(s) of HA receptors involved in this depressing activity of the amine we used electrophysiological techniques to examine the effects of i.c.v. administration of H₁ and H₂ agonists and antagonists on the spontaneous and evoked nociceptive firing of the thalamic neurons in rats rendered arthritic by Freund's adjuvant. The H₁ agonist 2-pyridylethylamine (0.4–1.0 M/rat, i.c.v) displayed a dose-dependent antinociceptive effect very similar to that of HA, while the H₂ agonist dimaprit (0.05–0.2 M/rat, i.c.v.) did not modify thalamic firing. Neither mepyramine (H₁ antagonist, 0.1 M/rat, i.c.v.) nor zolantidine (H₂ antagonist, 0.01 M/rat, i.c.v.) modified the evoked firing of rat thalamic neurons. When administered before HA (0.1 M/rat, i.c.v.) mepyramine but not zolantidine was able to inhibit the antinociceptive effect of HA. On the basis of the present electrophysiological results, we suggest that a specific interaction of histamine with H₁ receptors may be important for its antinociceptive effect on afferent peripheral inputs to the thalamus.     

The expression profile of TLR9 mRNA and CpG ODNs immunostimulatory actions in the teleost gilthead seabream points to a major role of lymphocytes

The potential effects of synthetic unmethylated oligodeoxynucleotides (ODN) containing CpG motifs, mimicking bacterial DNA, has never been evaluated on the immune response in the teleost fish gilthead seabream (Sparus aurata), the most important fish species in Mediterranean aquaculture. First, binding and competition studies have demonstrated that binding is saturated and promiscuous, suggesting the participation of several receptors. Moreover, leucocyte cytotoxic (NCC) activity, production of ROIs (reactive oxygen intermediates), and expression of immune-relevant genes was greatly primed by ODNs. Focusing on the mechanism, the TLR9 gene is widely distributed in seabream tissues and differently regulated in vitro by several stimuli. Moreover, and for the first time in fish, TLR9 mRNA has been detected in lymphocytes as the main cell-source. To conclude, ODNs containing GACGTT, GTCGTT (optimal for mouse and human, respectively) or AACGTT motifs are the most potent inducers of seabream immunity, whilst the involvement of TLR9 is under debate.     

The <Emphasis Type="Italic">Adhesion</Emphasis> GPCRs: A unique family of G protein-coupled receptors with important roles in both central and peripheral tissues

G protein-coupled receptors (GPCRs) are a diverse superfamily of membrane-bound receptors. The second largest subgroup of GPCRs, the Adhesion GPCRs, has 33 members in humans. Phylogenetic analysis of the entire repertoire of the seven transmembrane- domain (7TM) regions of GPCRs shows that the Adhesion GPCRs form a distinct family. Adhesion GPCRs are characterised by (1) long N termini with multiple functional domains often found in other proteins such as tyrosine kinases, integrins and cadherins, (2) highly complex genomic structure with multiple introns and splice variants and (3) a 7TM region that has no clear similarities with 7TM from other GPCRs. Several Adhesion GPCRs are known to have a role in the immune system but it is becoming more evident that many have important roles in the CNS. We speculate that the overall structural construction of the Adhesion GPCRs allows them to participate in different types of cell guidance. Received 8 February 2007; received after revision 21 March 2007; accepted 25 April 2007     

Steroid hormones and the cardiovascular system: Direct actions of estradiol,progesterone, testosterone,gluco- and mineralcorticoids,and soltriol [vitamin D] on central nervous regulatory and peripheral tissues

Summary Knowledge of steroid hormone sites of action and related effects in cardiovascular and neural regulatory tissues is reviewed. Evidence for nuclear receptor sites is derived mainly from autoradiographic studies with relatively intact tissues and some biochemical studies with tissue homogenates.In the heart and in the walls of blood vessels, estradiol, dihydrotestosterone, corticosterone, aldosterone, dexamethasone, and soltriol (vitamin D) show nuclear binding. In the brain and spinal cord, neuronal regions associated with cardiovascular regulation contain nuclear receptors in specific patterns for each steroid hormones, including progesterone and soltriol. These data indicate that all steroid hormones exert direct actions on the cardiovascular system at its different levels of organization, thus enabling adjustment to the changing demands during reproduction (gonadal steroids), stress (adrenal steroids), and solar seasons (vitamin D-soltriol).