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proteomics and hippocampus

Daniel V Guebel, Néstor V Torres
Motivation: In the brain of elderly-healthy individuals, the effects of sexual dimorphism and those due to normal aging appear overlapped. Discrimination of these two dimensions would powerfully contribute to a better understanding of the etiology of some neurodegenerative diseases, such as "sporadic" Alzheimer. Methods: Following a system biology approach, top-down and bottom-up strategies were combined. First, public transcriptome data corresponding to the transition from adulthood to the aging stage in normal, human hippocampus were analyzed through an optimized microarray post-processing (Q-GDEMAR method) together with a proper experimental design (full factorial analysis)...
2016: Frontiers in Aging Neuroscience
Dong Ik Park, Carine Dournes, Inge Sillaber, Manfred Uhr, John M Asara, Nils C Gassen, Theo Rein, Marcus Ising, Christian Webhofer, Michaela D Filiou, Marianne B Müller, Christoph W Turck
Selective Serotonin Reuptake Inhibitors (SSRIs) are commonly used drugs for the treatment of psychiatric diseases including major depressive disorder (MDD). For unknown reasons a substantial number of patients do not show any improvement during or after SSRI treatment. We treated DBA/2J mice for 28 days with paroxetine and assessed their behavioral response with the forced swim test (FST). Paroxetine-treated long-time floating (PLF) and paroxetine-treated short-time floating (PSF) groups were stratified as proxies for drug non-responder and responder mice, respectively...
October 12, 2016: Scientific Reports
Chi-Ya Kao, Zhisong He, Kathrin Henes, John M Asara, Christian Webhofer, Michaela D Filiou, Philipp Khaitovich, Carsten T Wotjak, Christoph W Turck
Posttraumatic stress disorder (PTSD) is a prevalent psychiatric disorder. Several studies have attempted to characterize molecular alterations associated with PTSD, but most findings were limited to the investigation of specific cellular markers in the periphery or defined brain regions. In the current study, we aimed to unravel affected molecular pathways/mechanisms in the fear circuitry associated with PTSD. We interrogated a foot shock-induced PTSD mouse model by integrating proteomics and metabolomics profiling data...
May 2016: Molecular Neuropsychiatry
Agata Grazia D'Amico, Grazia Maugeri, Rita Reitano, Sebastiano Cavallaro, Velia D'Agata
PARK2 gene's mutations are related to the familial form of juvenile Parkinsonism, also known as the autosomic recessive juvenile Parkinsonism. This gene encodes for parkin, a 465-amino acid protein. To date, a large number of parkin isoforms, generated by an alternative splicing mechanism, have been described. Currently, Gene Bank lists 27 rat PARK2 transcripts, which matches to 20 exclusive parkin alternative splice variants. Despite the existence of these isoforms, most of the studies carried out so far, have been focused only on the originally cloned parkin...
September 6, 2016: Protein Journal
Zhong-Guo Chen, Xing Liu, Weisheng Wang, Fan Geng, Jing Gao, Chen-Ling Gan, Jing-Rui Chai, Ling He, Gang Hu, Hu Zhou, Jing-Gen Liu
Addiction is characterized by drug craving, compulsive drug taking and relapse, which is attributed to aberrant neuroadaptation in brain regions implicated in drug addiction, induced by changes in gene and protein expression in these regions after chronic drug exposure. Accumulating evidence suggests that the dorsal hippocampus (DH) plays an important role in mediating drug-seeking and drug-taking behavior and relapse. However, the molecular mechanisms underlying these effects of the DH are unclear. In the present study, we employed a label-free quantitative proteomic approach to analyze the proteins altered in the DH of heroin self-administering rats...
August 22, 2016: Addiction Biology
Christian Knöchel, Jonathan Kniep, Jason D Cooper, Michael Stäblein, Sofia Wenzler, Jan Sarlon, David Prvulovic, David E J Linden, Sabine Bahn, Pawel Stocki, Sureyya Ozcan, Gilberto Alves, Andre F Carvalho, Andreas Reif, Viola Oertel-Knöchel
Proteomic analyses facilitate the interpretation of molecular biomarker probes which are very helpful in diagnosing schizophrenia (SZ). In the current study, we attempt to test whether potential differences in plasma protein expressions in SZ and bipolar disorder (BD) are associated with cognitive deficits and their underlying brain structures. Forty-two plasma proteins of 29 SZ patients, 25 BD patients and 93 non-clinical controls were quantified and analysed using multiple reaction monitoring-based triple quadrupole mass spectrometry approach...
August 22, 2016: European Archives of Psychiatry and Clinical Neuroscience
N E Sharanova, N V Kirbaeva, I Yu Toropygin, E V Khryapova, E V Koplik, C Kh Soto, S S Pertsov, A V Vasiliev
We compared proteome profiles of selected brain areas (cortex, amygdala, hippocampus, and reticular formation) and measured cathepsins B and D activity in liver lysosomal fraction in rats with different behavioral activity under conditions of emotional stress. In passive rats, the expression of some proteins in various brain regions was changed and baseline cathepsin B activity was higher than in active animals. Taken together, the results attest to differences in the adaptive response formation in rats, depending on behavioral features...
