1,721,012 research outputs found
The weaver mutation reverses the function of dopamine and GABA in mouse dopaminergic neurons
No full textIn the present study, we characterized the intrinsic electrophysiological properties and the membrane currents activated by dopamine (DA) D(2) and GABA(B) receptors in midbrain dopaminergic neurons, maintained in vitro in a slice preparation, from wild-type and homozygous weaver (wv/wv) mice. By using patch-clamp techniques, we found that membrane potential, apparent input resistance, and spontaneous firing of wv/wv dopaminergic neurons were similar to those of dopamine-containing cells recorded from nonaffected (+/+) animals. More interestingly, the wv/wv neurons were excited rather than inhibited by dopamine and the GABA(B) agonist baclofen. This neurotransmitter-mediated excitation was attributable to the activation of a G-protein-gated inward current that reversed polarity at a membrane potential of approximately -30 mV. We suggest that the altered behavior of the receptor-operated wv G-protein-gated inwardly rectifying K(+) channel 2 (GIRK2) might be related to the selective degeneration of the dopaminergic neurons. In addition, the wv GIRK2 would not only suppress the autoreceptor-mediated feedback inhibition of DA release but could also establish a feedforward mechanism of DA release in the terminal fields
Distribution of TRPC1 receptors in dendrites of rat substantia nigra: a confocal and electron microscopy study.
No full textTransient receptor potential channels (TRPC) are plasma membrane, non-selective cationic channels and have been proposed as candidates involved in the regulation of cellular Ca2+ influx. The expression, at mRNA level, of several TRPCs has been demonstrated recently in dopaminergic neurons of the substantia nigra (SN). The aim of the present study was to characterize the expression of TRPC1, at a protein level, in the substantia nigra neurons and non-excitable cells of Wistar rats. Single-label immunohistochemistry and double-label immunofluorescence were used to study the expression of TRPC1 among substantia nigra dopamine neurons and cellular processes using antibodies against tyrosine hydroxylase (TH), substance P (SP), enkephalin, synaptophysin, vesicular glutamate transporter-2 (Vglut-2), microtubule associated protein-2 and metabotropic glutamate receptor 1 (mGluR1). Moreover, the ultrastructural localization of TRPC1 was investigated by means of electron microscopy. A set of dual label experiments was also performed to investigate the presence of TRPC1 among glial cells. Our results showed that TRPC1 is localized mainly in dendritic processes of dopamine neurons, whereas a relatively small percentage of neuronal somata display a light TRPC1 immunoreactivity. Such results were confirmed by our electron microscopy observations. Our study demonstrates, for the first time, a coexpression of TRPC1 and mGluR1 receptors in dendrites of the substantia nigra dopaminergic neurons. Such observation reinforces the concept of an involvement of TRPC1 in mGluR1-mediated excitatory inputs in rat dopamine neurons
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
Immunohistochemical localization of receptor for advanced glycation end (RAGE) products in the R6/2 mouse model of Huntington's disease
No full textThe receptor for advanced glycation end (RAGE) products is a multi-ligand receptor that belongs to the immunoglobulin superfamily of cell surface receptors, whose ligands are known to be upregulated in neuropathological conditions. RAGE upregulation has been described in neurodegenerative diseases, such as Alzheimer's disease, Creutzfeldt–Jakob's disease and Huntington's disease (HD). To analyze in detail the implication of RAGE in HD, we studied the immunohistochemical distribution of RAGE in the striatum of the R6/2 mouse model of HD, with particular attention to the neuronal subpopulations and their relative vulnerability to HD neurodegeneration. We show that RAGE immunoreactivity is evenly distributed to the cytoplasm of neurons in the wild type mouse, while it is finely granular in the cytoplasm of striatal neurons of R6/2 mouse. RAGE is distributed in 98% of spiny projection neurons, both in the normal mouse and in the R6/2. RAGE co-localizes with all of the striatal interneuron subsets both in the wild-type and in the R6/2 mouse. However, the intensity of RAGE immunoreactivity is significantly higher in the spiny neurons and in the PARV neurons of R6/2 mouse, whereas it is comparable between R6/2 and wild-type in the cholinergic and somatostatinergic interneurons. These data support the concept that RAGE is upregulated in the neurodegenerative process of HD, and suggests that its activation is related to the individual vulnerability of the striatal neuronal subtype
