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Therapeutic treatment with the anti-inflammatory drug candidate MW151 may partially reduce memory impairment and normalizes hippocampal metabolic markers in a mouse model of comorbid amyloid and vascular pathology
- Source :
- PLoS ONE, Vol 17, Iss 1, p e0262474 (2022), PLoS ONE, Vol 17, Iss 1 (2022), PLoS ONE
- Publication Year :
- 2022
- Publisher :
- Public Library of Science (PLoS), 2022.
-
Abstract
- Alzheimer’s disease (AD) is the leading cause of dementia in the elderly, but therapeutic options are lacking. Despite long being able to effectively treat the ill-effects of pathology present in various rodent models of AD, translation of these strategies to the clinic has so far been disappointing. One potential contributor to this situation is the fact that the vast majority of AD patients have other dementia-contributing comorbid pathologies, the most common of which are vascular in nature. This situation is modeled relatively infrequently in basic AD research, and almost never in preclinical studies. As part of our efforts to develop small molecule, anti-inflammatory therapeutics for neurological injury and disease, we have recently been exploring potentially promising treatments in preclinical multi-morbidity contexts. In the present study, we generated a mouse model of mixed amyloid and hyperhomocysteinemia (HHcy) pathology in which to test the efficacy of one of our anti-inflammatory compounds, MW151. HHcy can cause cerebrovascular damage and is an independent risk factor for both AD dementia and vascular contributions to cognitive impairment and dementia. We found that MW151 was able to partially rescue hippocampal-dependent spatial memory and learning deficits in this comorbidity context, and further, that the benefit is associated with a normalization of hippocampal metabolites detectable via magnetic resonance spectroscopy. These findings provide evidence that MW151 in particular, and potentially anti-inflammatory treatment more generally, may be beneficial in AD patients with comorbid vascular pathology.
- Subjects :
- Physiology
Anti-Inflammatory Agents
Social Sciences
Alzheimer's Disease
Hippocampus
Diagnostic Radiology
Mice
Medical Conditions
Immune Physiology
Medicine and Health Sciences
Psychology
Mammals
Innate Immune System
Multidisciplinary
Behavior, Animal
Animal Behavior
Radiology and Imaging
Brain
Eukaryota
Neurodegenerative Diseases
Animal Models
Magnetic Resonance Imaging
Neurology
Experimental Organism Systems
Vertebrates
Cytokines
Medicine
Anatomy
Research Article
Imaging Techniques
Science
Immunology
Mouse Models
Research and Analysis Methods
Rodents
Model Organisms
Memory
Diagnostic Medicine
Mental Health and Psychiatry
mental disorders
Animals
Maze Learning
Nutrition
Memory Disorders
Behavior
Organisms
Biology and Life Sciences
Collective Animal Behavior
Molecular Development
Diet
Disease Models, Animal
Immune System
Amniotes
Animal Studies
Dementia
Zoology
Developmental Biology
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 17
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....c93d3f216982757c755b56b9fae2058a