Read by QxMD icon Read

ACS Chemical Neuroscience

Santosh R Alluri, Patrick J Riss
We report the synthesis, radiosynthesis, and characterization of a radioligand for poly(ADP-ribose) polymerase (PARP). PARP is of central importance in cell homeostasis, neuroplasticity, and neurodegeneration in the brain. A radiolabeled PARP inhibitor was developed and used for autoradiographic quantification of PARP protein concentration in wild-type and transgenic rodent brains ex vivo in high resolution. The binding of [3 H]rucaparib was found to be confined to PARP-expressing domains, for example, cerebellar cortex or hippocampal regions in both models...
March 16, 2018: ACS Chemical Neuroscience
Lisa K Gouwens, Mudar S Ismail, Victoria A Rogers, Nathan T Zeller, Evan C Garrad, Fatima S Amtashar, Nyasha J Makoni, David C Osborn, Michael R Nichols
Microvesicles (MVs) and exosomes comprise a class of cell-secreted particles termed extracellular vesicles (EVs). These cargo-holding vesicles mediate cell-to-cell communication and have recently been implicated in neurodegenerative diseases such as Alzheimer's disease (AD). The two types of EVs are distinguished by the mechanism of cell release and their size, with the smaller exosomes and the larger MVs ranging from 30 to 100 nm and 100 nm to 1 μm in diameter, respectively. MV numbers are increased in AD and appear to interact with amyloid-β peptide (Aβ), the primary protein component of the neuritic plaques in the AD brain...
March 15, 2018: ACS Chemical Neuroscience
Guo Zhang, Wang-Ding Yuan, Ferdinand S Vilim, Elena V Romanova, Ke Yu, Si-Yuan Yin, Zi-Wei Le, Ying-Yu Xue, Ting-Ting Chen, Guo-Kai Chen, Song-An Chen, Elizabeth C Cropper, Jonathan V Sweedler, Klaudiusz R Weiss, Jian Jing
When individual neurons in a circuit contain multiple neuropeptides, these peptides can target different sets of follower neurons. This endows the circuit with a certain degree of flexibility. Here we identified a novel family of peptides, the Aplysia SPTR-Gene Family-Derived peptides (apSPTR-GF-DPs). We demonstrated apSPTR-GF-DPs, particularly apSPTR-GF-DP2, are expressed in the Aplysia CNS using immunohistochemistry and MALDI-TOF MS. apSPTR-GF-DP2 is present in single projection neurons, e.g., in the cerebral-buccal interneuron-12 (CBI-12)...
March 15, 2018: ACS Chemical Neuroscience
Ewa Siucinska, Wojciech Brutkowski, Tytus Bernas
We found previously that fear conditioning by combined stimulation of a row B facial vibrissae (conditioned stimulus, CS) with a tail shock (unconditioned stimulus, UCS) leads to expansion of the cortical representation of the "trained" row, labeled with 2-deoxyglucose (2DG), in the layer IIIb/IV of the adult mouse the primary somatosensory cortex (S1) 24 h later. We have observed that learning - dependent these plastic changes are manifested by increased expression of somatostatin, cholecystokinin (SST+, CCK+) but not parvalbumin (PV+) immunopositive interneurons...
March 14, 2018: ACS Chemical Neuroscience
Angela M Getz, Pierre Wijdenes, Saba Riaz, Naweed I Syed
All functions of the nervous system are contingent upon the precise organization of neuronal connections that are initially patterned during development, and then continually modified throughout life. Determining the mechanisms that specify the formation and functional modulation of synaptic circuitry are critical to advancing both our fundamental understanding of the nervous system as well as the various neurodevelopmental, neurological, neuropsychiatric, and neurodegenerative disorders that are met in clinical practice when these processes go awry...
March 12, 2018: ACS Chemical Neuroscience
Karen P Maruska, Russell D Fernald
Most biomedical research is performed using a very limited number of "model" species. In part, this has resulted from a combination of full genomes, manipulation of genes, and short generation times in these species. However, the advent of low cost sequencing and gene editing in any organism has increased the use of non-traditional organisms. Many scientists have paraphrased the adage by Krogh that for many biological problems some species will prove to be most convenient and useful to study (1). In particular, using organisms most suited to the specific research question can lead to novel insights about fundamental physiological, neurobiological, immunological and neuroendocrine systems that can advance our understanding of the well-being and health of humans...
March 9, 2018: ACS Chemical Neuroscience
Tingting Fu, Guoxun Zheng, Gao Tu, Fengyuan Yang, Yu Zong Chen, Xiaojun Yao, Xiaofeng Li, Weiwei Xue, Feng Zhu
Metabotropic glutamate receptor 5 (mGlu5) plays a key role in synaptic information storage and memory, which is a well-known target for a variety of psychiatric and neurodegenerative disorders. In recent years, the increasing efforts have been focused on the design of allosteric modulators, and the negative allosteric modulators (NAMs) are the front runners. Recently, the architecture of transmembrane (TM) domain of mGlu5 receptor has been determined by crystallographic experiment. However, it has been not well understood how the pharmacophores of NAMs accommodated into the allosteric binding site...
