G protein-coupled receptor signalling in astrocytes in health and disease: A focus on metabotropic glutamate receptors

Work published over the past 10–15 years has caused the neuroscience community to engage in a process of constant re-evaluation of the roles of glial cells in the mammalian central nervous system. Recent emerging evidence suggests that, in addition to carrying out various homeostatic functions within the CNS, astrocytes can also engage in a two-way dialogue with neurons. Astrocytes possess many of the receptors, and some of the ion channels, present in neurons endowing them with an ability to sense and respond to an array of neuronal signals. In addition, an expanding number of small molecules and proteins have been shown to be released by astrocytes in both health and disease. In this commentary we will highlight advances in our understanding of G protein-coupled receptor signalling in astrocytes, with a particular emphasis on metabotropic glutamate (mGlu) receptors. Discussion will focus on the major mGlu receptors expressed in astrocytes, mGlu3 and mGlu5, how these receptors can influence different aspects of astrocyte physiology, and how signalling by these G protein-coupled receptors might change under pathophysiological circumstances

Origins of the educational system of Southern Rhodesia

A chronicle of the origins of the educational system of Southern Rhodesia (now Zimbabwe.)In april 1899 Rhodes gave advice to W. H. Milton on the formulation of the first Rhodesian Education Ordinance and predicted rightly, that what was decided on then would ‘practically be the educational system of the country in the future’; the genesis of this Ordinance (No. 18 of 1899) therefore deserves attention, particularly as the only published account is brief and ignores relevant data.' Furthermore, the system that was created was unique because of local factors, although, of course, contemporary ideas on education, particularly from England and the Cape were of some influence. Also, this system in its main features has endured down to the present day, and Rhodes’s prophecy therefore proved remarkably accurate. By this ordinance, a disproportionate emphasis was laid upon the development of education for Europeans compared with that for other races, a segregated system of schools for the various races in Southern Rhodesia was established, initiative for the provision of schools for Africans was left exclusively in the hands of Christian missionaries, and the type of education to be given to African children was defined differently from that given in European schools

Calcitonin gene-related peptide-1 (CGRP-1) is a potent regulator of glycogen metabolism in rat skeletal muscle

AbstractWe investigated the effects of CGRP on glucose metabolism in intact rat skeletal muscle preparations that are largely composed of either type I (soleus) or II fibres (e.g. extensor digitorum longus (EDL) or epitrochlearis muscles). CGRP-1 inhibited insulin-stimulated glycogen synthesis in both soleus and EDL muscle preparations. Rat CGRP-1 was a potent stimulator of glycogenolysis only in muscles composed of type II fibres, which depend on high rates of glycogenolysis to produce high power outputs. These results may provide the basis for understanding how CGRP regulate glycogenolysis in type II fibres in vivo

From “where” and “when” to “what” and “why”: archival tags for monitoring “complex” behaviours in fish.

Understanding the movements (“where” and “when”) and behaviour (“what” and, hopefully, “why”) of individuals and populations is key to answering fundamental questions in fish ecology. The use of archival tags in telemetry studies of marine fish have, by and large, involved recording “simple” measurements of variables such as pressure (giving depth), temperature and light over extended timescales. These have then been used to provide information about location and movement of individuals. However, our understanding of more complex behaviours (i.e. what fish are doing as different from spatial movements) has usually been inferred from movement data because it has not been possible to record directly specific behavioural events such as feeding or spawning. This is because the events are usually infrequent, irregular and often quite brief and so not amenable to a technology based on taking regular but infrequent records of continuously available variables. The recent implementation of new sensors (e.g. physical movement, tri-axial accelerometers), rapid (< 30 Hz) sampling capabilities, enhanced memory and more complex data capture protocols has lead to the development of archival tags that can be used to detect and record complex behaviours such as feeding and spawning. We describe recent developments with archival tags and their use to monitor feeding and spawning in fish together with the application of tri-axial accelerometry that can be used to quantify behaviour and metabolic rate. These can then be used to assess the cost of behaviours with a view to understanding how appropriate they are as responses to environmental variability. Keywords: telemetry, behaviour, data storage ta

FRET-Based Detection of M1 Muscarinic Acetylcholine Receptor Activation by Orthosteric and Allosteric Agonists

Muscarinic acetylcholine receptors (mAChRs) are 7-transmembrane, G protein-coupled receptors that regulate a variety of physiological processes and represent potentially important targets for therapeutic intervention. mAChRs can be stimulated by full and partial orthosteric and allosteric agonists, however the relative abilities of such ligands to induce conformational changes in the receptor remain unclear. To gain further insight into the actions of mAChR agonists, we have developed a fluorescently tagged M(1) mAChR that reports ligand-induced conformational changes in real-time by changes in Förster resonance energy transfer (FRET).Variants of CFP and YFP were inserted into the third intracellular loop and at the end of the C-terminus of the mouse M(1) mAChR, respectively. The optimized FRET receptor construct (M(1)-cam5) was expressed stably in HEK293 cells.The variant CFP/YFP-receptor chimera expressed predominantly at the plasma membrane of HEK293 cells and displayed ligand-binding affinities comparable with those of the wild-type receptor. It also retained an ability to interact with Gα(q/11) proteins and to stimulate phosphoinositide turnover, ERK1/2 phosphorylation and undergo agonist-dependent internalization. Addition of the full agonist methacholine caused a reversible decrease in M(1) FRET (F(EYFP)/F(ECFP)) that was prevented by atropine pre-addition and showed concentration-dependent amplitude and kinetics. Partial orthosteric agonists, arecoline and pilocarpine, as well as allosteric agonists, AC-42 and 77-LH-28-1, also caused atropine-sensitive decreases in the FRET signal, which were smaller in amplitude and significantly slower in onset compared to those evoked by methacholine.The M(1) FRET-based receptor chimera reports that allosteric and orthosteric agonists induce similar conformational changes in the third intracellular loop and/or C-terminus, and should prove to be a valuable molecular reagent for pharmacological and structural investigations of M(1) mAChR activation