July 2016: Bulletin of Experimental Biology and Medicine
Srinivas Ayyadevara, Meenakshisundaram Balasubramaniam, Paul A Parcon, Steven W Barger, W Sue T Griffin, Ramani Alla, Alan J Tackett, Samuel G Mackintosh, Emanuel Petricoin, Weidong Zhou, Robert J Shmookler Reis
Neurodegenerative diseases are distinguished by characteristic protein aggregates initiated by disease-specific 'seed' proteins; however, roles of other co-aggregated proteins remain largely unexplored. Compact hippocampal aggregates were purified from Alzheimer's and control-subject pools using magnetic-bead immunoaffinity pulldowns. Their components were fractionated by electrophoretic mobility and analyzed by high-resolution proteomics. Although total detergent-insoluble aggregates from Alzheimer's and controls had similar protein content, within the fractions isolated by tau or Aβ1-42 pulldown, the protein constituents of Alzheimer-derived aggregates were more abundant, diverse, and post-translationally modified than those from controls...
October 2016: Aging Cell
Nikhil J Pandya, Remco V Klaassen, Roel C van der Schors, Johan A Slotman, Adriaan Houtsmuller, August B Smit, Ka Wan Li
The group 1 metabotropic glutamate receptors 1 and 5 have been implicated in mechanisms of synaptic plasticity and may serve as potential therapeutic targets in autism spectrum disorders. The interactome of group 1 mGluRs has remained largely unresolved. Using a knockout-controlled interaction proteomics strategy we examined the mGluR5 protein complex in two brain regions, hippocampus and cortex, and identified mGluR1 as its major interactor in addition to the well-described Homer proteins. We confirmed the presence of mGluR1/5 complex by (1) reverse immunoprecipitation using an mGluR1 antibody to pulldown mGluR5 from hippocampal tissue, (2) co-expression in HEK293 cells followed by co-immunoprecipitation to reveal the direct interaction of mGluR1 and 5, and (3) super-resolution microscopy imaging of hippocampal primary neurons to show co-localization of the mGluR1/5 in the synapse...
July 9, 2016: Proteomics
Hyo Youl Moon, Andreas Becke, David Berron, Benjamin Becker, Nirnath Sah, Galit Benoni, Emma Janke, Susan T Lubejko, Nigel H Greig, Julie A Mattison, Emrah Duzel, Henriette van Praag
Peripheral processes that mediate beneficial effects of exercise on the brain remain sparsely explored. Here, we show that a muscle secretory factor, cathepsin B (CTSB) protein, is important for the cognitive and neurogenic benefits of running. Proteomic analysis revealed elevated levels of CTSB in conditioned medium derived from skeletal muscle cell cultures treated with AMP-kinase agonist AICAR. Consistently, running increased CTSB levels in mouse gastrocnemius muscle and plasma. Furthermore, recombinant CTSB application enhanced expression of brain-derived neurotrophic factor (BDNF) and doublecortin (DCX) in adult hippocampal progenitor cells through a mechanism dependent on the multifunctional protein P11...
August 9, 2016: Cell Metabolism
Ke Cheng, Juan Li, Deyu Yang, Yongtao Yang, Chenglong Rao, Shuxiao Zhang, Wei Wang, Hua Guo, Liang Fang, Dan Zhu, Yu Han, Peng Xie
Major depression is a devastating psychiatric disease worldwide currently. A reduced olfactory sensitivity in MDD patients was well evidenced. We previously interrogated the mechanism of decreasing hippocampus neurogenesis in CUMS rat model of depression. The Olfactory Bulb (OB) is crucial part of the olfactory system which functions in post-developmental neurogenesis. However, the mechanism of the dysfunction of OB induced by CUMS is still largely unknown. Herein, by using the chronic unpredictable mild stress (CUMS) rat model of depression, differential protein expression between the OB proteomes of CUMS and control group was interrogated through two-dimensional electrophoresis coupling with matrix-assisted laser desorption ionization-time of flight tandem mass spectrometry...
October 15, 2016: Behavioural Brain Research
Fanomezana M Ranaivoson, Sventja von Daake, Davide Comoletti
Reelin is a neuronal glycoprotein secreted by the Cajal-Retzius cells in marginal regions of the cerebral cortex and the hippocampus where it plays important roles in the control of neuronal migration and the formation of cellular layers during brain development. This 3461 residue-long protein is composed of a signal peptide, an F-spondin-like domain, eight Reelin repeats (RR1-8), and a positively charged sequence at the C-terminus. Biochemical data indicate that the central region of Reelin binds to the low-density lipoprotein receptors apolipoprotein E receptor 2 (ApoER2) and the very-low-density lipoprotein receptor (VLDLR), leading to the phosphorylation of the intracellular adaptor protein Dab1...
