Research Paper Volume 11, Issue 17 pp 7257—7273
Genomic deletion of TLR2 induces aggravated white matter damage and deteriorated neurobehavioral functions in mouse models of Alzheimer’s disease
- 1 Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
- 2 Institute of Neurological Diseases, Xuzhou Medical University, Xuzhou, China
- 3 Department of Neurology, Xuzhou Central Hospital, Xuzhou, China
- 4 Augusta University/University of Georgia Medical Partnership, Athens, GA 30606, USA
- 5 Medical College of Georgia, Augusta University, Augusta, GA 30606, USA
received: February 25, 2019 ; accepted: September 2, 2019 ; published: September 11, 2019 ;https://doi.org/10.18632/aging.102260
How to Cite
Copyright © 2019 Zhou et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Toll-like receptor-2 (TLR2), a member of the TLR family, plays an important role in the initiation and regulation of immune/inflammation response, which is a critical mechanism underlying Alzheimer’s disease (AD). To clarify the role of TLR2 in the pathological process of AD, in the present study, TLR2 knockout plus APPswe/PSEN1dE9 transgenic mice (AD-TLR2KO) were generated. Neurobehavioral tests and brain MRI scan were conducted on mice at the age of 12 months. Additionally, neuron loss was evaluated using NeuN staining. Amyloid β protein (Aβ), glial fibrillary acidic protein (GFAP), endogenous ligands for TLR2, and the activation of downstream signaling of TLR2 in mouse brains were detected by immunohistochemistry and Western blots. The results demonstrated that TLR2 deficit induced learning disabilities, decreased spontaneous activity, increased anxiety and depression, and led to white matter damage (WMD), brain atrophy, loss of neurons, and glial activation. Moreover, TLR2 deficit aggravated impaired neurobehavioral functions and WMD in AD mice, but did not affect the Aβ deposition in mouse brains. Our data indicate that the genomic deletion of TLR2 impairs neurobehavioral functions, induces WMD and brain atrophy, and increases the activation of astrocytes, which in turn aggravate the symptoms of AD through a non-Aβ mechanism.