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.