scholarly journals Expression Signature of lncRNAs and mRNAs in Sevoflurane-Induced Mouse Brain Injury: Implication of Involvement of Wide Molecular Networks and Pathways

2021 ◽  
Vol 22 (3) ◽  
pp. 1389
Author(s):  
Congshan Jiang ◽  
Thiago Arzua ◽  
Yasheng Yan ◽  
Xiaowen Bai
Keyword(s):  
Mrna Expression ◽  
Expression Profiles ◽  
Risk Groups ◽  
Bioinformatic Analysis ◽  
Brain Cell ◽  
Learning Ability ◽  
Molecular Networks ◽  
Long Term Memory ◽  
Messenger Rnas

Sevoflurane, one of the most commonly used pediatric anesthetics, was found to cause developmental neurotoxicity. To understand specific risk groups and develop countermeasures, a better understanding of its mechanisms is needed. We hypothesize that, as in many other brain degeneration pathways, long non-coding RNAs (lncRNAs) are involved in the sevoflurane-induced neurotoxicity. Postnatal day 7 (PD7) mice were exposed to 3% sevoflurane for 6 h. To quantify neurotoxicity in these mice, we (1) detected neural apoptosis through analysis of caspase 3 expression level and activity and (2) assessed long-term learning ability via the Morris water maze at PD60. To elucidate specific mechanisms, profiles of 27,427 lncRNAs and 18,855 messenger RNAs (mRNAs) in mouse hippocampi were analyzed using microarray assays. Sevoflurane-induced abnormal lncRNA and mRNA expression-associated function pathways were predicted by bioinformatic analysis. We found that sevoflurane induced significant neurotoxicity, causing acute neuroapoptosis and abnormal expression of 148 mRNAs and 301 lncRNAs on PD7 in mouse hippocampus. Additionally, exposed mice exhibited impaired memory on PD60. Bioinformatic analysis predicted that the dysregulated mRNAs, which are highly correlated with their co-expressed dysregulated lncRNAs, might be involved in 34 neurodegenerative signaling pathways (e.g., brain cell apoptosis and intellectual developmental disorder). Our study reveals for the first time that neonatal exposure to 3% sevoflurane induces abnormal lncRNA and mRNA expression profiles. These dysregulated lncRNAs/mRNAs form wide molecular networks that might contribute to various functional neurological disease pathways in the hippocampus, resulting in the observed acute apoptosis and impaired long-term memory.

scholarly journals Deletion of novel protein TMEM35 alters stress-related functions and impairs long-term memory in mice

2016 ◽  
Vol 311 (1) ◽  
pp. R166-R178 ◽  
Author(s):  
Bruce C. Kennedy ◽  
Jiva G. Dimova ◽  
Srikanth Dakoji ◽  
Li-Lian Yuan ◽  
Jonathan C. Gewirtz ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Pathway Analysis ◽  
Transmembrane Protein ◽  
Long Term Potentiation ◽  
Synaptic Proteins ◽  
Molecular Networks ◽  
Long Term Memory ◽  
Term Memory ◽  
Term Potentiation

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. While capable of mounting a normal corticosterone response to restraint stress, KO mice showed elevated basal corticosterone accompanied by increased anxiety-like behavior. The KO mice also displayed impairment of hippocampus-dependent fear and spatial memories. Given the intact memory acquisition but a deficit in memory retention in the KO mice, TMEM35 is likely required for long-term memory consolidation. This conclusion is further supported by a loss of long-term potentiation in the Schaffer collateral-CA1 pathway in the KO mice. To identify putative molecular pathways underlying alterations in plasticity, proteomic analysis of synaptosomal proteins revealed lower levels of postsynaptic molecules important for synaptic plasticity in the KO hippocampus, including PSD95 and N-methyl-d-aspartate receptors. Pathway analysis (Ingenuity Pathway Analysis) of differentially expressed synaptic proteins in tmem35 KO hippocampus implicated molecular networks associated with specific cellular and behavioral functions, including decreased long-term potentiation, and increased startle reactivity and locomotion. Collectively, these data suggest that TMEM35 is a novel factor required for normal activity of the HPA axis and limbic circuitry.

scholarly journals The Contribution of Spatial and Temporal Molecular Networks in the Induction of Long-term Memory and Its Underlying Synaptic Plasticity

