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proteomics and hippocampus

Paul R Evans, Kyle J Gerber, Eric B Dammer, Duc M Duong, Devrishi Goswami, Daniel J Lustberg, Juan Zou, Jenny J Yang, Serena M Dudek, Patrick R Griffin, Nicholas T Seyfried, John R Hepler
Regulator of G Protein Signaling 14 (RGS14) is a complex scaffolding protein that integrates G protein and MAPK signaling pathways. In the adult mouse brain, RGS14 is predominantly expressed in hippocampal CA2 neurons where it naturally inhibits synaptic plasticity and hippocampus-dependent learning and memory. However, the signaling proteins that RGS14 natively engages to regulate plasticity are unknown. Here, we show that RGS14 exists in a high molecular weight protein complex in brain. To identify RGS14 neuronal interacting partners, endogenous RGS14 immunoprecipitated from mouse brain was subjected to mass spectrometry and proteomic analysis...
March 8, 2018: Journal of Proteome Research
Rachael E Wilson, Andrea Jaquins-Gerstl, Stephen G Weber
We have developed a method for online collection and quantitation of neuropeptides in rat brain microdialysates using on-column dimethylation with capillary liquid chromatography - tandem mass spectrometry (cLC - MS2). This method addresses a number of the challenges of quantifying neuropeptides with cLC - MS. It is also a completely automated and robust method for the preparation of stable isotope labeled - peptide internal standards to correct for matrix effects and thus ensure accurate quantitation. Originally developed for tissue-derived proteomics samples (Raijmakers, et al...
March 5, 2018: Analytical Chemistry
Maree J Webster, Sanghyeon Kim
The Stanley Medical Research Institute Brain Collection distributes samples from specified cohorts that contain demographically matched groups of subjects with mental illnesses such as schizophrenia, bipolar disorder, and major depression, as well as unaffected controls. The groups are matched by age, sex, race, postmortem interval, pH, side of brain, and mRNA quality. The samples are distributed coded so that all data must be returned in order to obtain the demographic information. The database contains more than 5000 individual data sets, as well as data from high-throughput microarray, sequencing, and proteomic studies...
2018: Handbook of Clinical Neurology
A Schrötter, A Oberhaus, K Kolbe, S Seger, T Mastalski, F El Magraoui, E Hoffmann-Posorske, M Bohnert, J Deckert, C Braun, M Graw, C Schmitz, T Arzberger, C Loosse, H Heinsen, H E Meyer, T Müller
No abstract text is available yet for this article.
February 8, 2018: Biochimica et Biophysica Acta
Michael Keck, Roelof Maarten van Dijk, Cornelia A Deeg, Katharina Kistler, Andreas Walker, Eva-Lotta von Rüden, Vera Russmann, Stefanie M Hauck, Heidrun Potschka
Information about epileptogenesis-associated changes in protein expression patterns is of particular interest for future selection of target and biomarker candidates. Bioinformatic analysis of proteomic data sets can increase our knowledge about molecular alterations characterizing the different phases of epilepsy development following an initial epileptogenic insult. Here, we report findings from a focused analysis of proteomic data obtained for the hippocampus and parahippocampal cortex samples collected during the early post-insult phase, latency phase, and chronic phase of a rat model of epileptogenesis...
April 2018: Neurobiology of Disease
Katie L Davis-Anderson, Hendrik Wesseling, Lara M Siebert, Emilie R Lunde-Young, Vishal D Naik, Hanno Steen, Jayanth Ramadoss
Fetal alcohol spectrum disorders (FASD) describe neurodevelopmental deficits in children exposed to alcohol in utero. We hypothesized that gestational alcohol significantly alters fetal brain regional protein signature. Pregnant rats were binge-treated with alcohol or pair-fed and nutritionally-controlled. Mass spectrometry identified 1,806, 2,077, and 1,456 quantifiable proteins in the fetal hippocampus, cortex, and cerebellum, respectively. A stronger effect of alcohol exposure on the hippocampal proteome was noted: over 600 hippocampal proteins were significantly (P < 0...
January 31, 2018: Reproductive Toxicology
Stanislav Sutovsky, Tomas Smolek, Peter Turcani, Robert Petrovic, Petra Brandoburova, Santosh Jadhav, Petr Novak, Johannes Attems, Norbert Zilka
The majority (~ 55%) of early onset familial Alzheimer disease (FAD) is caused by mutations in the presenilin 1 gene (PSEN1). Here, we describe a family with early onset FAD with a missense mutation in the PSEN1 gene (Thr116Asn). Five family members developed dementia in the third decade of life. One subject underwent autopsy. The onset of clinical symptoms was at the age of 37 years and the disease progressed rapidly. The clinical picture was characterised by progressive memory impairment, amnestic aphasia, and gait disturbances...
