scholarly journals Low Sucrose, Omega-3 Enriched Diet Has Region-Specific Effects on Neuroinflammation and Synaptic Function Markers in a Mouse Model of Doxorubicin-Based Chemotherapy

Nutrients ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 2004 ◽  
Author(s):  
Tonya Orchard ◽  
Monica Gaudier-Diaz ◽  
Panchita Phuwamongkolwiwat-Chu ◽  
Rebecca Andridge ◽  
Maryam Lustberg ◽  
...  
Keyword(s):  
Gene Expression ◽  
Brain Regions ◽  
Chemotherapeutic Agents ◽  
Synaptic Function ◽  
Omega 3 ◽  
Brain Functioning ◽  
Specific Effects ◽  
Injection Regimen

Chemotherapeutic agents such as doxorubicin may negatively affect long-term brain functioning in cancer survivors; neuroinflammation may play a causal role. Dietary approaches that reduce inflammation, such as lowering sucrose and increasing eicosapentaenoic acid plus docosahexaenoic acid (EPA + DHA), may attenuate chemotherapy-induced neuroinflammation and synaptic damage, thereby improving quality of life. Ovariectomized, C57BL/6 mice were assigned to a chemotherapy (9 mg/kg doxorubicin + 90 mg/kg cyclophosphamide) or vehicle two-injection regimen, with injections two and four weeks after starting diets. In Study 1, mice received low sucrose diets with EPA + DHA or No EPA + DHA for four to six weeks; tissues were collected four, seven, or 14 days after the second injection. Compared to vehicle, chemotherapy increased pro-inflammatory cytokine IL-1β at day seven in the cortex and hippocampus, and reduced gene expression of synaptic marker Shank 3 at all timepoints in cortex, while EPA + DHA increased expression of Shank 3. In Study 2, high or low sucrose/EPA + DHA or No EPA + DHA diets were fed for five weeks; tissues were collected ten days after the second injection. Among chemotherapy-treated mice, brain DHA was higher with low sucrose feeding. Furthermore, low sucrose increased gene expression of Shank 1, while EPA + DHA increased expression of Shank 3 and reduced protein concentrations of pro-inflammatory markers IL-5, IL-6 and KC/GRO in the cortex, but not the hippocampus. Low sucrose, EPA + DHA diets may attenuate neuroinflammation and synaptic damage induced by doxorubicin-based chemotherapy in specific brain regions.

scholarly journals Transcriptome profiles in brains of mice heterozygous for a DYT1 dystonia-associated mutation in the endogenous Tor1a gene

2019 ◽  
Author(s):  
Sara B. Mitchell ◽  
Michael S. Chimenti ◽  
Hiroyuki Kawano ◽  
Tsun Ming Tom Yuen ◽  
Ashley E. Sjurson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Body Movement ◽  
Gene Expression Profiles ◽  
Brain Regions ◽  
Brain Disorder ◽  
Dyt1 Dystonia ◽  
Differential Gene

ABSTRACTIn patients with the brain disorder dystonia, body movement is severely affected – with involuntary muscle contractions and abnormal postures, causing extensive deterioration of the patient’s quality of life. The most common inherited form of this disorder is DYT1 dystonia, which is caused by a mutation in TOR1A gene and autosomal dominant. The molecular mechanisms that underlie the effects of the TOR1A mutation on brain function remain unclear. To understand these, we examined the gene expression profiles (transcriptome) in four brain regions (cerebral cortex, hippocampus, striatum and cerebellum) in a mouse model, the heterozygous ΔE-torsinA knock-in mice which genetically reproduce the mutation in DYT1 dystonia. The samples were obtained at 2 to 3 weeks of age, a period during which synaptic abnormalities have been reported. Pairwise comparisons of brain regions revealed differential gene expression irrespective of genotype. A comparison of heterozygous to wild-type mice failed to reveal genotype-dependent differences in gene expression in any of the four brain regions when examined individually. However, genotype-dependent differences became apparent when the information for all brain regions was combined. These results suggest that any changes in the transcriptome within a brain region were subtle at this developmental stage, but that statistically significant changes occur across all brain regions. Such changes in the transcriptome, although subtle in degree, could underlie the processes that give rise to DYT1 dystonia.

