scholarly journals Constitutive deletion of translin (Tsn) enhances locomotor response to amphetamine: role of developmental effects

2020 ◽  
Author(s):  
Xiuping Fu ◽  
Aparna P. Shah ◽  
Jacqueline Keighron ◽  
Ta-Chung M. Mou ◽  
Bruce Ladenheim ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Initial Dose ◽  
Behavioral Plasticity ◽  
Locomotor Response ◽  
Striatal Neurons ◽  
Developmental Effects ◽  
Dependent Form ◽  
Induced Changes ◽  
Amphetamine Sensitization

AbstractThe translin/trax microRNA-degrading enzyme mediates activity-induced changes in translation that underlie several long-lasting forms of cellular plasticity. As translin and trax are expressed in dopaminergic and striatal neurons, we investigated whether deletion of Tsn blocks amphetamine sensitization, a long-lasting, translation-dependent form of behavioral plasticity.Although we had hypothesized that constitutive Tsn deletion would impair amphetamine sensitization, we found, instead, that it enhances the hyperlocomotion produced by the initial dose of amphetamine. Since these mice display elevated adiposity, which alters pharmacokinetics of many drugs, we measured brain levels of amphetamine in Tsn knockout mice and found that these are elevated. As conditional Tsn deletion in adulthood does not impact adiposity, we monitored the locomotor response to amphetamine following this manipulation. Acute and sensitized responses to amphetamine are not altered in these mice, indicating that the enhanced amphetamine response displayed by constitutive Tsn knockout mice is due to Tsn absence during development.

scholarly journals The Role of Dickkopf-1 in Thyroid Hormone–Induced Changes of Bone Remodeling in Male Mice

Endocrinology ◽  
2019 ◽  
Vol 160 (3) ◽  
pp. 664-674 ◽  
Author(s):  
Elena Tsourdi ◽  
Juliane Colditz ◽  
Franziska Lademann ◽  
Eddy Rijntjes ◽  
Josef Köhrle ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Bone Mass ◽  
Bone Turnover ◽  
Knockout Mice ◽  
Bone Volume ◽  
Bone Homeostasis ◽  
Male Mice ◽  
Induced Changes ◽  
Dickkopf 1

Abstract Thyroid hormones regulate bone homeostasis, and exogenously induced hyperthyroidism and hypothyroidism in mice was recently found to be associated with an altered expression of the Wnt inhibitor Dickkopf-1 (Dkk1), a determinant of bone mass. Here, we assessed the role of Dkk1 in thyroid hormone–induced changes in bone using conditional Dkk1 knockout mice. Male mice with a global (Dkk1fl/fl;Rosa26-CreERT2) or osteocyte-specific (Dkk1fl/fl;Dmp1:Cre) deletion of Dkk1 were pharmacologically rendered hypothyroid or hyperthyroid. The bone phenotype was analyzed using micro-CT analysis, dynamic histomorphometry, and serum concentrations of bone turnover markers. Hypothyroid and hyperthyroid Cre-negative mice of either Cre line revealed the expected changes in bone volume with hypothyroid mice displaying a 40% to 60% increase in vertebral trabecular bone volume, while hyperthyroid mice lost 45% to 60% of bone volume. Similar changes were observed at the spine. Interestingly, Cre-positive mice of both lines did not gain or lose as much bone at the femur when rendered hypothyroid or hyperthyroid. While Cre-negative hypothyroid mice gained 80% to 100% bone volume, Cre-positive hypothyroid mice only increased their bone volume by 55% to 90%. Similarly, Cre-negative hyperthyroid mice lost 74% to 79% bone, while Cre-positive hyperthyroid mice merely lost 40% to 54%. Despite these site-specific differences, both global and osteocyte-specific Dkk1 knockout mice displayed similar changes in bone turnover as their Cre-negative controls in the hypothyroid and hyperthyroid states. While osteoblast and osteoclast parameters were increased in hyperthyroidism, hypothyroidism potently suppressed bone cell activities. Loss of Dkk1 is not sufficient to fully reverse thyroid hormone–induced changes in bone mass and bone turnover.

scholarly journals Dopamine D1 receptor-expressing neurons activity is essential for locomotor and sensitizing effects of a single injection of cocaine