February 5, 2018: Journal of Neural Transmission
Haitao Yu, Dian Wang, Liangyu Zou, Zaijun Zhang, Hua Xu, Feiqi Zhu, Xiaohu Ren, Benhong Xu, Jianhui Yuan, Jianjun Liu, Peter S Spencer, Xifei Yang
Excessive copper intake can lead to neurotoxicity, but there is a lack of comprehensive understanding on the potential impact of copper exposure especially at a low-dose on brain. We used 3xTg-AD mice to explore the potential neurotoxicity of chronic, low-dose copper treatment (0.13 ppm copper chloride in drinking water) on behavior and the brain hippocampal mitochondrial and nuclear proteome. Low-dose copper increased the spatial memory impairment of these animals, increased accumulation of intracellular amyloid 1-42 (Aβ1-42), decreased ATP content, increased the positive staining of 8-hydroxyguanosine (8-OHdG), a marker of DNA oxidative damage, and caused apoptosis and a decrease in synaptic proteins...
January 30, 2018: Archives of Toxicology
Zahra Dargaei, Jee Yoon Bang, Vivek Mahadevan, C Sahara Khademullah, Simon Bedard, Gustavo Morrone Parfitt, Jun Chul Kim, Melanie A Woodin
Huntington's disease (HD) is classically characterized as a movement disorder, however cognitive impairments precede the motor symptoms by ∼15 y. Based on proteomic and bioinformatic data linking the Huntingtin protein (Htt) and KCC2, which is required for hyperpolarizing GABAergic inhibition, and the important role of inhibition in learning and memory, we hypothesized that aberrant KCC2 function contributes to the hippocampal-associated learning and memory deficits in HD. We discovered that Htt and KCC2 interact in the hippocampi of wild-type and R6/2-HD mice, with a decrease in KCC2 expression in the hippocampus of R6/2 and YAC128 mice...
January 30, 2018: Proceedings of the National Academy of Sciences of the United States of America
Dong Kyu Kim, Joonho Park, Dohyun Han, Jinhee Yang, Ahbin Kim, Jongmin Woo, Youngsoo Kim, Inhee Mook-Jung
BACKGROUND: Alzheimer's disease (AD), the most common neurodegenerative disorder, is characterized by the deposition of extracellular amyloid plaques and intracellular neurofibrillary tangles. To understand the pathological mechanisms underlying AD, developing animal models that completely encompass the main features of AD pathologies is indispensable. Although mouse models that display pathological hallmarks of AD (amyloid plaques, neurofibrillary tangles, or both) have been developed and investigated, a systematic approach for understanding the molecular characteristics of AD mouse models is lacking...
January 16, 2018: Molecular Neurodegeneration
Wenyan Han, Huiqing Wang, Jun Li, Shizhong Zhang, Wei Lu
In the brain, AMPA receptors (AMPARs)-mediated excitatory synaptic transmission is critically regulated by the receptor auxiliary subunits. Recent proteomic studies have identified that Ferric Chelate Reductase 1 Like protein (FRRS1L), whose mutations in human lead to epilepsy, choreoathetosis, and cognitive deficits, is present in native AMPAR complexes in the brain. Here we have characterized FRRS1L in both heterologous cells and in mouse neurons. We found that FRRS1L interacts with both GluA1 and GluA2 subunits of AMPARs, but does not form dimers/oligomers, in HEK cells...
2017: Frontiers in Molecular Neuroscience
Guido N Vacano, David S Gibson, Abdullah Arif Turjoman, Jeremy W Gawryluk, Jonathan D Geiger, Mark Duncan, David Patterson
This study was designed to investigate the brain proteome of the Ts65Dn mouse model of Down syndrome. We profiled the cerebellum and hippocampus proteomes of 6- and 12-month-old trisomic and disomic mice by difference gel electrophoresis. We quantified levels of 2082 protein spots and identified 272 (170 unique UniProt accessions) by mass spectrometry. Four identified proteins are encoded by genes trisomic in the Ts65Dn mouse. Three of these (CRYZL11, EZR, and SOD1) were elevated with p-value <0.05, and 2 proteins encoded by disomic genes (MAPRE3 and PHB) were reduced...
November 26, 2017: Neurobiology of Aging
Yuqing Zhang, Shuai Yuan, Juncai Pu, Lining Yang, Xinyu Zhou, Lanxiang Liu, Xiaofeng Jiang, Hanping Zhang, Teng Teng, Lu Tian, Peng Xie
Major depressive disorder (MDD) is a prevalent and serious mental disorder with high rates of suicide and disability. However, the underlying pathogenesis of MDD is complicated and remains largely unclear. An integrated analysis of multiple types of omics data may improve comprehensive understanding of the entire molecular mechanism of MDD. In this study, we applied an integrated analysis of gas chromatography/mass spectrometry (GC-MS)-based metabolomics and isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics to investigate changes in the hippocampus in the chronic unpredictable mild stress (CUMS) rat model of depression...
