Levodopa ameliorates learning and memory deficits in a murine model of Alzheimer’s disease
Abstract
Dopamine plays an important role in learning and memory processes. A deficit of this neurotransmitter as it is apparent in Alzheimer's disease (AD) may contribute to cognitive decline, a major symptom of AD patients. The aim of this study was to elucidate whether or not stimulation of the dopaminergic system leads to an improvement of cognitive function and reduction of non-cognitive behavioral alterations in a murine model of AD. Transgenic and wild type male mice of the TgCRND8 line were treated either with the dopamine precursor levodopa or vehicle and tested in two learning tasks, the object-recognition task and the Barnes maze test. Additionally 24 h spontaneous behavior in the home cage was analyzed. In both memory tasks wild type mice performed significantly better than transgenics. However, transgenics treated with levodopa showed a significant object recognition memory and improved acquisition of spatial memory in the Barnes maze compared to vehicle treated transgenics. Concerning spontaneous behavior transgenic mice performed much more stereotypies than wild types. However, there was a trend for reduced stereotypies in the levodopa group in the time the drug was active. Neurochemical analysis revealed elevated levels of dopamine in the neostriata and frontal cortices and reduced levels in the hippocampi of transgenic mice compared to wild types. Thus cognitive deficits and stereotypies may be due to changes in the dopaminergic system as they could be ameliorated by levodopa treatment, that might also have a therapeutic significance for AD.
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The increase of DA drive, evoked by dopaminergic drugs or stimulation of dopaminergic neurotransmission, improves synaptic plasticity dysfunctions, cognitive impairment and memory deficits in different experimental models of AD.
“the increase of DA drive -evoked by dopaminergic drugs or stimulation of the dopa minergic neurotransmission -improves synaptic plasticity dysfunctions, cognitive impairment and memory deficits in different experimental models of AD”
From Nilotinib restores memory function by preventing dopaminergic neuron degeneration in a mouse model of Alzheimer’s Disease (2021) · cites this paper as Ambrée et al., 2009
TgCRND8 develop deficits in both recognition memory and fear conditioning similar to the temporal time course of spatial working memory and reference memory deficits.
“Similar to this observed temporal time course of spatial working memory and reference memory deficits are the development of deficits in both recognition memory and fear conditioning (Gortz et al., 2008; Richter et al., 2008; Ambree et al., 2009; Hanna et al., 2012).”
From Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models (2014) · cites this paper as Ambree et al., 2009
TgCRND8 reference memory deficits via Barnes maze testing are present at 3 months of age.
“Reference memory deficits via Barnes maze testing are also present at 3 months of age (Gortz et al., 2008; Richter et al., 2008; Ambree et al., 2009).”
From Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models (2014) · cites this paper as Ambree et al., 2009
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- Authors
- Ambrée, O., Richter, H., Sachser, N., Lewejohann, L., Dere, E., de Souza Silva, M. A., Herring, A., Keyvani, K., Paulus, W., & Schäbitz, W.-R.
- Affiliations
- University of Münster (DE)
- Heinrich Heine University Düsseldorf (DE)
- University Hospital Münster (DE)
- Corresponding author
- Ambrée, Oliver
- Schäbitz, Wolf-Rüdiger
- ORCID
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2009-08
- Volume
- 30
- Issue
- 8
- Pages
- 1192-1204
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W1970084030
- Cited by
- 115
- References
- 93
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 9 · 2023: 7 · 2022: 10 · 2021: 9 · 2020: 10 · 2019: 6 · 2018: 10 · 2017: 5 · 2016: 11 · 2015: 3 · 2014: 4 · 2013: 4 · 2012: 3
- FWCI
- 2.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bundesministerium für Bildung und Forschung (01GW0520)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Keywords
- levodopa, Alzheimer's disease, dopaminergic system, learning and memory impairment, object recognition memory, spatial memory, stereotypy, TgCRND8 mice, dopamine levels, hippocampus, neostriatum, frontal cortex, cognitive decline
- MeSH terms
- Alzheimer Disease, Analysis of Variance, Animals, Corpus Striatum, Disease Models, Animal, Dopamine, Frontal Lobe, Hippocampus, Learning Disabilities, Levodopa, Male, Memory Disorders, Mice, Transgenic, Dopamine Agents, Amyloid beta-Peptides, Nootropic Agents, Maze Learning, Recognition, Psychology, Mice
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