scholarly journals Epigenetic Regulatory Dynamics in Models of Methamphetamine-Use Disorder

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1614
Author(s):  
Subramaniam Jayanthi ◽  
Michael T. McCoy ◽  
Jean Lud Cadet
Keyword(s):  
Gene Expression ◽  
Brain Regions ◽  
Reward Processing ◽  
Post Translational Modifications ◽  
Methamphetamine Use ◽  
Underlying Mechanisms ◽  
Induced Changes ◽  
Methamphetamine Use Disorder ◽  
Disease Exposure

Methamphetamine (METH)-use disorder (MUD) is a very serious, potentially lethal, biopsychosocial disease. Exposure to METH causes long-term changes to brain regions involved in reward processing and motivation, leading vulnerable individuals to engage in pathological drug-seeking and drug-taking behavior that can remain a lifelong struggle. It is crucial to elucidate underlying mechanisms by which exposure to METH leads to molecular neuroadaptive changes at transcriptional and translational levels. Changes in gene expression are controlled by post-translational modifications via chromatin remodeling. This review article focuses on the brain-region specific combinatorial or distinct epigenetic modifications that lead to METH-induced changes in gene expression.

Roles of CREB Signaling Pathway in Regulation of Fear Memory

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
S. Kida
Keyword(s):  
Gene Expression ◽  
Gene Expression Regulation ◽  
Fear Memory ◽  
Brain Regions ◽  
Contextual Fear ◽  
Contextual Fear Memory ◽  
New Gene ◽  
Activity Dependent

Activity-dependent gene expression through activation of Ca2+-CREB signal transduction pathways has been thought to play a central role in fear memory formation. On the other hand, retrieval of fear memory triggers two time-dependent phases of reactivated memory; reconsolidation and extinction. To understand the mechanisms for determining the fate of the reactivated fear memory, we investigated roles of CREB in reconsolidation and extinction of contextual fear memory and then analyzed the brain-regions regulating reconsolidation and extinction by identifying regions where CREB-mediated gene expression is activated and then examining the role of protein synthesis in those regions on reconsolidation and extinction. We first showed that activation of CREB-mediated transcription is required for reconsolidation and long-term extinction of contextual fear memory. Using immunocytochemical analyses, we demonstrated that CREB is activated in the hippocampus/amygdala and amygdala/medial prefrontal cortex (mPFC) in the reconsolidation and extinction phases, respectively. Similar results were observed by analyzing the expression of a CREB-dependent gene, Arc. We finally showed that reconsolidation and long-term extinction of the contextual fear memory depended on new gene expression in the hippocampus/amygdala and amygdala/mPFC, respectively. Thus reactivated contextual fear memory is reconsolidated or extinguished through distinct CREB-mediated gene expression regulation in the hippocampus, amygdala and mPFC.

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.

scholarly journals Establishment and quality evaluation of a glioma biobank in Beijing Tiantan Hospital

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4450 ◽  
Author(s):  
Fanhong Kong ◽  
Wenli Zhang ◽  
Lin Qiao ◽  
Qi Li ◽  
Haowen Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Quality Evaluation ◽  
Housekeeping Gene ◽  
Storage Conditions ◽  
Dna Integrity ◽  
Morphological Examination ◽  
Rna Integrity ◽  
Standard Operating

Background We established a glioma biobank at Beijing Tiantan Hospital in November, 2010. Specialized residents have been trained to collect, store and manage the biobank in accordance with standard operating procedures. Methods One hundred samples were selected to evaluate the quality of glioma samples stored in the liquid nitrogen tank during different periods (from 2011 to 2015) by morphological examination, RNA integrity determination, DNA integrity determination and housekeeping gene expression determination. Results The majority of samples (95%) had high RNA quality for further analysis with RIN ≥6. Quality of DNA of all samples were stable without significant degradation. Conclusion Storage conditions of our biobank are suitable for long-term (at least five years) sample preservation with high molecular quality.

