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Elevation of brain magnesium prevents synaptic loss and reverses cognitive deficits in Alzheimer’s disease mouse model
- Source :
- Molecular Brain
- Publisher :
- Springer Nature
-
Abstract
- Background Profound synapse loss is one of the major pathological hallmarks associated with Alzheimer’s disease, which might underlie memory impairment. Our previous work demonstrates that magnesium ion is a critical factor in controlling synapse density/plasticity. Here, we tested whether elevation of brain magnesium, using a recently developed compound (magnesium-L-threonate, MgT), can ameliorate the AD-like pathologies and cognitive deficits in the APPswe/PS1dE9 mice, a transgenic mouse model of Alzheimer’s disease. Results MgT treatment reduced Aβ-plaque, prevented synapse loss and memory decline in the transgenic mice. Strikingly, MgT treatment was effective even when the treatment was given to the mice at the end-stage of their Alzheimer’s disease-like pathological progression. To explore how elevation of brain magnesium ameliorates the AD-like pathologies in the brain of transgenic mice, we studied molecules critical for APP metabolism and signaling pathways implicated in synaptic plasticity/density. In the transgenic mice, the NMDAR signaling pathway was downregulated, while the BACE1 expression were upregulated. MgT treatment prevented the impairment of these signaling pathways, stabilized BACE1 expression and reduced sAPPβ and β-CTF in the transgenic mice. At the molecular level, elevation of extracellular magnesium prevented the high Aβ-induced reductions in synaptic NMDARs by preventing calcineurin overactivation in hippocampal slices. Conclusions Our results suggest that elevation of brain magnesium exerts substantial synaptoprotective effects in a mouse model of Alzheimer’s disease, and hence it might have therapeutic potential for treating Alzheimer’s disease. Electronic supplementary material The online version of this article (doi:10.1186/s13041-014-0065-y) contains supplementary material, which is available to authorized users.
- Subjects :
- Genetically modified mouse
Male
Aging
Transgene
Hippocampus
Down-Regulation
Mice, Transgenic
Plaque, Amyloid
Motor Activity
Receptors, N-Methyl-D-Aspartate
Synaptic Transmission
Brain magnesium
Synapse
Synaptoprotection
Cellular and Molecular Neuroscience
Alzheimer Disease
NMDAR signaling
Medicine
Animals
Aspartic Acid Endopeptidases
Humans
Learning
Magnesium ion
Molecular Biology
Analysis of Variance
Memory Disorders
Amyloid beta-Peptides
business.industry
Research
Body Weight
Brain
BACE1
medicine.disease
Butyrates
Disease Models, Animal
Synaptic plasticity
Synapses
NMDA receptor
Female
Alzheimer's disease
Amyloid Precursor Protein Secretases
business
Cognition Disorders
Neuroscience
Alzheimer’s disease
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 17566606
- Volume :
- 7
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Molecular Brain
- Accession number :
- edsair.doi.dedup.....26f3f4c3a213a50b4ec8712fc8654f2c
- Full Text :
- https://doi.org/10.1186/s13041-014-0065-y