2020 ◽  
Author(s):  
Yukari Nakamura ◽  
Sophie Longueville ◽  
Akinori Nishi ◽  
Denis Herve ◽  
Jean-Antoine Girault ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Transgenic Mice ◽  
D1 Receptor ◽  
Designer Drugs ◽  
Locomotor Sensitization ◽  
Locomotor Response ◽  
Striatal Neurons ◽  
Cocaine Administration ◽  
Injection Protocol

D1 dopamine receptors play an important role in the effects of cocaine. Here we investigated the role of neurons which express these receptors (D1-neurons) in the acute locomotor effects of cocaine and the locomotor sensitization observed after a second injection of this drug. We inhibited D1-neurons using double transgenic mice conditionally expressing the inhibitory Gi-coupleddesigner receptor exclusively activated by designer drugs(Gi-DREADD) in D1-neurons. Chemogenetic inhibition of D1-neurons by a low dose of clozapine (0.1 mg/kg) decreased the induction of Fos in striatal neurons. It diminished the basal locomotor activity and acute hyper-locomotion induced by cocaine (20 mg/kg). Clozapine 0.1 mg/kg had no effect by itself and did not alter cocaine effects in non-transgenic mice. Inhibition of D1-neurons during the first cocaine administration reduced the sensitization of the locomotor response in response to a second cocaine administration ten days later. At day 11, inhibition of D1-neurons by clozapine stimulation of Gi-DREADD, prevented the expression of the sensitized locomotor response, whereas at day 12, in the absence of clozapine and D1-neurons inhibition, all mice displayed a sensitized response to cocaine. These results show that chemogenetic inhibition of D1-neurons decreases spontaneous and cocaine-induced locomotor activity. It blunts the induction and prevents the expression of sensitization in a two-injection protocol of sensitization but does not alter established sensitization. Our study further supports the central role of D1-neurons in mediating the acute locomotor effects of cocaine and its sensitization.

Digital x-ray mapping of nanometer-size supported bimetallic catalysts

1988 ◽  
Vol 46 ◽  
pp. 530-531
Author(s):  
L. T. Germinario
Keyword(s):  
Background Radiation ◽  
Metal Cluster ◽  
Single Element ◽  
Beam Diameter ◽  
X Rays ◽  
X Ray ◽  
Major Interest ◽  
Induced Changes

Understanding the role of metal cluster composition in determining catalytic selectivity and activity is of major interest in heterogeneous catalysis. The electron microscope is well established as a powerful tool for ultrastructural and compositional characterization of support and catalyst. Because the spatial resolution of x-ray microanalysis is defined by the smallest beam diameter into which the required number of electrons can be focused, the dedicated STEM with FEG is the instrument of choice. The main sources of errors in energy dispersive x-ray analysis (EDS) are: (1) beam-induced changes in specimen composition, (2) specimen drift, (3) instrumental factors which produce background radiation, and (4) basic statistical limitations which result in the detection of a finite number of x-ray photons. Digital beam techniques have been described for supported single-element metal clusters with spatial resolutions of about 10 nm. However, the detection of spurious characteristic x-rays away from catalyst particles produced images requiring several image processing steps.

Cannabinoid-induced changes in the immune system: The role of microRNAs

2021 ◽  
Vol 98 ◽  
pp. 107832
Author(s):  
Hirva K. Bhatt ◽  
Dana Song ◽  
Gyen Musgrave ◽  
P.S.S. Rao
Keyword(s):  
Immune System ◽  
Induced Changes

scholarly journals Space Radiation-Induced Alterations in the Hippocampal Ubiquitin-Proteome System

2021 ◽  
Vol 22 (14) ◽  
pp. 7713
Author(s):  
Alyssa Tidmore ◽  
Sucharita M. Dutta ◽  
Arriyam S. Fesshaye ◽  
William K. Russell ◽  
Vania D. Duncan ◽  
...  
Keyword(s):  
Spatial Memory ◽  
Memory Performance ◽  
Space Radiation ◽  
Label Free ◽  
Proteomic Profiling ◽  
Neurocognitive Deficits ◽  
Male Wistar Rats ◽  
Radiation Induced ◽  
Induced Changes