Omega-3 fatty acids partially revert the metabolic gene expression profile induced by long-term calorie restriction

2016 ◽  
Vol 77 ◽  
pp. 29-37 ◽  
Author(s):  
José Alberto López-Domínguez ◽  
Ángela Cánovas ◽  
Juan F. Medrano ◽  
Alma Islas-Trejo ◽  
Kyoungmi Kim ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acids ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Calorie Restriction ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Metabolic Gene ◽  
Metabolic Gene Expression

scholarly journals Maternal stress has divergent effects on gene expression patterns in the brains of male and female threespine stickleback

2016 ◽  
Vol 283 (1839) ◽  
pp. 20161734 ◽  
Author(s):  
David C. H. Metzger ◽  
Patricia M. Schulte
Keyword(s):  
Gene Expression ◽  
Maternal Stress ◽  
Expression Patterns ◽  
Protein Translation ◽  
Threespine Stickleback ◽  
Synaptic Function ◽  
Male And Female ◽  
Brain Transcriptome ◽  
The Brain

Maternal stress can have long-term effects on neurodevelopment that can influence offspring performance and population evolutionary trajectories. To examine the mechanistic basis for these neurodevelopmental effects of maternal stress, we used RNA-seq to assess differential gene expression across the brain transcriptome of adult male and female threespine stickleback ( Gasterosteus aculeatus ) from stressed and unstressed mothers. We identified sexually divergent effects of maternal stress on the brain transcriptome. In males, genes that were upregulated by maternal stress were enriched for processes involved in synaptic function and organization and steroid hormone-mediated signalling pathways, whereas in females genes that were upregulated by maternal stress were enriched for processes involved in protein translation and metabolic functions. The expression of several genes involved in the hypothalamic–pituitary–interrenal response to stress and epigenetic processes such as the regulation of DNA methylation patterns and miRNAs increased in males and not in females. These data suggest that maternal stress has markedly different effects on cellular pathways in the brains of male and female offspring of mothers that are exposed to stress, which could have important implications when assessing the long-term ecological and evolutionary impacts of stress across generations.

Quality of early-life maternal care predicts empathy-like behavior in adult male rats: linking empathy to BDNF gene expression in associated brain regions

2021 ◽  
pp. 147568
Author(s):  
Ehsan Asadi ◽  
Fariba Khodagholi ◽  
Sareh Asadi ◽  
Hamed Mohammadi Kamsorkh ◽  
Neda Kaveh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adult Male ◽  
Maternal Care ◽  
Early Life ◽  
Brain Regions ◽  
Male Rats ◽  
Bdnf Gene

Thinking Beyond Language: Intervention for Severe Aphasia

2009 ◽  
Vol 19 (1) ◽  
pp. 15-22 ◽  
Author(s):  
Nina Simmons-Mackie
Keyword(s):  
Quality Of Life ◽  
Communication Training ◽  
Language Intervention ◽  
Specific Training ◽  
Environmental Support ◽  
Total Communication ◽  
Communication Partners

Abstract Purpose: This article addresses several intervention approaches that aim to improve life for individuals with severe aphasia. Because severe aphasia significantly compromises language, often for the long term, recommended approaches focus on additional domains that affect quality of life. Treatments are discussed that involve increasing participation in personally relevant life situations, enhancing environmental support for communication and participation, and improving communicative confidence. Methods: Interventions that have been suggested in the aphasia literature as particularly appropriate for people with severe aphasia include training in total communication, training of communication partners, and activity specific training. Conclusion: Several intervention approaches can be implemented to enhance life with severe aphasia.

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