The Neuroprotective Effect of Neural Cell Adhesion Molecule L1 in the Hippocampus of Aged Alzheimer’s Disease Model Mice

Author:

Aksic Miljana1,Jakovcevski Igor23ORCID,Hamad Mohammad I. K.4ORCID,Jakovljevic Vladimir5ORCID,Stankovic Sanja16ORCID,Vulovic Maja7

Affiliation:

1. Center for Medical Biochemistry, University Clinical Center of Serbia, 11000 Belgrade, Serbia

2. Institut für Anatomie und Klinische Morphologie, Universität Witten/Herdecke, 58455 Witten, Germany

3. Department of Neuroanatomy and Molecular Brain Research, Institute of Anatomy, Ruhr Universität Bochum, 44801 Bochum, Germany

4. Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 64141, United Arab Emirates

5. Center of Excellence for Redox Balance Research, Cardiovascular and Metabolic Disorders, Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia

6. Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia

7. Department of Anatomy, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia

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.

Funder

United Arabic Emirates University

UAEU UPAR

Publisher

MDPI AG

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