Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Tyrosine kinase inhibitors (TKIs), which have been developed and approved for cancer treatment in the last few years, are involved in synaptic plasticity of learning and memory. Epigenetic modifications also play crucial roles in the process of learning and memory, but its relationship with TKI-induced learning and memory impairment has not been investigated. We hypothesized that LPM4870108, an effective anti-cancer Trk inhibitor, might affect the learning and memory via epigenetic modifications. In this study, rats were orally administered with LPM4870108 (0, 1.25, 2.5, or 5.0 mg/kg) twice daily for 28 days, after which animals were subjected to a Morris water maze test. LPM4870108 exposure caused learning and memory impairments in this test in a dose-dependent manner and reduced the spine densities. Whole-genome transcriptomic analysis revealed significant differences in the patterns of hippocampal gene expression in LPM4870108-treated rats. These transcriptomic data were combined with next-generation bisulfite sequencing analysis, after which RT-PCR and pyrosequencing were conducted, revealing epigenetic alterations associated with genes (Snx8, Fgfr1, Dusp4, Vav2, and Satb2) known to regulate learning and memory. Increased mRNA and protein expression levels of hippocampal Dnmt1 and Dnmt3a were also observed in these rats. Overall, these data suggest that gene-specific alterations in patterns of DNA methylation can potentially contribute to the incidence of learning and memory deficits associated with exposure to LPM4870108.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s00204-022-03226-0 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
4-aminopyridine exerts anxiolytic and pro-cognitive effects in mice model of medial prefrontal cortex ischemia.
Metab Brain Dis
September 2025
Department of Neuroscience, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
Brain ischemia is a major global cause of disability, frequently leading to psychoneurological issues. This study investigates the effects of 4-aminopyridine (4-AP) on anxiety, cognitive impairment, and potential underlying mechanisms in a mouse model of medial prefrontal cortex (mPFC) ischemia. Mice with mPFC ischemia were treated with normal saline (NS) or different doses of 4-AP (250, 500, and 1000 µg/kg) for 14 consecutive days.
View Article and Find Full Text PDFBOLD Long-Range Temporal Correlations Reflect Changes in Language and Depression Across Intensive Aphasia Therapy.
Stroke
September 2025
Brain Language Laboratory, Freie Universität Berlin, Germany (A.-T.P.J., M.R.O., A.S., F.P.).
Background: Intensive language-action therapy treats language deficits and depressive symptoms in chronic poststroke aphasia, yet the underlying neural mechanisms remain underexplored. Long-range temporal correlations (LRTCs) in blood oxygenation level-dependent signals indicate persistence in brain activity patterns and may relate to learning and levels of depression. This observational study investigates blood oxygenation level-dependent LRTC changes alongside therapy-induced language and mood improvements in perisylvian and domain-general brain areas.
View Article and Find Full Text PDFMaximizing theoretical and practical storage capacity in single-layer feedforward neural networks.
Front Comput Neurosci
August 2025
Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA, United States.
Artificial neural networks are limited in the number of patterns that they can store and accurately recall, with capacity constraints arising from factors such as network size, architectural structure, pattern sparsity, and pattern dissimilarity. Exceeding these limits leads to recall errors, eventually leading to catastrophic forgetting, which is a major challenge in continual learning. In this study, we characterize the theoretical maximum memory capacity of single-layer feedforward networks as a function of these parameters.
View Article and Find Full Text PDFDeepRNAac4C: a hybrid deep learning framework for RNA N4-acetylcytidine site prediction.
Front Genet
August 2025
Hunan Provincial Key Laboratory of Finance and Economics Big Data Science and Technology, Hunan University of Finance and Economics, Changsha, China.
RNA N4-acetylcytidine (ac4C) is a crucial chemical modification involved in various biological processes, influencing RNA properties and functions. Accurate prediction of RNA ac4C sites is essential for understanding the roles of RNA molecules in gene expression and cellular regulation. While existing methods have made progress in ac4C site prediction, they still struggle with limited accuracy and generalization.
View Article and Find Full Text PDFIdentification of GABBR2 as a diagnostic marker and its association with Aβ in Alzheimer's disease.
Biochem Biophys Rep
June 2025
Department of Public Health, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Background: Synaptic dysfunction and synapse loss occur in Alzheimer's disease (AD). The current study aimed to identify synaptic-related genes with diagnostic potential for AD.
Methods: Differentially expressed genes (DEGs) were overlapped with phenotype-associated module selected through weighted gene co-expression network analysis (WGCNA), and synaptic-related genes.