Exposure of rodents to <20 cGy Space Radiation (SR) impairs performance in several hippocampus-dependent cognitive tasks, including spatial memory. However, there is considerable inter-individual susceptibility to develop SR-induced spatial memory impairment. In this study, a robust label-free mass spectrometry (MS)-based unbiased proteomic profiling approach was used to characterize the composition of the hippocampal proteome in adult male Wistar rats exposed to 15 cGy of 1 GeV/n 48Ti and their sham counterparts. Unique protein signatures were identified in the hippocampal proteome of: (1) sham rats, (2) Ti-exposed rats, (3) Ti-exposed rats that had sham-like spatial memory performance, and (4) Ti-exposed rats that impaired spatial memory performance. Approximately 14% (159) of the proteins detected in hippocampal proteome of sham rats were not detected in the Ti-exposed rats. We explored the possibility that the loss of the Sham-only proteins may arise as a result of SR-induced changes in protein homeostasis. SR-exposure was associated with a switch towards increased pro-ubiquitination proteins from that seen in Sham. These data suggest that the role of the ubiquitin-proteome system as a determinant of SR-induced neurocognitive deficits needs to be more thoroughly investigated.

scholarly journals The Effect of Dual Language Activation on L2-Induced Changes in L1 Speech within a Code-Switched Paradigm

Languages ◽  
2021 ◽  
Vol 6 (3) ◽  
pp. 114
Author(s):  
Ulrich Reubold ◽  
Sanne Ditewig ◽  
Robert Mayr ◽  
Ineke Mennen
Keyword(s):  
Dual Language ◽  
Native Speakers ◽  
Predictor Variable ◽  
Predictor Variables ◽  
Acoustic Measures ◽  
Before And After ◽  
Language Activation ◽  
Dual Activation ◽  
Induced Changes

The present study sought to examine the effect of dual language activation on L1 speech in late English–Austrian German sequential bilinguals, and to identify relevant predictor variables. To this end, we compared the English speech patterns of adult migrants to Austria in a code-switched and monolingual condition alongside those of monolingual native speakers in England in a monolingual condition. In the code-switched materials, German words containing target segments known to trigger cross-linguistic interaction in the two languages (i.e., [v–w], [ʃt(ʁ)-st(ɹ)] and [l-ɫ]) were inserted into an English frame; monolingual materials comprised English words with the same segments. To examine whether the position of the German item affects L1 speech, the segments occurred either before the switch (“He wants a Wienerschnitzel”) or after (“I like Würstel with mustard”). Critical acoustic measures of these segments revealed no differences between the groups in the monolingual condition, but significant L2-induced shifts in the bilinguals’ L1 speech production in the code-switched condition for some sounds. These were found to occur both before and after a code-switch, and exhibited a fair amount of individual variation. Only the amount of L2 use was found to be a significant predictor variable for shift size in code-switched compared with monolingual utterances, and only for [w]. These results have important implications for the role of dual activation in the speech of late sequential bilinguals.

Nitric oxide decreases lung liquid production via guanosine 3′,5′-cyclic monophosphate

2001 ◽  
Vol 280 (5) ◽  
pp. L923-L929 ◽  
Author(s):  
James J. Cummings ◽  
Huamei Wang
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Epithelium ◽  
Fetal Sheep ◽  
Cgmp Analog ◽  
Pulmonary Arterial ◽  
Series Of Experiments ◽  
Lung Liquid ◽  
Tracer Dilution ◽  
Induced Changes

We studied the role of cGMP in nitric oxide (NO)-induced changes in lung liquid production ( J v ) in chronically instrumented fetal sheep. Forty-five studies were done in which J v was measured by a tracer dilution technique. Left pulmonary arterial flow (Qlpa) was measured by a Doppler flow probe. There were two series of experiments. In the first, we gave 8-bromo-cGMP, a cGMP analog, by either the pulmonary vascular or intraluminal route; in the second, we used agents to inhibit or enhance endogenous cGMP activity. When infused directly into the pulmonary circulation, 8-bromo-cGMP significantly increased Qlpa but had no effect on J v. Conversely, when instilled into the lung liquid, 8-bromo-cGMP had no effect on Qlpa but significantly reduced J v. Inhibition of guanylate cyclase activity with methylene blue totally blocked, whereas phosphodiesterase inhibition with Zaprinast significantly enhanced, the effect of instilled NO on J v. Thus the reduction in lung liquid caused by NO appears to be mediated by cGMP, perhaps through a direct effect on the pulmonary epithelium.

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