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- Title
The Neuroprotective Effect of Neural Cell Adhesion Molecule L1 in the Hippocampus of Aged Alzheimer's Disease Model Mice.
- Authors
Aksic, Miljana; Jakovcevski, Igor; Hamad, Mohammad I. K.; Jakovljevic, Vladimir; Stankovic, Sanja; Vulovic, Maja
- Abstract
Alzheimer's disease (AD) is a severe neurodegenerative disorder and the most common form of dementia, causing the loss of cognitive function. Our previous study has shown, using a doubly mutated mouse model of AD (APP/PS1), that the neural adhesion molecule L1 directly binds amyloid peptides and decreases plaque load and gliosis when injected as an adeno-associated virus construct (AAV-L1) into APP/PS1 mice. In this study, we microinjected AAV-L1, using a Hamilton syringe, directly into the 3-month-old APP/PS1 mouse hippocampus and waited for a year until significant neurodegeneration developed. We stereologically counted the principal neurons and parvalbumin-positive interneurons in the hippocampus, estimated the density of inhibitory synapses around principal cells, and compared the AAV-L1 injection models with control injections of green fluorescent protein (AAV-GFP) and the wild-type hippocampus. Our results show that there is a significant loss of granule cells in the dentate gyrus of the APP/PS1 mice, which was improved by AAV-L1 injection, compared with the AAV-GFP controls (p < 0.05). There is also a generalized loss of parvalbumin-positive interneurons in the hippocampus of APP/PS1 mice, which is ameliorated by AAV-L1 injection, compared with the AAV-GFP controls (p < 0.05). Additionally, AAV-L1 injection promotes the survival of inhibitory synapses around the principal cells compared with AAV-GFP controls in all three hippocampal subfields (p < 0.01). Our results indicate that L1 promotes neuronal survival and protects the synapses in an AD mouse model, which could have therapeutic implications.
- Subjects
NEURAL cell adhesion molecule; GRANULE cells; GREEN fluorescent protein; DENTATE gyrus; ALZHEIMER'S disease
- Publication
Biomedicines, 2024, Vol 12, Issue 8, p1726
- ISSN
2227-9059
- Publication type
Article
- DOI
10.3390/biomedicines12081726