Autaptic hippocampal neurons are an architecturally simple model of neurotransmission that express several forms of cannabinoid signaling. Over the past twenty years this model has proven valuable for studies ranging from enzymatic control of endocannabinoid production and breakdown, to CB1 receptor structure/function, to CB2 signaling, understanding 'spice' (synthetic cannabinoid) pharmacology, and more. However, while studying cannabinoid signaling in these neurons, we have occasionally encountered what one might call 'interesting negatives', valid and informative findings in the context of our experimental design that, given the nature of scientific publishing, may not otherwise find their way into the scientific literature. In autaptic hippocampal neurons we have found that: (1) The fatty acid binding protein (FABP) blocker SBFI-26 does not alter CB1-mediated neuroplasticity. (2) 1-AG signals poorly relative to 2-AG in autaptic neurons. (3) Indomethacin is not a CB1 PAM in autaptic neurons. (4) The CB1-associated protein SGIP1a is not necessary for CB1 desensitization. We are presenting these negative or perplexing findings in the hope that they will prove beneficial to other laboratories and elicit fruitful discussions regarding their relevance and significance.
- MeSH
- Endocannabinoids MeSH
- Hippocampus MeSH
- Cannabinoids * pharmacology MeSH
- Synaptic Transmission MeSH
- Neurons MeSH
- Publication type
- Journal Article MeSH
BACKGROUND AND PURPOSE: Src homology 3-domain growth factor receptor-bound 2-like endophilin interacting protein 1 (SGIP1) interacts with cannabinoid CB1 receptors. SGIP1 is abundantly and principally expressed within the nervous system. SGIP1 and CB1 receptors co-localize in axons and presynaptic boutons. SGIP1 interferes with the internalization of activated CB1 receptors in transfected heterologous cells. Consequently, the transient association of CB1 receptors with β-arrestin2 is enhanced and prolonged, and CB1 receptor-mediated ERK1/2 signalling is decreased. Because of these actions, SGIP1 may modulate affect, anxiety, pain processing, and other physiological processes controlled by the endocannabinoid system (ECS). EXPERIMENTAL APPROACH: Using a battery of behavioural tests, we investigated the consequences of SGIP1 deletion in tasks regulated by the ECS in SGIP1 constitutive knockout (SGIP1-/- ) mice. KEY RESULTS: In SGIP1-/- mice, sensorimotor gating, exploratory levels, and working memory are unaltered. SGIP1-/- mice have decreased anxiety-like behaviours. Fear extinction to tone is facilitated in SGIP1-/- females. Several cannabinoid tetrad behaviours are altered in the absence of SGIP1. SGIP1-/- males exhibit abnormal behaviours on Δ9 -tetrahydrocannabinol withdrawal. SGIP1 deletion also reduces acute nociception, and SGIP1-/- mice are more sensitive to analgesics. CONCLUSION AND IMPLICATIONS: SGIP1 was detected as a novel protein associated with CB1 receptors, and profoundly modified CB1 receptor signalling. Genetic deletion of SGIP1 particularly affected behavioural tests of mood-related assessment and the cannabinoid tetrad. SGIP1-/- mice exhibit decreased nociception and augmented responses to CB1 receptor agonists and morphine. These in vivo findings suggest that SGIP1 is a novel modulator of CB1 receptor-mediated behaviour.
- MeSH
- Adaptor Proteins, Signal Transducing physiology MeSH
- Affect MeSH
- Emotions MeSH
- Extinction, Psychological MeSH
- Cannabinoids MeSH
- Mice, Knockout MeSH
- Mice MeSH
- Nociception * MeSH
- Receptor, Cannabinoid, CB1 * genetics MeSH
- Receptors, Cannabinoid MeSH
- Fear MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
Magnetron sputtering was employed for the deposition of cobalt oxide thin films on stainless steel meshes. Catalysts prepared by sputtering in inert and oxidation atmosphere were compared with those obtained by electrochemical deposition and hydrothermal synthesis. Systematic characterization using X-ray diffraction, scanning electron microscopy, N2 physisorption, infrared spectroscopy, Raman spectroscopy, and temperature-programmed reduction by hydrogen allowed detailed monitoring of their physicochemical properties. Ethanol gas-phase oxidation was employed as a model reaction to reveal the catalytic performance of the catalysts. It was shown that the catalyst prepared by magnetron sputtering in oxidation atmosphere exhibited the best mechanical stability among all studied catalysts. Moreover, its catalytic activity was 18 times higher than that of pelletized commercial cobalt oxide.
