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proteomics and hippocampus

Shiladitya Mitra, Ghantasala S Sameer Kumar, B Jyothi Lakshmi, Suman Thakur, Satish Kumar
We earlier reported that the male mice lacking the Wdr13 gene ( Wdr13 -/0 ) showed mild anxiety, better memory retention, and up-regulation of synaptic proteins in the hippocampus. With increasing evidences from parallel studies in our laboratory about the possible role of Wdr13 in stress response, we investigated its role in brain. We observed that Wdr13 transcript gets up-regulated in the hippocampus of the wild-type mice exposed to stress. To further dissect its function, we analyzed the behavioral and molecular phenotypes of Wdr13 -/0 mice when subjected to mild chronic psychological stress, namely; mild (attenuated) social isolation...
2018: Frontiers in Molecular Neuroscience
Stephani A Davis, Sheed Itaman, Christopher M Khalid-Janney, Justin A Sherard, James A Dowell, Nigel J Cairns, Michael A Gitcho
Transactive response DNA-binding protein of 43 kDa (TDP-43) functions as a heterogeneous nuclear ribonucleoprotein and is the major pathological protein in frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis/motor neuron disease (ALS/MND). TDP-43 pathology may also be present as a comorbidity in approximately 20-50% of sporadic Alzheimer's disease cases. In a mouse model of MND, full-length TDP-43 increases association with the mitochondria and blocking the TDP-43/mitochondria interaction ameliorates motor dysfunction...
April 30, 2018: Neuroscience Letters
Abhai Kumar, Smita Singh, Ashish Verma, Vijay Nath Mishra
Mild cognitive impairment (MCI) is an intermediate stage of cognitive decline and dementia. The absence of specific diagnostic test for identification of MCI and AD. The current study aims to find proteomics based change in plasma proteins and diffusion tensor imaging (DTI) based white matter changes in MCI for early detection of prodromal Alzheimer's disease. Fifty cases of mild cognitive impairment and age matched control between (55-75 yrs) were screened on basis of Mini Mental State Examination (MMSE). Two dimensional gel electrophoresis and DTI imaging was performed in MCI and age matched control...
April 9, 2018: Neuroscience Letters
Jesvin S Madan, Kanika Gupta, Sumantra Chattarji, Aditi Bhattacharya
Stress is known to cause contrasting patterns of morphological and physiological plasticity in the hippocampus and amygdala. An obligatory cellular process underlying such neural changes is de novo translation and alterations in protein expression. Yet the nature of the translational response to stress in neurons remains largely unexplored. Even less is known about how glia are affected. Using a click-chemistry-based method to label the de novo proteome in live brain slices, we monitored translation in neurons and astrocytes of the basolateral amygdala (BLA) and dorsal hippocampal area CA3 (dCA3) in rats at different time-points after a single 2-hour exposure to immobilization stress...
April 7, 2018: Hippocampus
Anubha Mudawal, Ankita Srivastava, Anshuman Singh, Jai Shankar, Sanjay Yadav, Manisha Mishra, Pradhyumna K Singh, Vinay K Khanna, Devendra Parmar
Proteomic studies were carried out in immature (3 week), adult (18 week) and aged (48 week) rats to understand the age dependent vulnerability to lindane induced neurodegeneration. 2-D and western blot analysis of protein extracts of hippocampus and substantia-nigra isolated from lindane treated rats (2.5 mg/kg; p.o. X 21 days) revealed marked dysregulation in the expression of proteins related to ubiquitin proteasome pathway, antioxidant activity, chaperones, energy metabolism, calcium homeostasis and proteins involved in neurodegeneration...
March 31, 2018: Food and Chemical Toxicology
Amalia Floriou-Servou, Lukas von Ziegler, Luzia Stalder, Oliver Sturman, Mattia Privitera, Anahita Rassi, Alessio Cremonesi, Beat Thöny, Johannes Bohacek
BACKGROUND: Acutely stressful experiences can trigger neuropsychiatric disorders and impair cognitive processes by altering hippocampal function. Although the intrinsic organization of the hippocampus is highly conserved throughout its long dorsal-ventral axis, the dorsal (anterior) hippocampus mediates spatial navigation and memory formation, whereas the ventral (posterior) hippocampus is involved in emotion regulation. To understand the molecular consequences of stress, detailed genome-wide screens are necessary and need to distinguish between dorsal and ventral hippocampal regions...
February 16, 2018: Biological Psychiatry
Ivana Perić, Victor Costina, Andrijana Stanisavljević, Peter Findeisen, Dragana Filipović
Due to the severity of depressive symptoms, there remains a necessity in defining the underlying mechanisms of depression and the precise actions of antidepressants in alleviating these symptoms. Proteomics is a powerful and promising tool for discovering novel pathways of cellular responses to disease and treatment. As chronic social isolation (CSIS) is a valuable animal model for studying depression, we performed a comparative subproteomic study of rat hippocampus to explore the effect of six weeks of CSIS and the therapeutic effect of chronic fluoxetine (Flx) treatment (last three weeks of CSIS; 15 mg/kg/day)...
March 26, 2018: Neuropharmacology
Haitao Yu, Xuemei Lin, Dian Wang, Zaijun Zhang, Yi Guo, Xiaohu Ren, Benhong Xu, Jianhui Yuan, Jianjun Liu, Peter S Spencer, Jian-Zhi Wang, Xifei Yang
Mitochondrial dysfunction is implicated in the pathogenesis of Alzheimer's disease (AD). However, the precise mitochondrial molecular deficits in AD remain poorly understood. Mitochondrial and nuclear proteomic analysis in mature male triple transgenic AD mice (PS1M146V/APPSwe/TauP301L) by two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) coupled with MALDI-TOF-MS/MS, bio-informatics analysis and immunofluorescent staining were performed in this study. In addition to impaired spatial memory impairment and intracellular accumulation of amyloid 1-42 (Aβ1-42 ) in the 3xTg-AD mice, a well-accepted mouse model of the human disease, we also found significantly increased DNA oxidative damage in entorhinal cortex, hippocampal CA1, CA3 and dental gyrus (DG), as evidenced by the positive staining of 8-hydroxyguanosine, a biomarker of mild cognitive impairment early in AD...
2018: Frontiers in Molecular Neuroscience
Lukas M von Ziegler, Nathalie Selevsek, Ry Y Tweedie-Cullen, Eloïse Kremer, Isabelle M Mansuy
The hippocampal formation is a brain structure essential for higher-order cognitive functions. It has a complex anatomical organization and cellular composition, and hippocampal subregions have different properties and functional roles. In this study, we used SWATH-MS to determine whether the proteomes of hippocampus areas CA1 and CA3 can explain the commonalities or specificities of these subregions in basal conditions and after recognition memory. We show that the proteomes of areas CA1 and CA3 are largely different in basal conditions and that differential changes and dynamics in protein expression are induced in these areas after recognition of an object or object location...
March 20, 2018: Cell Reports
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...
April 6, 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...
April 3, 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.
April 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 1806, 2077, and 1456 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 < ...
March 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...
April 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...
February 13, 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
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