Aluminum chloride impairs learning and memory by P2X7 and A2A-receptor stimulations in hippocampus of mice
Autor: | Heidrich G, Assmann Ce, Reichert Kp, Costa Pd, Silva ADd, Bottari Nb, Dressler, Lopes Tf, Schetinger Mrc, Morsch Vmm |
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Rok vydání: | 2021 |
Předmět: | |
DOI: | 10.21203/rs.3.rs-329182/v1 |
Popis: | Aluminum (Al) is considered a neurotoxic agent for biological systems and is recognized as a risk factor for neurodegenerative diseases. Al exposure occurs through the environment, water and human diet. The Al cationic form (Al3+) has been associated with major deleterious effects on the central nervous system. The aim of this study was to investigate a possible mechanism that links Al and neurodegeneration in vivo. Here, we evaluated memory tests, purinergic signaling and inflammatory markers during long-term oral exposure to Al of mice in the total hippocampus. For this study, Swiss mice were divided into three groups: control (CT) group, AlCl3 50 mg/kg group and AlCl3 100 mg/kg group. The animals were orally treated with saline or Al3+ at AlCl3 form for 30 days. The memory parameters, body and brain weight, Al3+ levels, DNA damage, enzyme activities, purinergic receptors and cytokine densities were assessed on the hippocampus of mice intoxicated with Al3+. Our results reveal that Al3+ was able to reduce brain weight and accumulate in the hippocampus of animals treated with 100 mg/kg of salt. In addition, Al3+ causes memory deficits and DNA damage. The adenosine triphosphate (ATP) hydrolysis was also affected by Al3+. Our results point to an increase in nucleoside triphosphate diphosphohydrolase (NTPDase), 5´-nucleotidase (5’-NT) and adenosine deaminase (ADA) activities. In addition, Al3+ increases P2X7 and A2A receptor density, as IL-1β proinflammatory cytokine. Taken together, we suggest that Al3+ can cause memory loss through DNA damage and alterations to the purinergic system through the proinflammatory process. |
Databáze: | OpenAIRE |
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