Thiamine is a vitamin belonging to the B-complex, also known as vitamin B1 (T+). Its deficiency in the body can result in disorders related to heart failure and neurological diseases. Little is known about the mechanisms related to thiamine deficiency (TD) induced neurodegeneration, and the differences in responses to TD between male and female individuals. Using a model of nutritional deficiency of thiamine in association with amprolium, using intraperitoneal injections at different doses (20, 40, 60 and 80 mg/kg) and different times (05, 10, 15 and 20 days), we investigated the modulation of intracellular signaling pathways in the nervous system of male and female Swiss mice, and also the involvement of oxidative stress and inflammation in the modulation of cell signaling and behavior in female mice. In male mice, we observed progressive increase in phosphorylation of ERK1/2 in both cerebral cortex and thalamus in response to amprolium dose. In females, we did not observe a progressive response in ERK1/2 modulation in relation to the increase in amprolium dose, evidencing an abrupt increase in phosphorylation at the highest doses used, 60 and 80 mg/kg. In male mice, we also observed increased phosphorylation of ERK1/2 in the cerebral cortex at all times of thiamine deficiency treatment with amprolium. In females, the profile of ERK1/2 modulation upon deficiency with amprolium was similar in both structures at the different treatment times. Furthermore, we observed significant involvement of oxidative stress and inflammation in TD in females, with negative impacts on body weight gain, motor behavior, and their involvement in modulation of the ERK1/2 pathway, demonstrated through attenuation of effects with the use of the antioxidant Trolox and the anti-inflammatory dimethyl sulfoxide. The results obtained show some differences between male and female mice regarding the modulation of ERK1/2 in the central nervous system and in behavioral aspects, but highlight the feasibility of using females in experimental models to study neurodegenerative effects associated with TD. Furthermore, the study proves the efficiency of the nutritional thiamine deficiency model associated with amprolium.
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