Long-Term Potentiation-Associated Gene Expression: Involvement of the Tumour Protein p53

Lisachev, P. D.; Штарк, М. Б.

doi:10.5772/intechopen.73219

Cited by 3 publications

(3 citation statements)

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“…In a preliminary manner, we surveyed the relative level of gene expression that is associated with long-term potentiation (LTP) given this is widely accepted as a cellular mechanism underlying memory processes. However, differences between the STD, HFD, and HF1G groups were not identified when a cadre of LTP-related genes that were reported in the literature [ 24 , 25 , 26 ] were investigated (data not shown). Nonetheless, this work may bear repeating with a more highly powered study design and more refined analysis of temporal sequence.…”

Section: Discussionmentioning

confidence: 99%

Effect of Dietary Grapes on Female C57BL6/J Mice Consuming a High-Fat Diet: Behavioral and Genetic Changes

et al. 2022

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(1) Background: Adverse effects of a chronic high-fat diet (HFD) on murine behavior, cognition, and memory are well established. Polyphenols such as resveratrol, anthocyanins, and flavonoids, that are known for antioxidative and anti-inflammatory properties, are present in grapes. The objective of this work was to determine if the dietary intake of grapes has the potential of alleviating HFD-induced deficiencies. (2) Methods: The effect of dietary grape intake was studied using behavioral assays and high throughput genome-wide RNA transcriptome analyses with female C57BL6/J mice. (3) Results: Mice that were fed a HFD from 3-weeks of age showed anxiety-like behaviors compared with the standard diet (STD). This HFD-induced effect was attenuated by supplementing the HFD with 1% grape powder (HF1G) (open field test). Similar results were observed with the novel object recognition test; there was a significant difference in time spent exploring a novel object between the HFD and the HF1G groups. There was no significant difference between the HFD1G and the STD groups. Based on the RNA-Seq analysis, genetic expression in the brain varied as a result of diet, with 210, 360, and 221 uniquely expressed genes in the STD, HFD, and HF1G groups, respectively. Cluster analysis revealed that the HFIG group mapped more closely with the STD group than the HFD group. Focusing on some specific areas, based on genetic expression, Dopamine receptor 2 (Drd2) was increased in the HFD group and normalized in the HF1G group, relative to the STD group. In addition, as judged by cluster hierarchy, the expression of genes that are associated with the dopamine receptor 2 pathway were increased in the HFD group, whereas the pattern that was derived from mouse brain from the HF1G group showed greater similarity to the STD group. KEGG pathway analyses were consistent with these results. For example, neuroactive ligand-receptor interaction (KEGG ID: mmu04080) was altered due to HFD compared with STD, but normalized by grape supplementation or the HFD; there was no significant difference between the STD and HF1G groups. In addition, the expression of genes related to feeding behavior, such as Adora2a, Th, and Trh, were also increased in the HFD group compared with the STD group, and attenuated by grape supplementation. (4) Conclusions: Dietary grape consumption has positive effects on behavior and cognition that are impaired by a HFD. Attenuation of these effects correlates with global transcriptional changes in mouse brain.

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Section: Discussionmentioning

confidence: 99%

Effect of Dietary Grapes on Female C57BL6/J Mice Consuming a High-Fat Diet: Behavioral and Genetic Changes

et al. 2022

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“…A key challenge in the study of synaptic plasticity is the diversity of LTP/LTD observed across the cell types in the brain ( Granger and Nicoll, 2014 ). Differences in the transcriptome have been proposed as one of the sources for this variability ( Lisachev and Shtark, 2018 ). We believe our model can be used to explain some of the discrepancies in the experimental data in this regard and expand the understanding of possible molecular contributors to LTP/LTD.…”

Section: Discussionmentioning

confidence: 99%

“…Differences in the transcriptome has been proposed as one of the sources for this variability (cf. [Lisachev and Shtark, 2018]). We believe our model can be used to explain some of the discrepancies in the experimental data in this regard and expand the understanding of possible molecular contributors to LTP/LTD.…”

Section: Implications Of the Studymentioning

confidence: 99%

A unified computational model for cortical post-synaptic plasticity

Mäki‐Marttunen

Iannella

Edwards

et al. 2020

eLife

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Signalling pathways leading to post-synaptic plasticity have been examined in many types of experimental studies, but a unified picture on how multiple biochemical pathways collectively shape neocortical plasticity is missing. We built a biochemically detailed model of post-synaptic plasticity describing CaMKII, PKA, and PKC pathways and their contribution to synaptic potentiation or depression. We developed a statistical AMPA-receptor-tetramer model, which permits the estimation of the AMPA-receptor-mediated maximal synaptic conductance based on numbers of GluR1s and GluR2s predicted by the biochemical signalling model. We show that our model reproduces neuromodulator-gated spike-timing-dependent plasticity as observed in the visual cortex and can be fit to data from many cortical areas, uncovering the biochemical contributions of the pathways pinpointed by the underlying experimental studies. Our model explains the dependence of different forms of plasticity on the availability of different proteins and can be used for the study of mental disorder-associated impairments of cortical plasticity.

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A unified computational model for cortical post-synaptic plasticity

Mäki‐Marttunen

Iannella

Edwards

et al. 2020

Preprint

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Cortical synapses possess a machinery of signalling pathways that leads to various modes of post-synaptic plasticity. Such pathways have been examined to a great detail separately in many types of experimental studies. However, a unified picture on how multiple biochemical pathways collectively shape the observed synaptic plasticity in the neocortex is missing. Here, we built a biochemically detailed model of post-synaptic plasticity that includes the major signalling cascades, namely, CaMKII, PKA, and PKC pathways which, upon activation by Ca 2+ , lead to synaptic potentiation or depression. We adjusted model components from existing models of intracellular signalling into a single-compartment simulation framework. Furthermore, we propose a statistical model for the prevalence of different types of membrane-bound AMPA-receptor tetramers consisting of GluR1 and GluR2 subunits in proportions suggested by the biochemical signalling model, which permits the estimation of the AMPA-receptor-mediated maximal synaptic conductance. We show that our model can reproduce neuromodulator-gated spike-timing-dependent plasticity as observed in the visual cortex. Moreover, we demonstrate that our model can be fit to data from many cortical areas and that the resulting model parameters reflect the involvement of the pathways pinpointed by the underlying experimental studies. Our model explains the dependence of different forms of plasticity on the availability of different proteins and can be used for the study of mental disorder-associated impairments of cortical plasticity. Significance statementNeocortical synaptic plasticity has been studied experimentally in a number of cortical areas, showing how interactions between neuromodulators and post-synaptic proteins shape the outcome of the plasticity. On the other hand, non-detailed computational models of long-term plasticity, such as Hebbian rules of synaptic potentiation and depression, have been widely used in modelling of neocortical circuits. In this work, we bridge the gap between these two branches of neuroscience by building a detailed model of post-synaptic plasticity that can reproduce observations on cortical plasticity and provide biochemical meaning to the simple rules of plasticity. Our model can be used for predicting the effects of chemical or genetic manipulations of various intracellular signalling proteins on induction of plasticity in health and disease.

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Long-Term Potentiation-Associated Gene Expression: Involvement of the Tumour Protein p53

Cited by 3 publications

References 83 publications

Effect of Dietary Grapes on Female C57BL6/J Mice Consuming a High-Fat Diet: Behavioral and Genetic Changes

Effect of Dietary Grapes on Female C57BL6/J Mice Consuming a High-Fat Diet: Behavioral and Genetic Changes

A unified computational model for cortical post-synaptic plasticity

A unified computational model for cortical post-synaptic plasticity

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