February 10, 2018: Neuroscience
Hongik Hwang, Hyewhon Rhim
Post-translational modifications (PTMs) covalently modify proteins and diversify protein functions. Along with protein phosphorylation, another common PTM is the addition of O-linked β-N-acetylglucosamine (O-GlcNAc) to serine and/or threonine residues. O-GlcNAc modification is similar to phosphorylation in that it occurs to serine and threonine residues and cycles on and off with a similar time scale. However, a striking difference is that the addition and removal of the O-GlcNAc moiety on all substrates are mediated by the two enzymes regardless of proteins, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively...
March 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Sucharita M Dutta, Melissa M Hadley, Scott Peterman, Jessica S Jewell, Vania D Duncan, Richard A Britten
NASA is planning future missions to Mars, which will result in astronauts being exposed to ∼13 cGy/year of galactic cosmic radiation (GCR). Previous ground-based experiments have demonstrated that low (15 cGy) doses of 1 GeV/n56 Fe ions impair hippocampus-dependent spatial memory in rats. However, some irradiated rats maintain a spatial memory performance comparable to that seen in the sham-irradiated rats, suggesting that some of these animals are able to ameliorate the deleterious effects of the GCR, while others are not...
February 2018: Radiation Research
Lulin Nie, Junxia Xia, Honglian Li, Zaijun Zhang, Ying Yang, Xinfeng Huang, Zhendan He, Jianjun Liu, Xifei Yang
Alzheimer's disease (AD) is one of the most common neurodegenerative diseases, so far, there are no effective measures to prevent and cure this deadly condition. Ginsenoside Rg1 (Rg1) was shown to improve behavioral abnormalities in AD; however, the potential mechanisms remain unclear. In this study, we pretreated 7-month-old 3xTg-AD mice for 6 weeks with Rg1 and evaluated the effects of Rg1 on the behaviors and the protein expression of hippocampal tissues. The behavioral tests showed that Rg1 could improve the memory impairment and ameliorate the depression-like behaviors of 3xTg-AD mice...
2017: Oxidative Medicine and Cellular Longevity
Hongxia Zhao, Hongli Du, Min Liu, Songyan Gao, Na Li, Yufan Chao, Ruiqing Li, Wei Chen, Ziyang Lou, Xin Dong
Vascular depression (VD), a subtype of depression, is caused by vascular diseases or cerebrovascular risk factors. Recently, the proportion of VD patients has increased significantly, which severely affects their quality of life. However, the current pathogenesis of VD has not yet been fully understood, and the basic research is not adequate. In this study, on the basis of the combination of LC-MS-based proteomics and metabolomics, we aimed to establish a protein metabolism regulatory network in a murine VD model to elucidate a more comprehensive impact of VD on organisms...
January 5, 2018: Journal of Proteome Research
Ana Contreras, Lidia Morales, Ali Tebourbi, Miguel Miguéns, Nuria Del Olmo, Carmen Pérez-García
Alcohol consumption during adolescence is deleterious to the developing brain and leads to persistent deficits in adulthood. Several results provide strong evidence for ethanol-associated alterations in glutamatergic signaling and impaired synaptic plasticity in the hippocampus. Protein phosphorylation is a well-known and well-documented mechanism in memory processes, but information on phosphoprotein alterations in hippocampus after ethanol exposure is limited. This study focuses on age-related changes in the hippocampal phosphoproteome after acute alcohol administration...
December 18, 2017: Chemical Research in Toxicology
Laura Hui-Ru Tan, Angela Jin-Rong Tan, Yu-Ying Ng, John Jia-En Chua, Wee-Siong Chew, Sneha Muralidharan, Federico Torta, Bamaprasad Dutta, Siu Kwan Sze, Deron R Herr, Wei-Yi Ong
Sphingomyelinases are a family of enzymes that hydrolyze sphingomyelin to generate phosphocholine and ceramide. The brain distribution and function of neutral sphingomyelinase 2 (nSMase2) were elucidated in this study. nSMase2 mRNA expression was greatest in the striatum, followed by the prefrontal cortex, hippocampus, cerebellum, thalamus, brainstem, and olfactory bulb. The striatum had the highest level of nSMase2 protein expression, followed by the prefrontal cortex, thalamus, hippocampus, brainstem, and cerebellum...
October 17, 2017: Molecular Neurobiology
Waluga Plaingam, Siriporn Sangsuthum, Wannee Angkhasirisap, Tewin Tencomnao
Potentially useful in the treatment of neurodegenerative disorders, Kaempferia parviflora and Myristica fragrans have been shown to possess a wide spectrum of neuropharmacological activities and neuroprotective effects in vivo and in vitro. In this study, we determined whether and how K. parviflora ethanolic extract and M. fragrans volatile oil could influence the levels of neurotransmitters and the whole proteomic profile in the hippocampus of Sprague Dawley (SD) rats. The effects of K. parviflora and M...
October 2017: Journal of Traditional and Complementary Medicine
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