Cholesterol homeostasis and function in neurons of the central nervous system

Cholesterol is a multifaceted molecule. First, it serves as an essential membrane component, as a cofactor for signaling molecules and as a precursor for steroid hormones; second, its synthesis, intercellular transport and intracellular distribution present a logistic tour de force requiring hundreds of cellular components, and third, it plays a crucial role in major human diseases. Despite intense research on this molecule, its metabolism in the central nervous system and its role in neuronal development and function are not well understood. Here I summarize recent results and hypotheses about how neurons maintain their cholesterol level and how cholesterol influences the establishment and maintenance of synaptic connections.     

High molecular weight FGF2: the biology of a nuclear growth factor

Fibroblast growth factor 2 (FGF2) is one of the most studied growth factors to date. Most attention has been dedicated to the smallest, 18kDa FGF2 variant that is released by cells and acts through activation of cell-surface FGF-receptor tyrosine kinases. There are, however, several higher molecular weight (HMW) variants of FGF2 that rarely leave their producing cells, are retained in the nucleus and act independently of FGF-receptors (FGFR). Despite significant evidence documenting the expression and intracellular trafficking of HMW FGF2, many important questions remain about the physiological roles and mechanisms of action of HMW FGF2. In this review, we summarize the current knowledge about the biology of HMW FGF2, its role in disease and areas for future investigation. Received 28 July 2008; received after revision 18 August 2008; accepted 22 August 2008     

The presence of monoamines in the nervous system ofPeripatopsis (Onychophora)

Summary Preliminary observations of formaldehyde-induced fluorescence support the suggestion that monoamines such as noradrenaline, dopamine and 5-hydroxytryptamine are transmitter agents in the central nervous system of Onychophora.Acknowledgments. We wish to thank Dr M. Fillenz for valuable advice and for generously enabling this work to be carried out, and we are indebted to Dr V. van der Lande for material.     

Seasonal monoamine changes in the central nervous system ofMytilus edulis (Bivalvia)

Summary The levels of serotonin, dopamine and norepinephrine exhibit seasonal changes in the central nervous system of Mytilus edulis. These monoamines were higher during the summer and lower during the winter.     

Interaction of serotonin and lysergic acid diethylamide (LSD) in the central nervous system

Zusammenfassung Serotonin (5-Oxytryptamin) wirkt bei der Maus als mildes Sedativum und steigert den hypnotischen Effekt von Evipan deutlich. Diese Wirkungssteigerung kann durch Lysergsäure-diäthylamid (LSD) antagonisiert werden. Dieser Befund stimmt mit der Ansicht überein, dem Serotonin komme eine physiologische Rolle im Gehirn zu und dass LSD möglicherweise durch antagonistische Wirkung gegenüber Serotonin Psychose verursachen kann.     

Suppression of pupal esterase activity in Aedes aegypti (Diptera: Culicidae) by an insect growth regulator.

Changes in non-specific esterases of Aedes aegypti were noted during pupal development. One esterase band was found to increase markedly within 3 h of pupation and this increase in activity was suppressed by prior treatment of larvae with an insect growth regulator, ZR 515. It is suggested that the esterase activity may help to reduce endogenous levels of juvenile hormone during metamorphosis and that the growth regulator may prevent this normal regulation.     

Preliminary results on the action of a plant growth regulator (Ethrel) in reducing the attack ofPrays oleae Bern. on olive fruits

Summary Preliminary experiments carried out in the Granada province of Southern spain over three years and in three different habitats have shown that a single application of Ethrel (2 chloro-ethyl phosphonic acid) to the olive tree at the beginning of fruit formation is sufficient to reduce significantly attack byPrays oleae Bern. and subsequent damage to the fruit. At the same time the treatment did not cause any detrimental change to the trees and had no measurable effect on the activity of beneficial insects such as Chrysopids (Neuroptera), which are known to be importantP. oleae egg predators in the study area.     

Activity of the principal alkaloids of Polyalthia oliveri Engler (Annonaceac) on the central nervous system and the cardiovascular system]

Polyalthia oliveri leaf alkaloid, oliveroline, shows in Mice antiparkinsonian properties which decrease or disappear with the alkalo?ds extracted from the bark of the trunk, oliveridine and oliverine. The latter alkaloid has an antihypertensive effect which is not found in oliveridine, only hypotensive by a relaxant close to papaverine action on vascular smooth muscles.     

The Arp2/3 complex: a central regulator of the actin cytoskeleton

In recent years the Arp2/3 complex has emerged as a central regulator of actin dynamics, assembling and cross-linking actin filaments to produce a diverse array of cellular structures. Here I discuss our current state of knowledge about this actin-remodelling machine. The predicted structure of the Arp2/3 complex can be directly correlated with its ability to nucleate, cap and cross-link actin filaments. A growing family of Arp2/3 complex activators such as the WASP family, type I myosins, and the newly identified activators cortactin and Abp1p tightly regulate this activity within the cell. Localised activation of the Arp2/3 complex produces structures such as lamellipodia or actin patches via a process termed dendritic nucleation. Furthermore, several pathogenic microorganisms have evolved strategies to 'hijack' the Arp2/3 complex to their own advantage. Finally, I discuss some of the questions which remain unanswered about this fascinating complex. Received 2 April 2001; received after revision 15 May 2001; accepted 18 May 2001     

The nucleotide receptor P2Y13 is a key regulator of hepatic High-Density Lipoprotein (HDL) endocytosis

Cell surface receptors for high-density lipoprotein (HDL) on hepatocytes are major partners in the regulation of cholesterol homeostasis. We recently identified a cell surface ATP synthase as a high-affinity receptor for HDL apolipoprotein A-I (apoA-I) on human hepatocytes. Stimulation of this ectopic ATP synthase by apoA-I triggered a low-affinity-receptor-dependent HDL endocytosis by a mechanism strictly related to the generation of ADP. This suggests that nucleotide G-protein- coupled receptors of the P2Y family are molecular components in this pathway. Only P2Y₁ and P2Y₁₃ are present on the membrane of hepatocytes. Using both a pharmacological approach and small interference RNA, we identified P2Y₁₃ as the main partner in hepatic HDL endocytosis, in cultured cells as well as in situ in perfused mouse livers. We also found a new important action of the antithrombotic agent AR-C69931MX as a strong activator of P2Y₁₃-mediated HDL endocytosis. Received 9 May 2005; received after revision 24 June 2005; accepted 1 September 2005