2016 ◽  
Vol 3 (3) ◽  
pp. 356-384 ◽  
Author(s):  
Anastasios A. Mirisis ◽  
◽  
Anamaria Alexandrescu ◽  
Thomas J. Carew ◽  
Ashley M. Kopec
Keyword(s):  
Synaptic Plasticity ◽  
Molecular Networks ◽  
Long Term Memory ◽  
Term Memory

scholarly journals The role of microRNAs in learning and long-term memory

2020 ◽  
Vol 24 (8) ◽  
pp. 885-896
Author(s):  
L. N. Grinkevich
Keyword(s):  
Cognitive Processes ◽  
Regulation Of Gene Expression ◽  
Memory Formation ◽  
Learning Ability ◽  
Long Term Memory ◽  
Term Memory ◽  
Microrna Biogenesis ◽  
The Brain

The mechanisms of long-term memory formation and ways to improve it (in the case of its impairment) remain an extremely difficult problem yet to be solved. Over the recent years, much attention has been paid to microRNAs in this regard. MicroRNAs are unique endogenous non-coding RNAs about 22 nucleotides in length; each can regulate translation of hundreds of messenger RNA targets, thereby controlling entire gene networks. MicroRNAs are widely represented in the central nervous system. A large number of studies are currently being conducted to investigate the role of microRNAs in the brain functioning. A number of microRNAs have been shown to be involved in the process of synaptic plasticity, as well as in the long-term memory formation. Disruption of microRNA biogenesis leads to significant cognitive dysfunctions. Moreover, impaired microRNA biogenesis is one of the causes of the pathogenesis of mental disorders, neurodegenerative illnesses and senile dementia, which are often accompanied by deterioration in the learning ability and by memory impairment. Optimistic predictions are made that microRNAs can be used as targets for therapeutic treatment and for diagnosing the above pathologies. The importance of applications related to microRNAs significantly raises interest in studying their functions in the brain. Thus, this review is focused on the role of microRNAs in cognitive processes. It describes microRNA biogenesis and the role of miRNAs in the regulation of gene expression, as well as the latest achievements in studying the functional role of microRNAs in learning and in long-term memory formation, depending on the activation or inhibition of their expression. The review presents summarized data on the effect of impaired microRNA biogenesis on long-term memory formation, including those associated with sleep deprivation. In addition, analysis is provided of the current literature related to the prospects of improving cognitive processes by influencing microRNA biogenesis via the use of CRISPR/Cas9 technologies and active mental and physical exercises.

scholarly journals A reconstituted mammalian APC-kinesin complex selectively transports defined packages of axonal mRNAs

2020 ◽  
Vol 6 (11) ◽  
pp. eaaz1588 ◽  
Author(s):  
Sebastian Baumann ◽  
Artem Komissarov ◽  
Maria Gili ◽  
Verena Ruprecht ◽  
Stefan Wieser ◽  
...  
Keyword(s):  
Transport System ◽  
Mammalian Cells ◽  
Cell Polarization ◽  
Long Term Memory ◽  
Asymmetric Distribution ◽  
Messenger Rnas ◽  
Mrna Transport ◽  
Transport Efficiency ◽  
Essential Components

Through the asymmetric distribution of messenger RNAs (mRNAs), cells spatially regulate gene expression to create cytoplasmic domains with specialized functions. In neurons, mRNA localization is required for essential processes such as cell polarization, migration, and synaptic plasticity underlying long-term memory formation. The essential components driving cytoplasmic mRNA transport in neurons and mammalian cells are not known. We report the first reconstitution of a mammalian mRNA transport system revealing that the tumor suppressor adenomatous polyposis coli (APC) forms stable complexes with the axonally localized β-actin and β2B-tubulin mRNAs, which are linked to a kinesin-2 via the cargo adaptor KAP3. APC activates kinesin-2, and both proteins are sufficient to drive specific transport of defined mRNA packages. Guanine-rich sequences located in 3′UTRs of axonal mRNAs increase transport efficiency and balance the access of different mRNAs to the transport system. Our findings reveal a minimal set of proteins sufficient to transport mammalian mRNAs.

scholarly journals Fetal Bisphenol-A Induced Changes in Murine Behavior and Brain Gene Expression Persisted in Adult-aged Offspring

Endocrinology ◽  
2020 ◽  
Vol 161 (12) ◽  
Author(s):  
Zhihao Wang ◽  
Myles H Alderman ◽  
Cyrus Asgari ◽  
Hugh S Taylor
Keyword(s):  
Gene Expression ◽  
Locomotor Activity ◽  
Bisphenol A ◽  
In Utero ◽  
Learning Ability ◽  
Long Term Memory ◽  
In Utero Exposure ◽  
Term Memory ◽  
Brain Gene Expression

