L-Metiyoninin Neden Olduğu Nörokognitif Yıkılma: Bir Nörodejenerasyon Fare Modeli

Abstract

Objective: Neurodegenerative diseases are defined by irreversible neuronal and glial loss in the central nervous system. Despite sharing neural cell loss as a common denominator, they differ in their clinical manifestations in many aspects. We aimed to analyze the behavioral changes and underlying immunohistochemical changes in mice caused by an environmental stressor, l-methionine, to assess the spectrum of clinical findings observed in these diseases. Material and Method: In this study, the mice are divided into 4 groups: female-control (n=13), female-methionine (n=12), male-control (n=12), male-methionine (n=13) to perform immunohistochemical and behavioral tests. Starting from post-natal week 6, the mice were either administered water or 8.2g/kg l-methionine for 12 weeks. Consequently, they underwent a series of behavioral tests to assess anxiety, depression, memory/learning, and motor functions. We performed immunohistochemical analysis on mice (3 randomly chosen mice from each group prior to behavior tests) which did not undergo behavioral tests. Results: Compared to the control group, mice who received l-methionine were found to have significant hippocampus dependent spatial memory deficits. No significant differences were found in regards to anxiety and depression. Our immunohistochemical analysis showed a significantly increased senescent astrocyte to all astrocyte ratio in dentate gyrus of hippocampal formation. Conclusion: Chronic administration of an oral high dose of l-methionine results in hippocampus dependent memory decline in mice. Parallel to this finding, the ratio of senescent astrocytes to all astrocytes increased in dentate gyrus.