| Popis: |
Memory impairment is a feature of several diseases and detrimental as aging population have increased worldwide. Sustained advanced glycation end products (AGEs) receptor (RAGE) activation triggers the production of reactive oxygen species and inflammatory response, leading to neuronal dysfunction and neurodegenerative disorders. Methylglyoxal (MGO) is the most relevant and reactive glycating agent in vivo, leading to the formation of AGEs. Here, we investigated the role of RAGE on the memory impairment induced by MGO. Swiss female mice were treated for 11 days with MGO, FPS‑ZM1 (a high‑affinity RAGE antagonist), or the combination of both. Locomotor activity was not impaired by the treatments, as evaluated by the open field and spontaneous alternation test. MGO treatment impaired short‑ and long‑term spatial memory in the object location task, caused deficits on the short‑term aversive memory in the step‑down inhibitory avoidance task, and decreased working memory performance as evaluated by the Y‑maze spontaneous alternation test. FPS‑ZM1 treatment abolished deficits on the short‑term aversive memory and working memory, but was unable to prevent the impairment in short‑term or long‑term spatial memory. Since the addition of RAGE antagonist in co‑treatment with MGO protected mice from the aversive and working memory deficits, AGEs generated by the MGO treatment would be involved in the memory impairment due to RAGE activation. Therefore, further studies are required to establish the involvement of RAGE in the MGO‑induced memory impairment. Nevertheless, our results suggested FPS‑ZM1 treatment as a promising new therapeutic strategy to prevent cognitive dysfunction caused by dicarbonyl stress, further investigation is required to confirm our findings. |