Abstract In utero Bisphenol A (BPA) exposure has been linked to many deficits during brain development, including sexual differentiation, behavior, and motor coordination. Yet, how BPA induces these disorders and whether its effects are long lasting are largely unknown. In this study, using a mouse model, we demonstrated that in utero exposure to an environmentally relevant dose of BPA induced locomotor deficits, anxiety-like behavior, and declarative memory impairments that persisted into old age (18 months). Compared to the control animals, the BPA-exposed mice had a significant decrease in locomotor activity, exploratory tendencies, and long-term memory, and an increase in anxiety. The global brain gene expression profile was altered permanently by BPA treatment and showed regional and sexual differences. The BPA-treated male mice had more changes in the hippocampus, while female mice experienced more changes in the cortex. Overall, we demonstrate that in utero exposure to BPA induces permanent changes in brain gene expression in a region-specific and sex-specific manner, including a significant decrease in locomotor activity, learning ability, long-term memory, and an increase in anxiety. Fetal/early life exposures permanently affect neurobehavioral functions that deteriorate with age; BPA exposure may compound the effects of aging.

scholarly journals Expression profiles and prognostic significance of WNT family members in glioma via bioinformatic analysis

2020 ◽  
Vol 40 (3) ◽  
Author(s):  
Anqi Xu ◽  
Huiping Yang ◽  
Kunjie Gao ◽  
Zhengming Zhan ◽  
Zibin Song ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Expression Profiles ◽  
Prognostic Significance ◽  
Bioinformatic Analysis ◽  
The Cancer Genome Atlas ◽  
Poor Overall Survival ◽  
Cancer Genome Atlas ◽  
Expression Status ◽  
Genome Atlas

Abstract Aims: The dysregulation and essential role of WNTs in glioma have been widely implicated. However, there is a paucity of literature on the expression status of all the 19 WNTs in glioma. Our study was aimed to evaluate the expression and prognostic values of the 19 WNTs in glioma. Methods: mRNA expression and clinical data were retrieved from the Cancer Genome Atlas (TCGA) database, Chinese Glioma Genome Atlas (CGGA), GTEx and ONCOMINE databases. The 50 frequent neighbor genes of WNT5A and WNT10B were shown with PPI network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Results: We found that the mRNA expression of WNT5A was significantly higher in glioma; however, the WNT10B expression was significantly lower in glioma. Furthermore, the expression of WNT5A and WNT10B was associated with the clinicopathology of glioma. The survival analysis revealed that the higher expressions of WNT5A and WNT16 were associated poor overall survival (OS) in patients with glioma. Conversely, overexpression of WNT3, WNT5B, and WNT10B was associated with better OS. Finally, Go and KEGG analysis revealed WNT5A was associated with multiple signal translations, and crucial oncogenes (EGFR and MDM2) and 2 important tumor suppressors (PTEN and IKN4a/ARF) were found closely correlated with WNT5A in glioma. Conclusion: Among 19WNTs, WNT5A can serve as a candidate to diagnose and therapy glioma, while WNT10B might be valuable for anti-glioma research. The presumed direction was provided to explore the relation of WNTs signal and multiple pathways in glioma.

scholarly journals Why Cytoskeletal Associated Proteins are Important in Colorectal Cancer Patients: Molecular & Bioinformatic Analysis

2021 ◽  
Vol 1 (1) ◽  
pp. 14-31
Author(s):  
Dilara Fatma Akin Bali
Keyword(s):  
Colorectal Cancer ◽  
Mrna Expression ◽  
Expression Profiles ◽  
Point Mutations ◽  
Analysis Data ◽  
Bioinformatic Analysis ◽  
The Cancer Genome Atlas ◽  
Messenger Ribonucleic Acid ◽  
Bioinformatic Tools ◽  
Functional Relations

Introduction: It has been aimed to analyze the role of pathogenic effects of mutation and expression anomalies occurring on diaphanous-related formin 1 (DIAPH1), WASP actin nucleation-promoting factor (WASP), myosin heavy chain 9 (MYH9), actinin alpha 1 (ACNT1), filamin A (FLNA), and tubulin beta 1 class VI (TUBB1), which are known as fundamental cellular skeleton proteins, on the development and progression of cancer via bioinformatic tools. Methods: The genome sequence and expression profiles of 594 Colorectal Cancer (CRC) patients were obtained via bioinformatic tools, which provide data for The Cancer Genome Atlas. The mutation patterns of six genes were determined in detail, and for the prediction of pathogenic properties of identified changes for CRC, Polymorphism Phenotyping v2, Screening for Non-Acceptable Polymorphisms, and the Catalogue Of Somatic Mutations In Can- cer were utilized. Apart from the mutation profile, the effects of existing mutations on messenger ribonucleic acid (mRNA) expression and survival were also identified. Moreover, the Search Tool for the Retrieval of Interacting Genes/Proteins network analysis was realized to further comprehend the functional relations of proteins in cellu- lar processes. Results: There have been 142 distinct point mutations, gene amplification, and deep deletions identified on DIAPH1, WAS, MYH9, ACNT1, FLNA, and TUBB1 genes. ACTN1 and FLNA low mRNA expression levels for DIAPH1 increased, and the mRNA expression level was statistically significant (p<0.05). Prognosis-wise, the effect of mRNA expression on survival in the absence of disease was meaningful for FLNA (p=0.011). Discussion and Conclusion: Bioinformatic analysis data in DIAPH1, WASP, MYH9, ACNT1, FLNA, and TUBB1 genes, which are important in CRC pathogenesis revealed in this study, will be a guide for future laboratory studies.