- MeSH
- Catalysis MeSH
- Cobalt * MeSH
- Oxides * MeSH
- Volatile Organic Compounds * MeSH
- Publication type
- Journal Article MeSH
Antropos ; svazek 9
179 stran : ilustrace, tabulky ; 22 cm
Publikace kolektivu autorů se zaměřuje na tělesné modifikace, na diskusi o hranicích lidského těla a rozdíly mezi lidskými bytostmi a stroji. Volně navazuje na titul Tělo: čichat, česat, hmatat, propichovat, řezat (2014). Kniha Tělo 2.0 staví na teoriích těla a tělesnosti, které se od začátku 20. století rozvíjejí ve vědách o člověku, společnosti a kultuře. Jednotlivé kapitoly se věnují poruchám příjmu potravy, skalpování, rozdílům mezi člověkem a stroji, funkčním modifikacím těla a provádění extrémních modifikací. Kapitoly sjednocuje téma bolesti a překračování hranic lidského těla. Předmětem knihy je antropologické a etnologické zkoumání lidského těla a tělesnosti.
- Conspectus
- Fyzická antropologie
- NML Fields
- antropologie
- NML Publication type
- kolektivní monografie
Many diseases of the nervous system are accompanied by alterations in synaptic functions. Synaptic plasticity mediated by the endogenous cannabinoid system involves the activation of the cannabinoid receptor 1 (CB1R). The principles of CB1R signaling must be understood in detail for its therapeutic exploration. We detected the Src homology 3-domain growth factor receptor-bound 2-like (endophilin) interacting protein 1 (SGIP1) as a novel CB1R partner. SGIP1 is functionally linked to clathrin-mediated endocytosis and its overexpression in animals leads to an energy regulation imbalance resulting in obesity. We report that SGIP1 prevents the endocytosis of activated CB1R and that it alters signaling via the CB1R in a biased manner. CB1R mediated G-protein activation is selectively influenced by SGIP1, β-arrestin associated signaling is changed profoundly, most likely as a consequence of the prevention of the receptor's internalization elicited by SGIP1.
- MeSH
- beta-Arrestin 2 metabolism MeSH
- Cell Membrane drug effects metabolism MeSH
- Endocytosis drug effects physiology MeSH
- HEK293 Cells MeSH
- Humans MeSH
- MAP Kinase Signaling System physiology MeSH
- Brain metabolism MeSH
- Mice MeSH
- Neurons metabolism MeSH
- Rats, Wistar MeSH
- Receptor, Cannabinoid, CB1 metabolism MeSH
- Saccharomyces cerevisiae MeSH
- Two-Hybrid System Techniques MeSH
- Transfection MeSH
- Carrier Proteins genetics metabolism MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
The assembly of two covalently linked monomers into dimeric complexes is a prerequisite for metabotropic glutamate receptor 1 (mGluR1) function. The former concept of a strictly homodimeric subunit contribution in metabotropic glutamate receptor complexes has recently been brought into question. Alternative splicing of the GRM1 gene results in expression of variants that vary within their intracellular C-termini. Here we bring evidence that the short mGluR1b variant is found preferentially in a complex with the long mGluR1a variant in the rodent brain. The mGluR1a and mGluR1b variants distribution overlaps in Purkinje cells and the two variants colocalize in their spines. However mGluR1a and mGluR1b show distinct sub-cellular localization when expressed alone in neurons. We discovered that trafficking of mGluR1b to distal dendrites is reliant on its association with mGluR1a and that the long C-terminus of mGluR1a within the mGluR1a/b dimer is necessary for trafficking of the complex.
- MeSH
- Biological Transport, Active MeSH
- Dendritic Spines metabolism MeSH
- Dimerization MeSH
- Electrophoresis, Polyacrylamide Gel MeSH
- Microscopy, Electron MeSH
- HEK293 Cells MeSH
- Immunoblotting MeSH
- Immunohistochemistry MeSH
- Rats MeSH
- Cells, Cultured MeSH
- Humans MeSH
- Brain metabolism MeSH
- Neurons metabolism MeSH
- Rats, Sprague-Dawley MeSH
- Rats, Wistar MeSH
- Protein Isoforms MeSH
- Receptors, Metabotropic Glutamate metabolism MeSH
- Subcellular Fractions metabolism MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Intramural MeSH
Antropos
248 stran : ilustrace, portréty, faksimilie ; 22 cm
- MeSH
- Anthropology, Physical MeSH
- Esthetics MeSH
- Physical Appearance, Body MeSH
- Anthropology, Cultural MeSH
- Human Body MeSH
- Interdisciplinary Studies MeSH
- Self Care MeSH
- Conspectus
- Antropologie
- NML Fields
- antropologie
- NML Publication type
- kolektivní monografie
- MeSH
- Unconsciousness nursing MeSH
- Adult MeSH
- Physical Stimulation * MeSH
- Middle Aged MeSH
- Humans MeSH
- Critical Care Nursing * MeSH
- Inpatients MeSH
- Rehabilitation MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
New cholic acid based calix[4]pyrroles and porphyrins were prepared and their properties were studied. It was confirmed by spectral measurements that the superassembly of 5,15-bis(3α,7α,12α-trihydroxy-5β-cholan-24-yl)-10,20-diphenylporphyrin, the best candidate for this study from the conjugates prepared, may be influenced not only by the solvent mixture composition (polar/non-polar component ratio) but by time as well.