March 9, 2018: ACS Chemical Neuroscience
Andrea Boente Juncal, Aida G Mendez, Carmen Vale, Mercedes R Vieytes, Luis M Botana
Spirolides are marine toxins, produced by dinoflagellates that act as potent antagonists of nicotinic acetylcholine receptors. These compounds are not toxic for humans and since there are no reports of human intoxications caused by this group of toxins they are not yet currently regulated in Europe. Currently 13-desmethyl spirolide C, 13,19-didesmethyl spirolide C and 20-methyl spirolide G are commercially available as reference materials. Previous work in our laboratory has demonstrated that after 4 days of treatment of primary mice cortical neurons with 13-desmethyl spirolide C, the compound ameliorated the glutamate induced toxicity and increased acetylcholine levels and the expression of the acetylcholine synthesizing enzyme being useful both in vitro and in vivo to decrease the brain pathology associated with Alzheimer´s disease...
March 8, 2018: ACS Chemical Neuroscience
Julie Sadino, Zoe Donaldson
Over a lifetime, humans build relationships with family, friends, and partners that are critically important for our mental and physical health. Unlike commonly used laboratory mice and rats, Microtine rodents provide a unique model to study the neurobiology underlying pair bonding and the selective attachments that form between adults. Comparisons between monogamous prairie voles and the closely related, but non-monogamous meadow and montane voles, have revealed that brain-region-specific neuropeptide receptor patterning modulates social behavior between and within species...
March 7, 2018: ACS Chemical Neuroscience
Kerry L Price, Sarah C R Lummis
Cys-loop receptors are major sites of action for many important therapeutically active compounds, but the sites of action of those that do not act at the orthosteric binding site or at the pore are mostly poorly understood. To help understand these, we here describe a chimeric receptor consisting of the extracellular domain of the 5-HT3 A receptor and the transmembrane domain of a prokaryotic homologue, ELIC. Alterations of some residues at the coupling interface are required for function, but the resulting receptor expresses well and responds to 5-HT with a lower EC50 (0...
March 6, 2018: ACS Chemical Neuroscience
Mai H Philipsen, Nhu N T Phan, John Stephen Fletcher, Per Malmberg, Andrew G Ewing
Time-of-flight secondary ion mass spectrometry (ToF-SIMS) was used to study the effects of cocaine versus methylphenidate administration on both the localization and abundance of lipids in Drosophila melanogaster brain. A J105 ToF-SIMS with a 40 keV gas cluster primary ion source enabled us to probe molecular ions of biomolecules in the fly with a spatial resolution around 3 µm, giving us unique insights into the effect of these drugs on molecular lipids in the nervous system. Significant changes in phospholipid composition were observed in the central brain for both...
March 6, 2018: ACS Chemical Neuroscience
Frank Matthes, Serena Massari, Anna Bochicchio, Kenji Schorpp, Judith Schilling, Stephanie Weber, Nina Offermann, Jenny Desantis, Erich E Wanker, Paolo Carloni, Kamyar Hadian, Oriana Tabarrini, Giulia Rossetti, Sybille Krau Szlig
Expanded CAG trinucleotide repeats in Huntington's disease (HD) are causative for neurotoxicity. Not only does the mutant CAG-repeat RNA encode for neurotoxic polyglutamine proteins, but also it can lead to a toxic gain-of-function by aberrantly recruiting RNA-binding proteins. One of these is the MID1 protein, which induces aberrant Huntingtin (HTT) protein translation upon binding. Here we have identified a set of CAG repeat binder candidates by in silico methods. One of those, furamidine, reduces the binding of HTT mRNA to MID1 and other target proteins in vitro...
March 5, 2018: ACS Chemical Neuroscience
Ravi Naik, Heather Valentine, Robert F Dannals, Dean F Wong, Andrew G Horti
New GABAB agonists, fluoropyridyl ether analogues of baclofen, have been synthesized as potential PET radiotracers. The compound with highest inhibition binding affinity as well as greatest agonist response, (R)-4-amino-3-(4-chloro-3-((2-fluoropyridin-4-yl)methoxy)phenyl)butanoic acid (1b), was radiolabeled with18 F with good radiochemical yield, high radiochemical purity, and high molar radioactivity. The regional brain distribution of the radiolabeled (R)-4-amino-3-(4-chloro-3-((2-[18 F]fluoropyridin-4-yl)methoxy)phenyl)butanoic acid, [18 F]1b, was studied in CD-1 male mice...
