1,723,125 research outputs found
Special issue “The multifaceted activities of nervous and non-nervous neuronal nicotinic acetylcholine receptors in physiology and pathology”
Full text linkDiversity of native nicotinic receptor subtypes in mammalian brain
Full text linkNeuronal nicotinic acetylcholine receptors (nAChRs) are a heterogeneous family of pentameric ligand-gated cation channels that are expressed throughout the brain and involved in a wide range of physiological and pathophysiological processes. The nAChR subtypes share a common basic structure, but their biophysical and pharmacological properties depend on their subunit composition, which is therefore central to understanding their function in the nervous system and discovering new subtype selective drugs. The development of new technologies and the generation of mice carrying deletions or the expression of gain-of-function nAChR subunits, or GFP-tagged receptor genes has allowed the in vivo identification of complex subtypes and to study the role of individual subtypes in specific cells and complex neurobiological systems but much less is known about which native nAChR subtypes are involved in specific physiological functions and pathophysiological conditions in human brain. We briefly review some recent findings concerning the structure and function of native nAChRs, focussing on the subtypes identified in the rodent habenulo-interpeduncular pathway, a pathway involved in nicotine reinforcement and withdrawal. We also discuss recent findings concerning the expression of native subtypes in primate brain. This article is part of the Special Issue entitled ‘The Nicotinic Acetylcholine Receptor: From Molecular Biology to Cognition’
alpha 7 but not alpha 4 AChR subunit expression is regulated by light in developing primary visual cortex
No full textIn the present paper we analyzed the expression pattern of the alpha4 and alpha7 nicotinic acetylcholine receptor (nAChR) subunits in the rat visual cortex through postnatal development, to clarify whether their expression is developmentally regulated and whether eventual developmental changes are regulated by visual experience. We found that both alpha4 and alpha7 mRNA levels accumulate from postnatal day 12 (P12) before eye opening, to around P35. The immunohistochemical results indicated that both subunits are expressed throughout all cortical laminae, except layer I. alpha4 subunit immunohistochemistry revealed significant increments in the number of positive cells in layers V and VI after eye opening. In the case of the alpha7 subunit, the number of immunoreactive cells increased in all cortical layers soon after eye opening, except in layer VI, matching the results found at the transcriptional level. In animals reared in darkness from P9 to P22, the relative amount of the alpha4 mRNA and the number of immunoreactive cells exhibited no changes. H-3-epibatidine binding experiments showed that the number of heteromeric nAChR subunitsin dark-reared rats did not change with respect to age-matched controls, thus confirming the immunohistochemical results. The mRNA of the alpha7 subunit remained stable in dark-reared rats, whereas the number and distribution of immunoreactive cells changed. Moreover, the number of I-125 alphabungarotoxin-binding nAChRs was significantly increased in dark-reared animals. These results indicate that visual cortex stimulation by visual input is an essential step for alpha7 nAChR normal expression, suggesting a possible role for these receptors in an experience-dependent fashion on the maturation of this cortical area. (C) 2004 Wiley-Liss, Inc
Auxiliary protein and chaperone regulation of neuronal nicotinic receptor subtype expression and function
Full text linkNeuronal nicotinic acetylcholine receptors (nAChRs) are a family of pentameric, ligand-gated ion channels that are located on the surface of neurons and non-neuronal cells and have multiple physiological and pathophysiological functions. In order to reach the cell surface, many nAChR subtypes require the help of chaperone and/or auxiliary/accessory proteins for their assembly, trafficking, pharmacological modulation, and normal functioning in vivo. The use of powerful genome-wide cDNA screening has led to the identification and characterisation of the molecules and mechanisms that participate in the assembly and trafficking of receptor subtypes, including chaperone and auxiliary or accessory proteins. The aim of this review is to describe the latest findings concerning nAChR chaperones and auxiliary proteins and pharmacological chaperones, and how some of them control receptor biogenesis or regulate channel activation and pharmacology. Some auxiliary proteins are subtype selective, some regulate various subtypes, and some not only modulate nAChRs but also target other receptors and signalling pathways. We also discuss how changes in auxiliary proteins may be involved in nAChR dysfunctions
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
α9-Containing Nicotinic Receptors in Cancer
Full text linkNeuronal nicotinic acetylcholine receptors containing the α9 or the α9 and α10 subunits are expressed in various extra-neuronal tissues. Moreover, most cancer cells and tissues highly express α9-containing receptors, and a number of studies have shown that they are powerful regulators of responses that stimulate cancer processes such as proliferation, inhibition of apoptosis, and metastasis. It has also emerged that their modulation is a promising target for drug development. The aim of this review is to summarize recent data showing the involvement of these receptors in controlling the downstream signaling cascades involved in the promotion of cancer
Visual Acuity Is Reduced in Alpha 7 Nicotinic Receptor Knockout Mice
No full textPURPOSE. Nicotinic receptors (nAChRs) are part of a heterogeneous family of pentameric ligand-gated ion channels that are widely expressed in the visual system. The impact of alpha 7 homomeric nAChRs on visual function was investigated using mutant mice lacking the alpha 7 nicotinic receptor subunit. METHODS. The spatial resolution limit was measured in alpha 7 knockout (alpha 7 KO) and age-matched control mice using three independent methods: an operant behavioral visual task (Prusky maze), cortical visual evoked potentials (VEPs), and the pattern electroretinogram (PERG) evoked by alternating gratings of different spatial frequencies and contrasts. RESULTS. Visual acuity measured by means of the visual water maze task was significantly decreased in the alpha 7 KO mice and, concordantly, there was a reduction of the cortical spatial resolution limit measured by VEPs. However, the PERG was normal in alpha 7 KO mice, compared with control mice. The use of fluorescently tagged cholera toxin showed that projections from the retina segregate normally in alpha 7 KO mice and, in line with this, the visual cortical responses elicited by stimulating either eye were normally balanced in both visual cortices and showed no retinotopic anomalies. CONCLUSIONS. These findings indicate that the absence of the alpha 7 nicotinic subunit reduces visual acuity. Because the cortical output has an abnormal spatial resolution but retinal output is preserved, it can be concluded that the low visual acuity was due to a deficit specifically present in the visual cortex. (Invest Ophthalmol Vis Sci. 2012;53:1211-1218) DOI:10.1167/iovs.11-800
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