Decreased Netrin-1 and Correlated Th17/Tregs Balance Disorder in Aβ1–42 Induced Alzheimer’s Disease Model Rats
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 functio...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2019-05-01
|
| Series: | Frontiers in Aging Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fnagi.2019.00124/full |
| _version_ | 1828862981188878336 |
|---|---|
| author | Lina Sun Ting Ju Tianhang Wang Liang Zhang Feifan Ding Yan Zhang Ran An Yilei Sun You Li Yidan Lu Xin Zhang Lijun Chi |
| author_facet | Lina Sun Ting Ju Tianhang Wang Liang Zhang Feifan Ding Yan Zhang Ran An Yilei Sun You Li Yidan Lu Xin Zhang Lijun Chi |
| author_sort | Lina Sun |
| collection | DOAJ |
| description | 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 the correlated disruption of Th17/Tregs balance in AD rats may diminish the immunosuppressive effect of netrin-1 on Th17/Tregs in AD pathogenesis. |
| first_indexed | 2024-12-13T03:34:48Z |
| format | Article |
| id | doaj.art-c1e08062eeeb4f928931c8a5605247d8 |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-12-13T03:34:48Z |
| publishDate | 2019-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-c1e08062eeeb4f928931c8a5605247d82022-12-22T00:01:04ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652019-05-011110.3389/fnagi.2019.00124448464Decreased Netrin-1 and Correlated Th17/Tregs Balance Disorder in Aβ1–42 Induced Alzheimer’s Disease Model RatsLina SunTing JuTianhang WangLiang ZhangFeifan DingYan ZhangRan AnYilei SunYou LiYidan LuXin ZhangLijun ChiThere 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 the correlated disruption of Th17/Tregs balance in AD rats may diminish the immunosuppressive effect of netrin-1 on Th17/Tregs in AD pathogenesis.https://www.frontiersin.org/article/10.3389/fnagi.2019.00124/fullAlzheimer’s diseaseinflammationnetrin-1Th17Tregs |
| spellingShingle | Lina Sun Ting Ju Tianhang Wang Liang Zhang Feifan Ding Yan Zhang Ran An Yilei Sun You Li Yidan Lu Xin Zhang Lijun Chi Decreased Netrin-1 and Correlated Th17/Tregs Balance Disorder in Aβ1–42 Induced Alzheimer’s Disease Model Rats Frontiers in Aging Neuroscience Alzheimer’s disease inflammation netrin-1 Th17 Tregs |
| title | Decreased Netrin-1 and Correlated Th17/Tregs Balance Disorder in Aβ1–42 Induced Alzheimer’s Disease Model Rats |
| title_full | Decreased Netrin-1 and Correlated Th17/Tregs Balance Disorder in Aβ1–42 Induced Alzheimer’s Disease Model Rats |
| title_fullStr | Decreased Netrin-1 and Correlated Th17/Tregs Balance Disorder in Aβ1–42 Induced Alzheimer’s Disease Model Rats |
| title_full_unstemmed | Decreased Netrin-1 and Correlated Th17/Tregs Balance Disorder in Aβ1–42 Induced Alzheimer’s Disease Model Rats |
| title_short | Decreased Netrin-1 and Correlated Th17/Tregs Balance Disorder in Aβ1–42 Induced Alzheimer’s Disease Model Rats |
| title_sort | decreased netrin 1 and correlated th17 tregs balance disorder in aβ1 42 induced alzheimer s disease model rats |
| topic | Alzheimer’s disease inflammation netrin-1 Th17 Tregs |
| url | https://www.frontiersin.org/article/10.3389/fnagi.2019.00124/full |
| work_keys_str_mv | AT linasun decreasednetrin1andcorrelatedth17tregsbalancedisorderinab142inducedalzheimersdiseasemodelrats AT tingju decreasednetrin1andcorrelatedth17tregsbalancedisorderinab142inducedalzheimersdiseasemodelrats AT tianhangwang decreasednetrin1andcorrelatedth17tregsbalancedisorderinab142inducedalzheimersdiseasemodelrats AT liangzhang decreasednetrin1andcorrelatedth17tregsbalancedisorderinab142inducedalzheimersdiseasemodelrats AT feifanding decreasednetrin1andcorrelatedth17tregsbalancedisorderinab142inducedalzheimersdiseasemodelrats AT yanzhang decreasednetrin1andcorrelatedth17tregsbalancedisorderinab142inducedalzheimersdiseasemodelrats AT ranan decreasednetrin1andcorrelatedth17tregsbalancedisorderinab142inducedalzheimersdiseasemodelrats AT yileisun decreasednetrin1andcorrelatedth17tregsbalancedisorderinab142inducedalzheimersdiseasemodelrats AT youli decreasednetrin1andcorrelatedth17tregsbalancedisorderinab142inducedalzheimersdiseasemodelrats AT yidanlu decreasednetrin1andcorrelatedth17tregsbalancedisorderinab142inducedalzheimersdiseasemodelrats AT xinzhang decreasednetrin1andcorrelatedth17tregsbalancedisorderinab142inducedalzheimersdiseasemodelrats AT lijunchi decreasednetrin1andcorrelatedth17tregsbalancedisorderinab142inducedalzheimersdiseasemodelrats |