March 2, 2018: ACS Chemical Neuroscience
Kathryn T Hall, Joseph Loscalzo, Ted Kaptchuk
There is perhaps no more important time in the history of placebos to consider their role in clinical trials and in medicine. Increasingly well-designed pharmaceutical and academic clinical trials testing promising and established drug and surgical interventions have failed to "beat" the placebo response. The collateral damage resulting from these failures is staggering; novel treatments, many with compelling mechanisms of action and promising Phase 2 trial results, never reach the patient, adversely affecting small and large pharma alike...
March 2, 2018: ACS Chemical Neuroscience
Sabine Mogwitz, Judith Buse, Nicole Wolff, Veit Roessner
More than forty years of research and clinical practice have proven the effectiveness of dopamine receptor antagonists in the pharmacological treatment of tics. A blockade of the striatal dopamine-D2 receptors is mainly responsible for their tic-reducing effect. A broad spectrum of dopamine-modulating agents, such as typical and atypical antipsychotics, but also dopamine receptor agonists are used with an immanent discord between experts about which of them should be considered as first choice. The present article outlines the state of the art on pharmacological treatment of tics with dopamine-modulating agents by giving an systemativ overview of studies on their effectiveness and a critical discussion of their specific adverse effects...
March 2, 2018: ACS Chemical Neuroscience
Yaxia Yuan, Jun Zhu, Chang-Guo Zhan
Molecular modeling and molecular dynamics simulations were performed, in the present study, to examine the modes of dopamine binding with human and drosophila dopamine transporters (hDAT and dDAT). The computational data revealed flipped binding orientations of dopamine in hDAT and dDAT due to the major differences in three key residues (S149, G153, and A423 of hDAT vs A117, D121, and S422 of dDAT) in the binding pocket. These three residues dictate the binding orientation of dopamine in the binding pocket, as the aromatic ring of dopamine tends to take an orientation with both the para- and meta-hydroxyl groups being close to polar residues and away from non-polar residues of the protein...
March 1, 2018: ACS Chemical Neuroscience
Daniela Neuhofer, Olivier Lassalle, Olivier Manzoni
We investigated how metabotropic Acetylcholine receptors control excitatory synaptic plasticity in the mouse nucleus accumbens core. Pharmacological and genetic approaches revealed that M1 mAChRs trigger multiple and interacting forms of synaptic plasticity. As previously described in the dorsal striatum, moderate pharmacological activation of M1 mAChR potentiated postsynaptic NMDARs. The M1-potentiation of NMDAR masked a previously unknown coincident TRPV1-mediated long-term depression (LTD). In addition, strong pharmacological activation of M1 mAChR induced canonical retrograde LTD, mediated by presynaptic CB1R...
February 28, 2018: ACS Chemical Neuroscience
Jasmin Segelken, Melanie Wallisch, Konrad Schultz, Jens Christoffers, Ulrike Janssen-Bienhold
The vitamin A derivative all-trans-retinoic acid (ATRA) is an important biologically active metabolite that regulates a variety of essential biological processes in particular via gene-regulatory mechanisms. In the retina, ATRA is a light-dependent byproduct of the phototransduction cascade. Here, ATRA is not only needed for proper retinal development, but it also acts as a neuromodulator on horizontal cells, second-order inhibitory neurons in the outer retina, which reveal morphological and physiological changes when the retina is treated with ATRA...
February 26, 2018: ACS Chemical Neuroscience
Anqi Wang, Jiesi Feng, Yulong Li, Peng Zou
Optical biosensors have been invaluable tools in neuroscience research, as they provide the ability to directly visualize neural activity in real time, with high specificity, and with exceptional spatial and temporal resolution. Notably, a majority of these sensors are based on fluorescent protein scaffolds, which offer the ability to target specific cell types or even subcellular compartments. However, fluorescent proteins are intrinsically bulky tags, often insensitive to the environment, and always require excitation light illumination...
February 26, 2018: ACS Chemical Neuroscience
Rosa Maria Vitale, Vincenzo Rispoli, Doriana Desiderio, Roberta Sgammato, Stefano Thellung, Claudio Canale, Massimo Vassalli, Marianna Carbone, Maria Letizia Ciavatta, Ernesto Mollo, Vera Felicità, Rosaria Arcone, Margherita Gavagnin, Mariorosario Masullo, Tullio Florio, Pietro Amodeo
Multitargeting/polypharmacological approaches, looking for single chemical entities retaining the ability to bind two or more molecular targets, are a potentially powerful strategy to fight complex, multifactorial pathologies. Unfortunately, the search for multiligand agents is challenging, because only a small subset of molecules contained in molecular databases are bioactive, and even fewer are active on a preselected set of multiple targets. However, collections of natural compounds feature a significantly higher fraction of bioactive molecules than synthetic ones...
February 23, 2018: ACS Chemical Neuroscience
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"