Abstract
Background: It is well known that alterations in astrocytes occur in Alzheimer’s disease and reactive astrogliosis is one of the hallmarks of the disease. Recently, data has emerged that suggests that alterations in astrocytes may also occur early in the pathogenesis of the disease.
Objective: The aim of present work was to characterize the transcriptional alterations occurring in cultured astrocytes from 3xTg-AD mouse pups compared to control non-transgenic mice. Furthermore, we also compared these changes to those reported by others in astrocytes from symptomatic AD mice.
Method: We conducted a whole-genome microarray study on primary cultured astrocytes from the hippocampus of 3xTg-AD and non-transgenic mouse newborn pups. We used cross-platform normalization and an unsupervised hierarchical clustering algorithm to compare our results with other datasets of cultured or freshly isolated astrocytes, including those isolated from plaque-stage APPswe/PS1dE9 AD mice.
Results: We found a set of 993 genes differentially expressed in 3xTg-AD as compared with non-Tg astrocytes. Over-represented gene ontology terms were related to calcium, cell-cell communication, mitochondria, transcription, nucleotide binding and phosphorylation. Of note, no genes related to inflammation were found in cultured 3xTg-AD astrocytes. Comparison with astrocytes isolated from plaque stage APPswe/PS1dE9 showed that 882 out of 993 genes were selectively changed in primary 3xTg-AD astrocytes while 50 genes were co-regulated and 61 were anti-regulated (regulated in the opposite direction in the datasets).
Conclusion: Our data show that in cultured astrocytes from an AD mouse model, transcriptional changes occur and are different from those reported in models mimicking later stages of the disease.
Keywords: Whole-genome microarray, 3xTg-AD mice, cultured astroglia, cross-platform normalization, early Alzheimer`s disease, FAD mutations.
Current Alzheimer Research
Title:Transcriptional Remodeling in Primary Hippocampal Astrocytes from an Alzheimer’s Disease Mouse Model
Volume: 15 Issue: 11
Author(s): F. Ruffinatti, L. Tapella, I. Gregnanin, A. Stevano, G. Chiorino, P.L. Canonico, C. Distasi, A.A. Genazzani*D. Lim*
Affiliation:
- Department of Pharmaceutical Sciences, Universita del Piemonte Orientale, Via Bovio 6, 28100, Novara,Italy
- Department of Pharmaceutical Sciences, Universita del Piemonte Orientale, Via Bovio 6, 28100, Novara,Italy
Keywords: Whole-genome microarray, 3xTg-AD mice, cultured astroglia, cross-platform normalization, early Alzheimer`s disease, FAD mutations.
Abstract: Background: It is well known that alterations in astrocytes occur in Alzheimer’s disease and reactive astrogliosis is one of the hallmarks of the disease. Recently, data has emerged that suggests that alterations in astrocytes may also occur early in the pathogenesis of the disease.
Objective: The aim of present work was to characterize the transcriptional alterations occurring in cultured astrocytes from 3xTg-AD mouse pups compared to control non-transgenic mice. Furthermore, we also compared these changes to those reported by others in astrocytes from symptomatic AD mice.
Method: We conducted a whole-genome microarray study on primary cultured astrocytes from the hippocampus of 3xTg-AD and non-transgenic mouse newborn pups. We used cross-platform normalization and an unsupervised hierarchical clustering algorithm to compare our results with other datasets of cultured or freshly isolated astrocytes, including those isolated from plaque-stage APPswe/PS1dE9 AD mice.
Results: We found a set of 993 genes differentially expressed in 3xTg-AD as compared with non-Tg astrocytes. Over-represented gene ontology terms were related to calcium, cell-cell communication, mitochondria, transcription, nucleotide binding and phosphorylation. Of note, no genes related to inflammation were found in cultured 3xTg-AD astrocytes. Comparison with astrocytes isolated from plaque stage APPswe/PS1dE9 showed that 882 out of 993 genes were selectively changed in primary 3xTg-AD astrocytes while 50 genes were co-regulated and 61 were anti-regulated (regulated in the opposite direction in the datasets).
Conclusion: Our data show that in cultured astrocytes from an AD mouse model, transcriptional changes occur and are different from those reported in models mimicking later stages of the disease.
Export Options
About this article
Cite this article as:
Ruffinatti F., Tapella L., Gregnanin I., Stevano A., Chiorino G., Canonico P.L., Distasi C., Genazzani A.A.*, Lim D.*, Transcriptional Remodeling in Primary Hippocampal Astrocytes from an Alzheimer’s Disease Mouse Model, Current Alzheimer Research 2018; 15 (11) . https://dx.doi.org/10.2174/1567205015666180613113924
DOI https://dx.doi.org/10.2174/1567205015666180613113924 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
Diagnostic and therapeutic biomarkers of dementia
Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Cytokines as Regulators of Atherosclerosis in Murine Models
Current Drug Targets Screening Neuroprotective Agents Through 4-hydroxynonenal, Ethanol, High Glucose, Homocysteine, Okadaic Acid, Rotenone, and Oxygen-Glucose Deprivation Induced PC12 Injury Models: A Review
Current Psychopharmacology Preterm Infant Swallowing and Respiration Coordination During Oral Feeding: Relationship to Dysphagia and Aspiration
Current Pediatric Reviews Nose-to-brain Delivery of Natural Compounds for the Treatment of Central Nervous System Disorders
Current Pharmaceutical Design Modulation of Alzheimers Amyloidosis by Statins: Mechanisms of Action
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Transcription Factors in Autoimmune Diseases
Current Pharmaceutical Design The Current Status and Future Perspectives of Studies of Cannabinoid Receptor 1 Antagonists as Anti-Obesity Agents
Current Topics in Medicinal Chemistry An Optimal Combination of Chemically Pure Compounds from <i>Salvia miltiorrhiza</i> for Inhibiting Cell Proliferation
Cardiovascular & Hematological Agents in Medicinal Chemistry Editorial [Hot Topic: Comparative Biochemistry of Molecular Targets for Drug and Pesticides: N-Acetyl-D-glucosamine and Acetylcholine Related Enzymes (Guest Editor: Qing Yang )]
Current Drug Targets Long-Term Follow-Up of Patients Immunized with AN1792: Reduced Functional Decline in Antibody Responders
Current Alzheimer Research Towards a Causal Model for Disgust in the Anxiety Disorders: An Integration of Evidence from Neuroscience
Current Psychiatry Reviews Population Diversity and its Relationship with Infectious and Tumor Diseases
Current Immunology Reviews (Discontinued) Selective Inhibition of SIRT2 Improves Outcomes in a Lethal Septic Model
Current Molecular Medicine Current Trends and Future Strategies for the Global Impact of COVID-19 Pandemic
Coronaviruses Capsaicin-Sensitive Nociceptive Innervation of the Dura Mater: Implications for the Pathomechanism of Headache
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Analgesia and Sedation in Mechanical Ventilation in Neonatology
Current Respiratory Medicine Reviews Nutritional and Therapeutic Potential of Garlic and Onion (Allium sp.)
Current Nutrition & Food Science Synthesis and In Vivo Antimalarial Evaluation of Novel Hydroxyethylamine Derivatives
Medicinal Chemistry The Heart and Brain Imaging in Lone Atrial Fibrillation – Are We Surprised?
Current Pharmaceutical Design Preface [Hot Topic: Molecular and Cellular Mechanisms of Ischemic Cell Death in the Brain (Executive Editor: Rita Sattler)]
Current Molecular Medicine