Microglial Activation Is Modulated by Captopril: in Vitro and in Vivo Studies
Autor: | Sigal Fleisher-Berkovich, Nofar Torika, Keren Asraf, Ron N. Apte |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Inflammation Pharmacology angiotensin II Neuroprotection Nitric oxide lcsh:RC321-571 glial inflammation 03 medical and health sciences chemistry.chemical_compound Cellular and Molecular Neuroscience 0302 clinical medicine angiotensin-converting enzyme medicine Cognitive decline lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Original Research biology Angiotensin-converting enzyme Captopril Angiotensin II captopril 030104 developmental biology chemistry biology.protein Tumor necrosis factor alpha medicine.symptom Alzheimer’s disease 030217 neurology & neurosurgery Neuroscience medicine.drug |
Zdroj: | Frontiers in Cellular Neuroscience, Vol 12 (2018) Frontiers in Cellular Neuroscience |
ISSN: | 1662-5102 |
DOI: | 10.3389/fncel.2018.00116 |
Popis: | 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. |
Databáze: | OpenAIRE |
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