scholarly journals The distribution of neuronal primary cilia immunoreactive to melanin-concentrating hormone receptor 1 (MCHR1) in the murine prosencephalon

2019 ◽  
Author(s):  
Giovanne B. Diniz ◽  
Daniella S. Battagello ◽  
Bianca S. M. Bono ◽  
Jozélia G. P. Ferreira ◽  
Marianne O. Klein ◽  
...  

AbstractMelanin-concentrating hormone (MCH) is a ubiquitous vertebrate neuropeptide predominantly synthesized by neurons of the diencephalon that can act through two G protein-coupled receptors, called MCHR1 and MCHR2. The expression of Mchr1 has been investigated in both rats and mice, but its synthesis remains poorly described. After identifying an antibody that detects MCHR1 with high specificity, we employed immunohistochemistry to map the distribution of MCHR1 in the CNS of rats and mice. Multiple neurochemical markers were also employed to characterize some of the neuronal populations that synthesize MCHR1. Our results show that MCHR1 is abundantly found in a sensory subcellular structure called the neuronal primary cilium, which has been associated with the detection of free neurochemical agents released to act through volume transmission. Ciliary MCHR1 was found in a wide range of areas, including the olfactory bulb, cortical mantle, striatum, hippocampal formation, amygdala, midline thalamic nuclei, periventricular hypothalamic nuclei, and midbrain areas. No differences were observed between male and female mice, and rats and mice diverged in two key areas: the caudate-putamen nucleus and the subgranular zone of the dentate gyrus. Ciliary MCHR1 was found in close association to several neurochemical markers, including tyrosine hydroxylase, calretinin, kisspeptin, estrogen receptor, oxytocin, vasopressin, and corticotropin-releasing factor. Given the role of neuronal primary cilia in sensing free neurochemical messengers in the extracellular fluid, the widespread distribution of ciliary MCHR1, and the diverse neurochemical populations who synthesize MCHR1, our data indicates that volume transmission may play a prominent role in the normal function of the MCH system.

2000 ◽  
Vol 17 (2) ◽  
pp. 187-196 ◽  
Author(s):  
JOKUBAS ZIBURKUS ◽  
MARTHA E. BICKFORD ◽  
WILLIAM GUIDO

In normal adult cats, a monoclonal antibody directed toward the NR-1 subunit of the N-methyl-d-aspartate (NMDA) receptor (Pharmingen, clone 54.1) produced dense cellular and neuropil labeling throughout all layers of the lateral geniculate nucleus (LGN) and adjacent thalamic nuclei, including the thalamic reticular, perigeniculate, medial intralaminar, and ventral lateral geniculate nuclei. Cellular staining revealed well-defined somata, and in some cases proximal dendrites. NMDAR-1 cell labeling was also evident in the LGN of early postnatal kittens, suggesting that developing LGN cells possess this receptor subunit at or before eye opening. Within the A-layers of the adult LGN, staining encompassed a wide range of soma sizes. Soma size comparisons of NMDAR-1 stained cells with those stained with an antibody directed toward a nonphosphorylated neurofilament protein (SMI-32), which selectively stains Y-relay cells (Bickford et al., 1998), or an antibody to glutamic acid decarboxylase (GAD), which stains for GABAergic interneurons, suggested that NMDA receptors are utilized by relay cells and interneurons. NMDAR-1 staining was also observed in the LGN of cats with early monocular lid suture. Although labeling was apparent in both deprived and nondeprived A-layers of LGN, the distribution of soma sizes was significantly different. In the deprived A-layers of LGN, staining was limited to small- and medium-sized cells. Cells with relatively large soma were lacking. However, cell density measurements as well as soma size comparisons with cells stained for Nissl substance suggested these differences were due to deprivation-induced cell shrinkage and not to a loss of NMDAR-1 staining in Y-cells. Taken together, these results suggest that NMDA receptors are utilized by both relay cells and interneurons in LGN and that alterations in early visual experience do not necessarily affect the expression of NMDA receptors in the LGN.


