Abstract
The cholinergic hypothesis of Alzheimers Disease (AD) has led to a number of animal models to study in vivo the pathogeny of cortical cholinergic involution. The lesion of the cholinergic neurons of the basal forebrain, especially of the nucleus basalis magnocellularis (nbm) of rodents, has been the most utilized method for obtaining these models. Toxic substances such as quinolic, kainic, NMDA, ibotenic and quisqualic acids, the specific cholinergic toxin AF64, amyloid, and antibodies to neurotrophic factors; etc, have been used to produce such lesions. These investigations have helped our understanding of the role of cerebral cholinergic innervation in cognitive disorders and their treatments. However, this research has provided conflicting results, and much controversy has developed surrounding the role of the cholinergic systems and the suitability of these models. It is very important to take into account the exact type of nbm / cortical lesion produced, and its evolution, if meaningful results are to be obtained. This review covers the theoretical and practical use of nbm lesion models, and examines the main positive and negative results obtained by different authors in the light of our own observations on the long-term (3 years) morphological and biochemical changes that occur in several kinds of nbmlesion model rats. The changes seen were very different, but many of them were increased up to the end of life with no clear relationship with the development of the original lesion.
Keywords: alzheimer disease (ad), ad animal models, nucleus basalis, basal forebrain, cortical cholinergic innervation, excitotoxins, ad treatments
Current Alzheimer Research
Title: Lesions and Dysfunctions of the Nucleus Basalis as Alzheimers Disease Models: General and Critical Overview and Analysis of the Long-Term Changes in Several Excitotoxic Models
Volume: 1 Issue: 3
Author(s): A. Toledano and M I. Alvarez
Affiliation:
Keywords: alzheimer disease (ad), ad animal models, nucleus basalis, basal forebrain, cortical cholinergic innervation, excitotoxins, ad treatments
Abstract: The cholinergic hypothesis of Alzheimers Disease (AD) has led to a number of animal models to study in vivo the pathogeny of cortical cholinergic involution. The lesion of the cholinergic neurons of the basal forebrain, especially of the nucleus basalis magnocellularis (nbm) of rodents, has been the most utilized method for obtaining these models. Toxic substances such as quinolic, kainic, NMDA, ibotenic and quisqualic acids, the specific cholinergic toxin AF64, amyloid, and antibodies to neurotrophic factors; etc, have been used to produce such lesions. These investigations have helped our understanding of the role of cerebral cholinergic innervation in cognitive disorders and their treatments. However, this research has provided conflicting results, and much controversy has developed surrounding the role of the cholinergic systems and the suitability of these models. It is very important to take into account the exact type of nbm / cortical lesion produced, and its evolution, if meaningful results are to be obtained. This review covers the theoretical and practical use of nbm lesion models, and examines the main positive and negative results obtained by different authors in the light of our own observations on the long-term (3 years) morphological and biochemical changes that occur in several kinds of nbmlesion model rats. The changes seen were very different, but many of them were increased up to the end of life with no clear relationship with the development of the original lesion.
Export Options
About this article
Cite this article as:
Toledano A. and Alvarez I. M, Lesions and Dysfunctions of the Nucleus Basalis as Alzheimers Disease Models: General and Critical Overview and Analysis of the Long-Term Changes in Several Excitotoxic Models, Current Alzheimer Research 2004; 1 (3) . https://dx.doi.org/10.2174/1567205043332117
DOI https://dx.doi.org/10.2174/1567205043332117 |
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
-
Intraventricular Recombinant Tissue Plasminogen Activator in Treatment of Aneurysmal Intraventricular Hemorrhage: A Meta-Analysis
Current Drug Targets Cerebrovascular Profile Assessment in Parkinson's Disease Patients
CNS & Neurological Disorders - Drug Targets Suicide Gene Therapy Mediated by the Herpes Simplex Virus Thymidine Kinase Gene / Ganciclovir System: Fifteen Years of Application
Current Gene Therapy Conference Report (The XVth International Symposium of Brain Edema and Cellular Injury)
CNS & Neurological Disorders - Drug Targets Aquaporin and Blood Brain Barrier
Current Neuropharmacology Importance of Aquaporins in the Physiopathology of Brain Edema
Current Pharmaceutical Design Transport Mechanisms at the Blood-Cerebrospinal-Fluid Barrier: Role of Megalin (LRP2)
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Recent Development in Neuronal Migration Disorders: Clinical, Neuroradiologic and Genetics Aspects
Current Pediatric Reviews Early Cerebral Infarction Following Aneurysmal Subarachnoid Hemorrhage: Frequency, Risk Factors, Patterns, and Prognosis
Current Neurovascular Research Papillary Tumor of the Pineal Region with Parinaud Syndrome: A Case Report
Current Medical Imaging Novel Agents in CNS Myeloma Treatment
Central Nervous System Agents in Medicinal Chemistry Iron Overload is Associated with Perihematoma Edema Growth Following Intracerebral Hemorrhage that may Contribute to In-hospital Mortality and Long-term Functional Outcome
Current Neurovascular Research Neonatal Ultrasound in Transport
Current Pediatric Reviews Leptomeningeal Metastasis: Challenges in Diagnosis and Treatment
Current Cancer Therapy Reviews The Ultimate Outlier: Transitional Care for Persons with Dementia and BPSD
Current Alzheimer Research Systemic Oxidative Stress in Older Patients with Mild Cognitive Impairment or Late Onset Alzheimer's Disease
Current Alzheimer Research Application of NMR to the Study of Cells and Body Fluids
Current Organic Chemistry Microbial Immune Evasion Employing Suppressor of Cytokine Signaling (SOCS) Proteins
Inflammation & Allergy - Drug Targets (Discontinued) Tuberculosis Infections of the Central Nervous System
Central Nervous System Agents in Medicinal Chemistry Gut Permeability and Microbiota in Parkinson’s Disease: Role of Depression, Tryptophan Catabolites, Oxidative and Nitrosative Stress and Melatonergic Pathways
Current Pharmaceutical Design