Effects Of Age And Sex On Levels Of Munc18-1 In Brain And TH In Serum Of Outbred Stocks Mice

Background The gradual decline of learning and memory with age is a common phenomenon in humans and rodents. However, the underlying neuromechanism of the age-related impairment of learning and memory is not yet clear. The current view is that changes in levels of synaptic protein in the hippocampus and neocortex may be one of the reasons causing learning and memory decline. Munc18-1 is a critical protein involved in regulation of SNARE complex formation and it is essential for vesicle exocytosis. But the change of the Munc18-1 during normal aging is not clear. The relationship between serum thyroid hormone (TH) and cognition has been confirmed. However, the dependablity between changes of synaptic proteins and the TH levels have not been researched. Due to the limitations of direct study of neuromechanism of brain aging in human, we turn to outbred stocks mice (Kunming mice and ICR mice) to simulate human aging.Objective①To explore the effects of age and sex on the levels of Munc18-1 in different brain regions and on the TH level in serum.②To explore the correlation between the TH level and Munc18-1.Methods Three age groups in the Kunming mice (old group aged 22 months, middle-aged group at age of 11 months and young group aged 6 months) and two age groups in the ICR mice (middle-aged group at 12 months and young group at 7 months) were used. The Munc18-1 andβ-actin (reference protein) in dorsal hippocampus, ventral hippocampus, frontal lobe, parietal lobe and olfactory bulb were detected respectively by Western blot, and the ratio of the Munc18-1 to theβ-actin gray-scale value was viewed as the relative content of the Munc18-1. The serum TH level was detected by radioimmunoassay. The statistical analyses were completed using analysis of variance and Spearman's rank correlation.Results①For the Kunming mice, the Munc18-1 relative amount in the dorsal hippocampus in the 22-month-old group was higher than that in the middle-aged and young group (Ps < 0.05), with more significantly in the elderly females (Ps < 0.05), and there was no difference between the middle-aged and young groups (P > 0.05). For the ICR mice, the Munc18-1 relative amount in the dorsal hippocampus in the 12-month-old group was higher than that in the young group (Ps < 0.05), with more significantly in the middle-aged females (Ps < 0.05).②For the Kunming mice, the levels of both serum free triiodothyronine (FT3) and free thyroxine (FT4) in the 22-month-old group were lower than those in the young group (Ps < 0.05), and FT3 level was lower compared to the middle-aged group (P < 0.05), with more significantly in the elderly females (Ps < 0.05), and there were no differences between the middle-aged and young groups (P > 0.05). For the ICR mice, the level of serum FT3 in the middle-aged group was lower relative to the young group (P < 0.05), with more significantly in the middle-aged females (P < 0.05).③There was a negative correlation between the Munc18-1 relative amount in the dorsal hippocampus and the level of serum FT3 in the both Kunming and ICR mice (Ps < 0.05).Conclusion In outbred stocks mice:①the Munc18-1 relative amount in dorsal hippocampus significantly increased with aging, with more significantly in females;②the serum TH level significantly decreased with aging, with more singnificantly in females;③The serum TH decrement may be involved in the Munc18-1increment in dorsal hippocampus.