Neural stem cell transplantation decreases neuroinflammation in a transgenic mouse model of Alzheimer's disease

Qi Zhang; Hua-Hui Wu; Yuan Wang; Guo-Jun Gu; Wei Zhang; Rong Xia

doi:10.1111/jnc.13413

Neural stem cell transplantation decreases neuroinflammation in a transgenic mouse model of Alzheimer's disease

J Neurochem. 2016 Feb;136(4):815-825. doi: 10.1111/jnc.13413. Epub 2015 Dec 28.

Authors

Qi Zhang¹, Hua-Hui Wu², Yuan Wang¹, Guo-Jun Gu³, Wei Zhang⁴, Rong Xia¹

Affiliations

¹ Department of Blood Transfusion, Huashan Hospital, Fudan University, Shanghai, China.
² Harbin Hospital of Traditional Chinese Medicine, Harbin, Heilongjiang, China.
³ Department of Medical Imaging, Tongji Hospital, Medical School of Tongji University, Shanghai, China.
⁴ Department of Medical Imaging, Renji Hospital, Medical School of Jiaotong University, Shanghai, China.

PMID: 26525612
DOI: 10.1111/jnc.13413

Abstract

Inflammatory processes are considered to play an important role in the progression of neurodegenerative changes in Alzheimer's disease (AD). A number of studies have reported that inflammatory processes are highly correlated with cognitive deficits in AD-like mice. Transplantation of neural stem cells (NSCs) has been considered as a potential new therapy for the treatment of AD because of its effects in improving cognitive ability. However, NSCs have not been evaluated for their protective effects against inflammatory changes in AD. Here, we injected NSCs into amyloid precursor protein (APP)/PS1 transgenic mice to analyse cognitive function and to measure glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor molecule-1 (Iba-1) and toll-like receptors 4(TLR4) activation. We also quantified TLR-4 pathway-related agents, Aβ concentration and the levels of proinflammatory mediators. Our results showed that in NSC-injected APP/PS1 mice, activation of GFAP, Iba-1, TLR4 and TLR4 pathway-related agents (MyD88, TRIF, P38 MAPK and NF-κB P65) were significantly decreased with decreased expression of proinflammatory mediators (IL-1, IL-6, TNF-α and PGE2). These changes were associated with the amelioration of cognitive deficits, but no difference was found in Aβ concentration. Our results provide novel evidence that NSC transplantation in APP/PS1 mice significantly improved cognitive deficits and was accompanied by the attenuation of inflammatory injury via suppression of glial and TLR4-mediated inflammatory pathway activation. Our data indicate that these pathways may potentially be important therapeutic targets to prevent or delay AD. This study investigated the neuroprotective effect of neural stem cell (NSC) transplantation against Alzheimer's disease (AD) inflammation. We found that NSC treatment in APP/PS1 mice significantly improved cognitive deficits and was accompanied by the attenuation of inflammatory injury via suppression of glial and toll-like receptor 4 (TLR4) activation and its downstream signalling pathways. Our findings indicate that these pathways may be potentially important therapeutic targets to prevent or delay AD.

Keywords: Alzheimer's disease; TLR4; astrocyte; microglia; neural stem cells; neuroinflammation.