2017 ◽  
Vol 1 ◽  
pp. 239821281772344 ◽  
Author(s):  
Emma J. Bubb ◽  
Lisa Kinnavane ◽  
John P. Aggleton

This review brings together current knowledge from tract tracing studies to update and reconsider those limbic connections initially highlighted by Papez for their presumed role in emotion. These connections link hippocampal and parahippocampal regions with the mammillary bodies, the anterior thalamic nuclei, and the cingulate gyrus, all structures now strongly implicated in memory functions. An additional goal of this review is to describe the routes taken by the various connections within this network. The original descriptions of these limbic connections saw their interconnecting pathways forming a serial circuit that began and finished in the hippocampal formation. It is now clear that with the exception of the mammillary bodies, these various sites are multiply interconnected with each other, including many reciprocal connections. In addition, these same connections are topographically organised, creating further subsystems. This complex pattern of connectivity helps explain the difficulty of interpreting the functional outcome of damage to any individual site within the network. For these same reasons, Papez’s initial concept of a loop beginning and ending in the hippocampal formation needs to be seen as a much more complex system of hippocampal–diencephalic–cingulate connections. The functions of these multiple interactions might be better viewed as principally providing efferent information from the posterior medial temporal lobe. Both a subcortical diencephalic route (via the fornix) and a cortical cingulate route (via retrosplenial cortex) can be distinguished. These routes provide indirect pathways for hippocampal interactions with prefrontal cortex, with the preponderance of both sets of connections arising from the more posterior hippocampal regions. These multi-stage connections complement the direct hippocampal projections to prefrontal cortex, which principally arise from the anterior hippocampus, thereby creating longitudinal functional differences along the anterior–posterior plane of the hippocampus.


2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Angel L. Pey ◽  
Clare F. Megarity ◽  
David J. Timson

AbstractNAD(P)H quinone oxidoreductase 1 (NQO1) catalyses the two electron reduction of quinones and a wide range of other organic compounds. Its physiological role is believed to be partly the reduction of free radical load in cells and the detoxification of xenobiotics. It also has non-enzymatic functions stabilising a number of cellular regulators including p53. Functionally, NQO1 is a homodimer with two active sites formed from residues from both polypeptide chains. Catalysis proceeds via a substituted enzyme mechanism involving a tightly bound FAD cofactor. Dicoumarol and some structurally related compounds act as competitive inhibitors of NQO1. There is some evidence for negative cooperativity in quinine oxidoreductases which is most likely to be mediated at least in part by alterations to the mobility of the protein. Human NQO1 is implicated in cancer. It is often over-expressed in cancer cells and as such is considered as a possible drug target. Interestingly, a common polymorphic form of human NQO1, p.P187S, is associated with an increased risk of several forms of cancer. This variant has much lower activity than the wild-type, primarily due to its substantially reduced affinity for FAD which results from lower stability. This lower stability results from inappropriate mobility of key parts of the protein. Thus, NQO1 relies on correct mobility for normal function, but inappropriate mobility results in dysfunction and may cause disease.


1992 ◽  
Vol 124 (2) ◽  
pp. 347-358 ◽  
Author(s):  
Roy F. Shepherd

AbstractIndividual larvae of western spruce budworm (Choristoneura occidentalis Freeman) were observed from overwintering emergence to pupation at six locations spread over a wide range of altitudes and thus climate. A weekly census of 100 lower-crown buds per plot indicated large differences in rates of bud development and larval survival among locations.Emerging second-instar larvae attempted to mine swelling buds of Douglas-fir. If the buds were hard and tight, larvae mined 1-year-old needles until penetrable buds were available. Larvae dispersed over the crowns with only one larva becoming established in each bud; thus, many early-emerging and surplus larvae could not find suitable feeding sites and disappeared. Within the protective bud, survival was high. After buds flushed and larvae became exposed, densities dropped, probably due to increased predation and decreased food quality. Correlations indicated a close association between larval survival for the exposed period between bud flush and pupation, and overall larval survival.Douglas-fir trees responded to initial bud removal, but not to needle removal, by inducing latent buds in the axils of needles to grow into active vegetative buds ready to develop and flush the next spring. The number of these new vegetative buds formed was greatest when the initial buds were removed early in the season before flush, and decreased thereafter. Trees with vigorous crowns had the greatest response to defoliation by inducing the largest number of latent buds into becoming active vegetative buds; these were found mainly on the 2- and 3-year-old internodes.