2016: Frontiers in Cellular Neuroscience
Hongsheng Zhang, Eunchai Kang, Yaqing Wang, Chaojuan Yang, Hui Yu, Qin Wang, Zheyu Chen, Chen Zhang, Kimberly M Christian, Hongjun Song, Guo-Li Ming, Zhiheng Xu
Several genome- and proteome-wide studies have associated transcription and translation changes of CRMP2 (collapsing response mediator protein 2) with psychiatric disorders, yet little is known about its function in the developing or adult mammalian brain in vivo. Here we show that brain-specific Crmp2 knockout (cKO) mice display molecular, cellular, structural and behavioural deficits, many of which are reminiscent of neural features and symptoms associated with schizophrenia. cKO mice exhibit enlarged ventricles and impaired social behaviour, locomotor activity, and learning and memory...
June 1, 2016: Nature Communications
H Scott Swartzwelder, Mary-Louise Risher, Kelsey M Miller, Roger J Colbran, Danny G Winder, Tiffany A Wills
Adolescent alcohol use is the strongest predictor for alcohol use disorders. In rodents, adolescents have distinct responses to acute ethanol, and prolonged alcohol exposure during adolescence can maintain these phenotypes into adulthood. One brain region that is particularly sensitive to the effects of both acute and chronic ethanol exposure is the hippocampus. Adolescent intermittent ethanol exposure (AIE) produces long lasting changes in hippocampal synaptic plasticity and dendritic morphology, as well as in the susceptibility to acute ethanol-induced spatial memory impairment...
2016: PloS One
Rachel E Neal, Rekha Jagadapillai, Jing Chen, Cindy Webb, Kendall Stocke, Robert M Greene, M Michele Pisano
Exposure to cigarette smoke during development is linked to neurodevelopmental delays and cognitive impairment including impulsivity, attention deficit disorder, and lower IQ. Utilizing a murine experimental model of "active" inhalation exposure to cigarette smoke spanning the entirety of gestation and through human third trimester equivalent hippocampal development [gestation day 1 (GD1) through postnatal day 21 (PD21)], we examined hippocampus proteome and metabolome alterations present at a time during which developmental cigarette smoke exposure (CSE)-induced behavioral and cognitive impairments are evident in adult animals from this model system...
May 18, 2016: Reproductive Toxicology
Bruce C Kennedy, Jiva G Dimova, Srikanth Dakoji, Li-Lian Yuan, Jonathan C Gewirtz, Phu V Tran
The mounting of appropriate emotional and neuroendocrine responses to environmental stressors critically depends on the hypothalamic-pituitary-adrenal (HPA) axis and associated limbic circuitry. Although its function is currently unknown, the highly evolutionarily conserved transmembrane protein 35 (TMEM35) is prominently expressed in HPA circuitry and limbic areas, including the hippocampus and amygdala. To investigate the possible involvement of this protein in neuroendocrine function, we generated tmem35 knockout (KO) mice to characterize the endocrine, behavioral, electrophysiological, and proteomic alterations caused by deletion of the tmem35 gene...
July 1, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Justin R King, Nadine Kabbani
Nicotinic acetylcholine receptors (nAChRs) modulate the growth and structure of neurons throughout the nervous system. Ligand stimulation of the α7 nAChR has been shown to regulate the large heterotrimeric GTP-binding protein (G protein) signaling in various types of cells. Here, we demonstrate a role for α7 nAChR/G protein interaction in the activation of the small (monomeric) RhoA GTPase leading to cytoskeletal changes during neurite growth. Treatment of PC12 cells with the α7 nAChR agonist choline or PNU-282987 was associated with an increase in RhoA activity and an inhibition in neurite growth...
August 2016: Journal of Neurochemistry
Xiaoning Sun, Ning Shi, Ying Li, Chunyan Dong, Maolin Zhang, Zhenhong Guan, Ming Duan
It is well established now that neuronal dysfunction rather than structural damage may be responsible for the development of rabies. In order to explore the underlying mechanisms in rabies virus (RABV) and synaptic dysfunctions, a quantitative proteome profiling was carried out on synaptosome samples from mice hippocampus. Synaptosome samples from mice hippocampus were isolated and confirmed by Western blot and transmission electron microscopy. Synaptosome protein content changes were quantitatively detected by Nano-LC-MS/MS...
September 2016: Current Microbiology
Stefan J Kempf, Athanasios Metaxas, María Ibáñez-Vea, Sultan Darvesh, Bente Finsen, Martin R Larsen
The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. We report that signalling pathways related to synaptic functions associated with dendritic spine morphology, neurite outgrowth, long-term potentiation, CREB signalling and cytoskeletal dynamics were altered in 12 month old APPswe/PS1ΔE9 mice, particularly in the neocortex and olfactory bulb...
June 7, 2016: Oncotarget
Joseph L Bundy, Brian D Inouye, Roger S Mercer, Richard S Nowakowski
An assessment of fractionated mouse hippocampal peptides was conducted. Protein extract from a single mouse hippocampus was enzymatically digested and fractionated by IEF. Aliquots of fractions were pooled into fewer, more complex samples. The unfractionated lysate, fractions, and pooled fractions were subjected to LC-MS/MS analysis. Samples consisting of many individual fractions had more protein identifications, greater protein sequence coverage, and quantified proteins with more spectral counts than protein extract that was unfractionated or pooled into fewer LC-MS/MS samples...
July 2016: Electrophoresis
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