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
Nuclear localization of phosphodiesterase 10A (PDE10A) in the R6/2 mouse striatal interneurons
No full textIntroduction: Cyclic nucleotides play an important role as second messengers in the CNS. Intracellular concentrations of cAMP and cGMP are modulated by the rate of degradation by a variety of phosphodiesterases (PDEs). PDE10A is the single member of one of the newest PDE gene families. PDE10A has been observed in the brain mostly in the striatal projec- tion neurons [1]. However, we have previously observed [unpublished data], in the striatum, a number of PDE10 immunoreactive neurons that were not projection neurons. Methods: R6/2 mice and their wild type littermates were sacrificed at 5,
9, 13 weeks of age, and single and double label immunohistochemis- try were performed to identify the different neuronal subtypes of the striatum (medium spiny, choliner- gic, parvalbuminergic, somatos- tatinergic). Results: PDE10A was observed in all subtypes of striatal neurons. In the spiny projection neurons, PDE10A localized in the cytoplasm, whereas in the striatal interneurons, regardless of the sub- type, PDE10A displayed a clearly nuclear localization. This was true both for the wild type and for the R6/2 mice. Conclusions: Our study demonstrates that PDE10A is con- tained not only in the medium spiny neurons, but also in the striatal in- terneurons. Moreover, the different compartmentalization might be ex- plained by a different activity exert- ed by PDE10A between projection neurons and interneurons.
Reference
[1] Seeger TF, Bartlett B, Coskran TM, Culp JS, James LC, Krull DL, Lanfear J, Ryan AM, Schmidt CJ, Strick CA, Var- ghese AH, Williams RD, Wylie PG, Men- niti FS. Immunohistochemical localiza- tion of PDE10A in the rat brain. Brain Res. 2003; 985: 113-126
Immunohistochemical localization of Receptor for advanced glycation end products (RAGE) in the R6/2 mouse model of Huntington’s disease
No full textIntroduction: The receptor for
advanced glycation end-products
(RAGE) is a multi-ligand receptor
that belongs to the immunoglobulin
superfamily of cell surface receptors,
whose ligands are known to be upregulated
in neuropathological conditions.
RAGE up-regulation has been
described in neurodegenerative diseases,
such as Alzheimer’s disease,
Creutzfeldt-Jakob disease and Huntington’s
disease (HD) [1]. Materials
and methods: To analyze in detail the
implication of RAGE in HD, we studied
the immunohistochemical distribution
of RAGE in the striatum of
the R6/2 mouse model of HD, with
particular attention to the neuronal
subpopulations and their relative vulnerability
to HD neurodegeneration.
Results: We show that RAGE immunoreactivity munoreactivity
is evenly distributed
to the cytoplasm of neurons in the
wild type mouse, while it is spot-like
in the R6/2 mouse. Moreover, RAGE
is expressed in the striatum with an
uneven distribution that reminds of the
striosome pattern, but does not overlap
with the calbindin-labeled patch-matrix
compartmentalization. RAGE is distributed
in 90% of spiny projection
neurons, both in the normal mouse
and in the R6/2. RAGE co-localizes
with all of the striatal interneuron subsets
both in the wild-type and in the
R6/2 mouse. However, the intensity
ofRAGEimmunoreactivity is significantly
higher in the spiny neurons and
in the PARV and CALR neurons of
R6/2 mouse, whereas it is comparable
between R6/2 and wild-type in the
cholinergic and somatostatinergic interneurons.
Conclusions: These data
support the concept that RAGE is
upregulated in the neurodegenerative
process of HD, and suggests that its activation is related to the individual
vulnerability of the striatal neuronal subtype.
References
[1] Ma et al. 2004
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
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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