Multi-Omics Analysis Reveals Myelin, Presynaptic and Nicotinate Alterations in the Hippocampus of G72/G30 Transgenic Mice

Filiou, Michaela D.; Teplytska, Larysa; Nussbaumer, Markus; Otte, David-M.; Zimmer, Andreas; Turck, Christoph W.

doi:10.3390/jpm12020244

Cited by 4 publications

(3 citation statements)

References 55 publications

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“…Finally, a very recent multi-omics study revealed “decreased expression of myelin-related proteins” and NAD-dependent protein deacetylase sirtuin-2 (Sirt2), as well as increased expression of the scaffolding presynaptic proteins bassoon (Bsn) and piccolo (Pclo) and the cytoskeletal protein plectin (Plec1) in G72Tg compared to wild-type mice, coupled to a significant decrease of nicotinate levels (a precursor of NAD(P) cofactors) [ 53 ]. Hypomyelination has been reported in SZ, as well as synaptic alterations, including changes in presynaptic neurotransmitter release and post-synaptic characteristics.…”

Section: Putative Biological Roles Of Plg72mentioning

confidence: 99%

Biochemical Properties and Physiological Functions of pLG72: Twenty Years of Investigations

et al. 2022

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In 2002, the novel human gene G72 was associated with schizophrenia susceptibility. This gene encodes a small protein of 153 amino acids, named pLG72, which represents a rare case of primate-specific protein. In particular, the rs2391191 single nucleotide polymorphism (resulting in in the R30K substitution) was robustly associated to schizophrenia and bipolar disorder. In this review, we aim to summarize the results of 20 years of biochemical investigations on pLG72. The main known role of pLG72 is related to its ability to bind and inactivate the flavoenzyme d-amino acid oxidase, i.e., the enzyme that controls the catabolism of d-serine, the main NMDA receptor coagonist in the brain. pLG72 was proposed to target the cytosolic form of d-amino acid oxidase for degradation, preserving d-serine and protecting the cell from oxidative stress generated by hydrogen peroxide produced by the flavoenzyme reaction. Anyway, pLG72 seems to play additional roles, such as affecting mitochondrial functions. The level of pLG72 in the human body is still a controversial issue because of its low expression and challenging detection. Anyway, the intriguing hypothesis that pLG72 level in blood could represent a suitable marker of Alzheimer’s disease progression (a suggestion not sufficiently established yet) merits further investigations.

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Section: Putative Biological Roles Of Plg72mentioning

confidence: 99%

Biochemical Properties and Physiological Functions of pLG72: Twenty Years of Investigations

et al. 2022

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“…Previous complementary proteomics studies from the cerebellum of G72 mice revealed altered protein expression in mitochondria-associated, myelin-and oxidative stress-related processes in G72 compared to control mice [8][9][10][11]. Recently, Filiou et al (2022) performed multi-omics approaches, i.e., quantitative proteomics and metabolomics, from the hippocampus of male, eight weeks old G72 vs. control mice [10]. However, we are still lacking detailed information about both sex-and brain-region specific differences in transcriptome profiles from schizophrenia mouse models such as G72.…”

Section: Objectivementioning

confidence: 99%

Sex-specific cortical, hippocampal and thalamic whole genome transcriptome data from controls and a G72 schizophrenia mouse model

Papazoglou,

Henseler,

Weickhardt

et al. 2024

BMC Res Notes

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Objectives The G72 mouse model of schizophrenia represents a well-known model that was generated to meet the main translational criteria of isomorphism, homology and predictability of schizophrenia to a maximum extent. In order to get a more detailed view of the complex etiopathogenesis of schizophrenia, whole genome transcriptome studies turn out to be indispensable. Here we carried out microarray data collection based on RNA extracted from the retrosplenial cortex, hippocampus and thalamus of G72 transgenic and wild-type control mice. Experimental animals were age-matched and importantly, both sexes were considered separately. Data description The isolated RNA from all three brain regions was purified, quantified und quality controlled before initiation of the hybridization procedure with SurePrint G3 Mouse Gene Expression v2 8 × 60 K microarrays. Following immunofluorescent measurement und preprocessing of image data, raw transcriptome data from G72 mice and control animals were extracted and uploaded in a public database. Our data allow insight into significant alterations in gene transcript levels in G72 mice and enable the reader/user to perform further complex analyses to identify potential age-, sex- and brain-region-specific alterations in transcription profiles and related pathways. The latter could facilitate biomarker identification and drug research and development in schizophrenia research.

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“…Metabolomics studies have been widely implemented in preclinical and clinical neuropsychiatric research [ 67 , 68 ], including, among others, anxiety disorders [ 69 ], post-traumatic stress disorder [ 70 ] and depression [ 71 ]. We have previously used metabolomics approaches to study altered molecular profiles in mouse models of schizophrenia-like symptoms [ 72 ] and high anxiety-related behavior [ 73 - 75 ]. We have also looked for metabolome alterations upon treatment with compounds with antidepressant [ 76 - 79 ] and anxiolytic [ 80 ] properties in mice.…”

Section: Metabolomics and Psychopathologiesmentioning

confidence: 99%

Deciphering the Metabolome under Stress: Insights from Rodent Models

Papageorgiou

Theodoridou

Nussbaumer

et al. 2024

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Despite intensive research efforts to understand the molecular underpinnings of psychological stress and stress responses, the underlying molecular mechanisms remain largely elusive. Towards this direction, a plethora of stress rodent models have been established to investigate the effects of exposure to different stressors. To decipher affected molecular pathways in a holistic manner in these models, metabolomics approaches addressing altered, small molecule signatures upon stress exposure in a high-throughput, quantitative manner provide insightful information on stress-induced systemic changes in the brain. In this review, we discuss stress models in mice and rats, followed by mass spectrometry (MS) and nuclear magnetic resonance (NMR) metabolomics studies. We particularly focus on acute, chronic and early life stress paradigms, highlight how stress is assessed at the behavioral and molecular levels and focus on metabolomic outcomes in the brain and peripheral material such as plasma and serum. We then comment on common metabolomics patterns across different stress models and underline the need for unbiased -omics methodologies and follow-up studies of metabolomics outcomes to disentangle the complex pathobiology of stress and pertinent psychopathologies.

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Multi-Omics Analysis Reveals Myelin, Presynaptic and Nicotinate Alterations in the Hippocampus of G72/G30 Transgenic Mice

Cited by 4 publications

References 55 publications

Biochemical Properties and Physiological Functions of pLG72: Twenty Years of Investigations

Biochemical Properties and Physiological Functions of pLG72: Twenty Years of Investigations

Sex-specific cortical, hippocampal and thalamic whole genome transcriptome data from controls and a G72 schizophrenia mouse model

Deciphering the Metabolome under Stress: Insights from Rodent Models

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