Modified Levels of Renin Angiotensin Related Components in the Frontal Cortex and Hippocampus were Associated with Neuroinflammation and Lower Neuroprotective Effects of NGF During Acute Hepatic Encephalopathy in Mice

Title:Modified Levels of Renin Angiotensin Related Components in the Frontal Cortex and Hippocampus were Associated with Neuroinflammation and Lower Neuroprotective Effects of NGF During Acute Hepatic Encephalopathy in Mice

Volume: 29 Issue: 12

Author(s): Natália Katley Oliveira, Eliana Cristina de Brito Toscano, Bruna da Silva Oliveira, Luiza Cioglia Dias Lima, Ana Cristina Simões e Silva, Aline Silva de Miranda*, Antônio Lúcio Teixeira and Milene Alvarenga Rachid*

Affiliation:

• Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, MG, Brazil

• Departamento de Patologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, MG, Brazil

Keywords: Angiotensin-renin system, cytokines, hepatic encephalopathy, mice, thioacetamide, neurotrophic factors.

Abstract:

Background: Hepatic encephalopathy (HE) is a neuropsychiatric syndrome that involves cognitive and motor dysfunctions due to hepatic failure. The clinical and experimental studies suggest that the angiotensin (Ang) converting enzyme (ACE), Ang II, and angiotensin type 1 receptor (AT1R), which compose the classical pathway of the renin–angiotensin system (RAS), exacerbate neuroinflammation in different neurologic diseases. Conversely, Ang-(1-7), ACE2, and Mas receptor, which integrate the alternative RAS axis, have been shown as promising therapeutic targets in neuropsychiatric disorders, leading to neuroprotection.

Objective: This study aimed to investigate the potential participation of the RAS components in thioacetamide (TAA)-induced HE in mice.

Methods: We also evaluated the levels of neurotrophic factors, pro-inflammatory cytokines, and chemokine in the central nervous system of TAA-induced HE in mice. Mice were submitted to acute liver failure induced by TAA administration by intraperitoneal route. Measurements of RAS components (ACE, Ang II, ACE2 and Ang1-7) and neurotrophic factors (BDNF, GDNF and NGF) were obtained by ELISA assay. Pro-inflammatory cytokines (TNF, IFN-γ, IL-6, IL-12p70) and the chemokine (CCL2) were quantified by cytometric bead array. The student’s t-test was applied for statistical analysis.

Results: Mice presented increased cortical levels of ACE, while Ang-(1-7) levels were decreased in cortical and hippocampal samples compared to controls. Moreover, HE mice had an increase in the Ang II/Ang-(1-7) ratio along with reduced levels of neural growth factor (NGF) in the prefrontal cortex. They also showed elevated levels of IFN-γ and CCL2 in the prefrontal cortex and of TNF, IL-6, IL-12, and CCL2 in the hippocampus compared with controls.

Conclusion: This study suggested that the reduction of components of the alternative RAS axis was associated with the deleterious effects of neuroinflammation and lower neuroprotective effects of NGF during TAA-induced HE.

Cite this article as:

Oliveira Katley Natália, de Brito Toscano Eliana Cristina, Silva Oliveira Bruna da, Dias Lima Luiza Cioglia, Simões e Silva Ana Cristina, de Miranda Aline Silva*, Teixeira Lúcio Antônio and Rachid Alvarenga Milene*, Modified Levels of Renin Angiotensin Related Components in the Frontal Cortex and Hippocampus were Associated with Neuroinflammation and Lower Neuroprotective Effects of NGF During Acute Hepatic Encephalopathy in Mice, Protein & Peptide Letters 2022; 29 (12) . https://dx.doi.org/10.2174/0929866529666220825150025