Microglial Activation Is Modulated by Captopril: in Vitro and in Vivo Studies
The renin-angiotensin system (RAS) is an important peripheral system involved in homeostasis modulation, with angiotensin II (Ang II) serving as the main effector hormone. The main enzyme involved in Ang II formation is angiotensin-converting enzyme (ACE). ACE inhibitors (ACEIs) such as captopril (C...
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Frontiers Media S.A.
2018-05-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fncel.2018.00116/full |
| _version_ | 1818528372728266752 |
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| author | Keren Asraf Nofar Torika Ron N. Apte Sigal Fleisher-Berkovich |
| author_facet | Keren Asraf Nofar Torika Ron N. Apte Sigal Fleisher-Berkovich |
| author_sort | Keren Asraf |
| collection | DOAJ |
| description | The renin-angiotensin system (RAS) is an important peripheral system involved in homeostasis modulation, with angiotensin II (Ang II) serving as the main effector hormone. The main enzyme involved in Ang II formation is angiotensin-converting enzyme (ACE). ACE inhibitors (ACEIs) such as captopril (Cap) are predominantly used for the management of hypertension. All of the components of the RAS have also been identified in brain. Centrally located hormones such as Ang II can induce glial inflammation. Moreover, in Alzheimer’s disease (AD) models, where glial inflammation occurs and is thought to contribute to the propagation of the disease, increased levels of Ang II and ACE have been detected. Interestingly, ACE overexpression in monocytes, migrating to the brain was shown to prevent AD cognitive decline. However, the specific effects of captopril on glial inflammation and AD remain obscure. In the present study, we investigated the effect of captopril, given at a wide concentration range, on inflammatory mediators released by lipopolysaccharide (LPS)-treated glia. In the current study, both primary glial cells and the BV2 microglial cell line were used. Captopril decreased LPS-induced nitric oxide (NO) release from primary mixed glial cells as well as regulating inducible NO synthase (iNOS) expression, NO, tumor necrosis factor-α (TNF-α) and induced interleukin-10 (IL-10) production by BV2 microglia. We further obtained data regarding intranasal effects of captopril on cortical amyloid β (Aβ) and CD11b expression in 5XFAD cortex over three different time periods. Interestingly, we noted decreases in Aβ burden in captopril-treated mice over time which was paralleled by increased microglial activation. These results thus shed light on the neuroprotective role of captopril in AD which might be related to modulation of microglial activation. |
| first_indexed | 2024-12-11T06:48:56Z |
| format | Article |
| id | doaj.art-90e2736161fb4d8e8c701493860cc271 |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-11T06:48:56Z |
| publishDate | 2018-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-90e2736161fb4d8e8c701493860cc2712022-12-22T01:16:58ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022018-05-011210.3389/fncel.2018.00116344214Microglial Activation Is Modulated by Captopril: in Vitro and in Vivo StudiesKeren Asraf0Nofar Torika1Ron N. Apte2Sigal Fleisher-Berkovich3Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev, Beersheba, IsraelDepartment of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev, Beersheba, IsraelThe Shraga Segal Department of Microbiology, Immunology and Genetics, Ben Gurion University of the Negev, Beersheba, IsraelDepartment of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev, Beersheba, IsraelThe renin-angiotensin system (RAS) is an important peripheral system involved in homeostasis modulation, with angiotensin II (Ang II) serving as the main effector hormone. The main enzyme involved in Ang II formation is angiotensin-converting enzyme (ACE). ACE inhibitors (ACEIs) such as captopril (Cap) are predominantly used for the management of hypertension. All of the components of the RAS have also been identified in brain. Centrally located hormones such as Ang II can induce glial inflammation. Moreover, in Alzheimer’s disease (AD) models, where glial inflammation occurs and is thought to contribute to the propagation of the disease, increased levels of Ang II and ACE have been detected. Interestingly, ACE overexpression in monocytes, migrating to the brain was shown to prevent AD cognitive decline. However, the specific effects of captopril on glial inflammation and AD remain obscure. In the present study, we investigated the effect of captopril, given at a wide concentration range, on inflammatory mediators released by lipopolysaccharide (LPS)-treated glia. In the current study, both primary glial cells and the BV2 microglial cell line were used. Captopril decreased LPS-induced nitric oxide (NO) release from primary mixed glial cells as well as regulating inducible NO synthase (iNOS) expression, NO, tumor necrosis factor-α (TNF-α) and induced interleukin-10 (IL-10) production by BV2 microglia. We further obtained data regarding intranasal effects of captopril on cortical amyloid β (Aβ) and CD11b expression in 5XFAD cortex over three different time periods. Interestingly, we noted decreases in Aβ burden in captopril-treated mice over time which was paralleled by increased microglial activation. These results thus shed light on the neuroprotective role of captopril in AD which might be related to modulation of microglial activation.http://journal.frontiersin.org/article/10.3389/fncel.2018.00116/fullAlzheimer’s diseaseangiotensin IIangiotensin-converting enzymecaptoprilglial inflammation |
| spellingShingle | Keren Asraf Nofar Torika Ron N. Apte Sigal Fleisher-Berkovich Microglial Activation Is Modulated by Captopril: in Vitro and in Vivo Studies Frontiers in Cellular Neuroscience Alzheimer’s disease angiotensin II angiotensin-converting enzyme captopril glial inflammation |
| title | Microglial Activation Is Modulated by Captopril: in Vitro and in Vivo Studies |
| title_full | Microglial Activation Is Modulated by Captopril: in Vitro and in Vivo Studies |
| title_fullStr | Microglial Activation Is Modulated by Captopril: in Vitro and in Vivo Studies |
| title_full_unstemmed | Microglial Activation Is Modulated by Captopril: in Vitro and in Vivo Studies |
| title_short | Microglial Activation Is Modulated by Captopril: in Vitro and in Vivo Studies |
| title_sort | microglial activation is modulated by captopril in vitro and in vivo studies |
| topic | Alzheimer’s disease angiotensin II angiotensin-converting enzyme captopril glial inflammation |
| url | http://journal.frontiersin.org/article/10.3389/fncel.2018.00116/full |
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