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Front. Aging Neurosci. | doi: 10.3389/fnagi.2019.00124

Decreased netrin-1 and correlated Th17/Tregs balance disorder in Aβ1-42 induced Alzheimer’s disease model rats

 Lina Sun1, Ting Ju1, Tianhang Wang1, Liang Zhang1, Feifan Ding1, Yan Zhang1, Ran An1, Yilei Xun1, You Li1, Yidan Lu1, Xin Zhang1 and  Lijun Chi1*
  • 1Department of Neurology, The First Affiliated Hospital of Harbin Medical University, China

There is increasing evidence indicating that inflammation represents a key pathological component of Alzheimer’s disease (AD). A possible factor that may contribute to this process is netrin-1, a neuronal guidance molecule. This molecule has been shown to exert an unexpected immunomodulatory function. However, the potential changes and correlations of netrin-1 with T helper 17/regulatory T cells (Th17/Tregs) as related to inflammation in AD has yet to be examined. In this study, netrin-1 and Th17/Tregs balance were investigated, and the relationship among netrin-1, Th17/Tregs and cognitive function were analyzed in a rat model of AD. In this model, a bilateral intracerebroventricular administration of Amyloid β1-42 (Aβ1-42) was used to produce spatial learning and memory deficits, as well as increased neuronal apoptosis, which were detected 7 days after injection for AD7d group and 14 days for AD14d group. Netrin-1 concentrations were significantly down regulated in both serum and cerebrospinal fluid (CSF) of these AD rats, effects which were strongly correlated with cognitive deficits. Increased levels of interleukin (IL)-17 and deceased IL-10 were observed in both the circulation and CSF and were also correlated with the percent of time spent in the target quadrant of AD in these rats. These changes resulted in netrin-1 concentrations being negatively correlated with IL-17 but positively correlated with IL-10 concentrations in the serum and CSF. We also found that the Th17/Tregs balance was disrupted in these AD rats. Collectively, these findings reveal that the reduction in netrin-1 and correlated disruption of Th17/Tregs balance in AD rats, may diminish the immunosuppressive effect of netrin-1 on Th17/Tregs in AD pathogenesis.

Keywords: Alzheimer’s disease, Inflammation, Netrin-1, Th17, Tregs

Received: 15 Jan 2019; Accepted: 10 May 2019.

Edited by:

Laura Morelli, Leloir Institute Foundation (FIL), Argentina

Reviewed by:

PATRICIA LAGOS, Departamento de Fisiología, Facultad de Medicina, Universidad de la República, Uruguay
Sonia Do Carmo, McGill University, Canada  

Copyright: © 2019 Sun, Ju, Wang, Zhang, Ding, Zhang, An, Xun, Li, Lu, Zhang and Chi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Lijun Chi, Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang Province, China,