Hippocampus ◽  
2015 ◽  
Vol 25 (9) ◽  
pp. 977-992 ◽  
Author(s):  
Christopher M. Dillingham ◽  
Jonathan T. Erichsen ◽  
Shane M. O'Mara ◽  
John P. Aggleton ◽  
Seralynne D. Vann

2020 ◽  
Vol 4 ◽  
pp. 239821282095716
Author(s):  
Emma J. Bubb ◽  
Andrew J. D. Nelson ◽  
Thomas C. Cozens ◽  
John P. Aggleton

Despite considerable interest in the properties of the cingulum bundle, descriptions of the composition of this major pathway in the rodent brain have not kept pace with advances in tract tracing. Using complementary approaches in rats and mice, this study examined the dense, reciprocal connections the anterior thalamic nuclei have with the cingulate and retrosplenial cortices, connections thought to be major contributors to the rodent cingulum bundle. The rat data came from a mixture of fluorescent and viral tracers, some injected directly into the bundle. The mouse data were collated from the Allen Mouse Brain Atlas. The projections from the three major anterior thalamic nuclei occupied much of the external medullary stratum of the cingulum bundle, where they were concentrated in its more medial portions. These anterior thalamic projections formed a rostral-reaching basket of efferents prior to joining the cingulum bundle, with anteromedial efferents taking the most rostral routes, often reaching the genu of the corpus callosum, while anterodorsal efferents took the least rostral route. In contrast, the return cortico-anterior thalamic projections frequently crossed directly through the bundle or briefly joined the internal stratum of the cingulum bundle, often entering the internal capsule before reaching the anterior thalamus. These analyses confirm that anterior thalamic connections comprise an important component of the rodent cingulum bundle, while also demonstrating the very different routes used by thalamo-cortical and cortico-thalamic projections. This information reveals how the composition of the cingulum bundle alters along its length.


2004 ◽  
pp. S17-S22 ◽  
Author(s):  
PJ Jenkins ◽  
SA Bustin

Cancer risk is determined by a combination of environmental factors and genetic predisposition. Recent evidence suggests that dietary and related factors such as physical activity and body size may influence cancer risk through their effects on the serum concentration of IGF-I and its binding proteins. The growth hormone (GH)/IGF-I axis is involved in both human development as well as the maintenance of normal function and homeostasis in most cells of the body. In addition to their classical role as endocrine hormones, its members regulate a wide range of biological functions such as cell proliferation, differentiation and apoptosis through paracrine and autocrine mechanisms. During cancer development this complex network regulating tissue homeostasis breaks down, with inappropriate expression of the GH/IGF-I axis making an important contribution. The increased understanding of the molecular mechanisms and signalling pathways regulated by the GH/IGF-I axis has started to provide significant insights into the aetiology, prevention and therapy for a number of common cancers.


1974 ◽  
Vol 22 (3) ◽  
pp. 319 ◽  
Author(s):  
HG Cogger

A field study of the thermal relationships of the small agamid lizard A. fordi has been carried out in two areas of mallee in central western New South Wales, where this lizard occurs only in close association with the grass Triodia scariosa. The body temperatures characteristic of various phases in this lizard's die1 cycle have been determined. The behavioural techniques employed to regulate temperature are described; they are similar to those used by a wide range of diurnal heliothermic lizards in other regions. The total effect of these thermoregulatory responses is to maintain an internal thermal environ- ment approaching homoiothermy while the lizard is active. For A. fordi the eccritic body temperature determined from animals in the field is 36.9+-0.16C. Lowering of activity thermal levels occurs in winter, and can be induced at any time by even mild starvation.


Author(s):  
Christopher Potts ◽  
Florian Schwarz
Keyword(s):  

Lakoff (1974) argues that affective demonstratives in English are markers of solidarity, with exclamative overtones deriving from their close association with evaluative predication. Focusing on this, we seek to inform these claims using quantitative corpus evidence. Our experiments suggest that affectivity is not limited to specific uses of this, but rather that it arises in a wide range of linguistic and discourse contexts. We also briefly extend our methodology to demonstrative that and to German diese- (‘this’).


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