scholarly journals The earliest stages of second language learning: A behavioral investigation of long-term memory and age

2019 ◽  
Author(s):  
Diana Pili-Moss
Keyword(s):  
Language Learning ◽  
Word Order ◽  
Vocabulary Learning ◽  
Procedural Learning ◽  
Learning Ability ◽  
Long Term Memory ◽  
Grammaticality Judgment ◽  
Declarative Learning

A study with 40 L1 Italian 8-9 year old children and its replication with 36 L1 Italian adults investigated the role of declarative and procedural learning ability in the early stages of language learning.The studies investigated: (1) the extent to which memory-related abilities predicted L2 learning of form-meaning mapping between syntax and thematic interpretation, word order and case marking; and (2) the nature of the acquired L2 knowledge in terms of the implicit/explicit distinction.Deploying a computer game in incidental instruction conditions, the participants were aurally trained in the artificial language BrocantoJ over three sessions. Standardized memory tasks, vocabulary learning ability, and an alternating serial reaction time task provided measures of visual/verbal declarative and procedural learning ability. Language learning was assessed via a measure of comprehension during practice and a grammaticality judgment test.Generalized mixed-effects models fitted to both experimental datasets revealed that, although adults attained higher accuracy levels and were faster learners compared to children, the two groups did not differ qualitatively in what they learned. However, by the end of the experiment, adults displayed higher explicit knowledge of syntactic and semantic regularities. During practice, declarative learning ability predicted accuracy in both groups, but procedural learning ability became an increasingly stronger predictor of L2 comprehension only in children. The role of procedural learning ability emerged again only in the child grammaticality judgment test dataset, where it was a statistically significant predictor of learning of word order. In the practice data declarative learning ability and vocabulary learning ability interacted negatively with procedural learning ability in children, whereas declarative learning ability interacted positively with procedural learning ability in adults. Moreover, the positive interaction in adults only obtained for a subset of practice stimuli, i.e. sentences where the processing of linking between morphosyntax and thematic interpretation was required. Overall, the findings support age-related differences and linguistic target differences in the way abilities related to long-term memory predict language learning.

scholarly journals Divergent roles of astrocytic versus neuronal EAAT2 deficiency on cognition and overlap with aging and Alzheimer’s molecular signatures

2019 ◽  
Vol 116 (43) ◽  
pp. 21800-21811 ◽  
Author(s):  
Abhijeet Sharma ◽  
Syed Faraz Kazim ◽  
Chloe S. Larson ◽  
Aarthi Ramakrishnan ◽  
Jason D. Gray ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cognitive Aging ◽  
Excitatory Amino Acid ◽  
Expression Profiles ◽  
Synaptic Function ◽  
Long Term Memory ◽  
Term Memory ◽  
Spatial Reference ◽  
Age Related

The excitatory amino acid transporter 2 (EAAT2) is the major glutamate transporter in the brain expressed predominantly in astrocytes and at low levels in neurons and axonal terminals. EAAT2 expression is reduced in aging and sporadic Alzheimer’s disease (AD) patients’ brains. The role EAAT2 plays in cognitive aging and its associated mechanisms remains largely unknown. Here, we show that conditional deletion of astrocytic and neuronal EAAT2 results in age-related cognitive deficits. Astrocytic, but not neuronal EAAT2, deletion leads to early deficits in short-term memory and in spatial reference learning and long-term memory. Neuronal EAAT2 loss results in late-onset spatial reference long-term memory deficit. Neuronal EAAT2 deletion leads to dysregulation of the kynurenine pathway, and astrocytic EAAT2 deficiency results in dysfunction of innate and adaptive immune pathways, which correlate with cognitive decline. Astrocytic EAAT2 deficiency also shows transcriptomic overlaps with human aging and AD. Overall, the present study shows that in addition to the widely recognized astrocytic EAAT2, neuronal EAAT2 plays a role in hippocampus-dependent memory. Furthermore, the gene expression profiles associated with astrocytic and neuronal EAAT2 deletion are substantially different, with the former associated with inflammation and synaptic function similar to changes observed in human AD and gene expression changes associated with inflammation similar to the aging human brain.

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