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
-
Does Parkinson’s Disease and Type-2 Diabetes Mellitus Present Common Pathophysiological Mechanisms and Treatments?
CNS & Neurological Disorders - Drug Targets Retromer's Role in Endosomal Trafficking and Impaired Function in Neurodegenerative Diseases
Current Protein & Peptide Science Ibandronate in Benign Bone Disease
Reviews on Recent Clinical Trials Role of Ectonucleotidases in Synapse Formation During Brain Development: Physiological and Pathological Implications
Current Neuropharmacology Patent Selections
Recent Patents on Anti-Infective Drug Discovery Compensating, Controlling, Resigning and Accepting-Older Persons Perception of Physical Decline
Current Aging Science The Proline-Rich Domain and the Microtubule Binding Domain of Protein Tau Acting as RNA Binding Domains
Protein & Peptide Letters Depression in Schizophrenia, Can it be Treated? A Review of the Evidence
Current Psychiatry Reviews Local Cerebral Blood Flow is Preserved in Sepsis
Current Neurovascular Research Other Proteins Involved in Parkinson's Disease and Related Disorders
Current Protein & Peptide Science Regulation of Blood Flow by Prostaglandins
Current Vascular Pharmacology APOE Genotypes and Brain Imaging Classes in Normal Cognition, Mild Cognitive Impairment, and Alzheimer’s Disease: A Longitudinal Study
Current Alzheimer Research Therapeutic Approach of Histamine H3 Receptors in Obesity
Recent Patents on CNS Drug Discovery (Discontinued) Safety and Efficacy of Baclofen in the Treatment of Alcohol-Dependent Patients
Current Pharmaceutical Design Animal Models for the Development of New Neuropharmacological Therapeutics in the Status Epilepticus
Current Neuropharmacology HIV-1 Vectors: Fulfillment of Expectations, Further Advancements, and Still A Way To Go
Current HIV Research Angiogenesis and Hypoxia in Glioblastoma: A Focus on Cancer Stem Cells
CNS & Neurological Disorders - Drug Targets Prescription Opioid Abuse and its Potential Role in Gross Dental Decay
Current Drug Safety Impact of Telaprevir in HCV Patients with Cirrhosis and RVR: Real-Life Data from Boceprevir or Telaprevir based “Triple Therapy” Experience in Southern Italy
Reviews on Recent Clinical Trials The Role of Glioma Microenvironment in Immune Modulation: Potential Targets for Intervention
Letters in Drug Design & Discovery