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. 2019 Mar-Apr;10(2):119-135.
doi: 10.32598/bcn.9.10.170. Epub 2019 Mar 1.

Interactive Effects of Exercise, Sex Hormones, and Transient Congenital Hypothyroidism on Long-Term Potentiation in Hippocampal Slices of Rat Offspring

Leila Derafshpour  1   2 , Ehsan Saboory  2 , Abbas Ali Vafaei  1 , Ali Rashidy-Pour  1 , Shiva Roshan-Milani  2 , Yousef Rasmi  3 , Yousef Panahi  4 , Hamidreza Sameni  5
Affiliations

Interactive Effects of Exercise, Sex Hormones, and Transient Congenital Hypothyroidism on Long-Term Potentiation in Hippocampal Slices of Rat Offspring

Leila Derafshpour et al. Basic Clin Neurosci. 2019 Mar-Apr.

Abstract

Introduction: The long-term adverse effects of transient thyroid function abnormalities at birth on intellectual development are proven. The effect of exercise increases in the presence of sex hormones. The current study aimed at investigating the possibility that a combination of sex hormones and exercise has synergistic effects on neural plasticity in Transient Congenital Hypothyroidism (TCH) rats.

Methods: To induce hypothyroidism in the mothers, Propylthiouracil (PTU) was added to drinking water (100 mg/L) on the 6th day of gestation and continued until the 21st Postnatal Day. From Postnatal Day (PND) 28 to 47, the female and male pups received 17β-estradiol and testosterone, respectively. The mild treadmill exercise began 30 minutes after the sex hormones or vehicle administration. On PND 48, electrophysiological experiments were performed on brain slices.

Results: Increase of Long-Term Potentiation (LTP) was observed in sedentary-non-hormone female rats of TCH group, compared with that of the control. The exercise enhanced LTP in control rats, but the hormones showed no significant effect. The effect of exercise and sex hormone was not significant in the TCH group. The combination of exercise and testosterone enhanced LTP in TCH male rats, while the combination of exercise and estradiol or each of them individually did not produce such an effect on LTP in TCH female rats.

Conclusion: The study findings showed an increase in excitatory transmission despite the returning of thyroid hormone levels to normal range in TCH female rats. Also a combination treatment including exercise and testosterone enhanced LTP in male rats of TCH group, which was a gender-specific event.

Keywords: Exercise; Hypothyroid; Long-Term Potentiation; Sex hormones.

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Conflict of interest statement

Conflict of interest The authors declared no conflict of interest.

Figures

Figure 1.
Figure 1.
PS amplitude in CA1 of hippocampus in hypothyroid rats in 60 minutes after LTP induction A: Effects of treadmill exercise; B: Effects of hormone; C: Effects of hypothyroid; D: Effects of gender; The repeated measures ANOVA (4-way) revealed significant exect of exercise (P= 0.004); * indicates the significant effects of exercise compared with those of non-exersice.
Figure 2.
Figure 2.
Effects of treadmill exercise and sex hormones on mean of PS amplitude (% baseline) in male (A) and female (B) rats of the control and TCH group during 60 minutes after HFs Panel A: mean of PS amplitude was significantly higher in TE/HYP/H subgroup compared to TE/CON/H, SED/HYP/NH, SED/HYP/H, and TE/HYP/NH subgroups. & indicates P=0.014, @ indicates P=0.015, ^ indicates P=0.014, and ! indicates P=0.036 compared with the TE/CON/H, SED/HYP/NH, SED/HYP/H and TE/HYP/NH subgroups, respectively; Panel B: mean of PS amplitude was significantly higher in TE/CON/H subgroup compared with SED/CON/NH subgroup. The results are expressed as Mean±SEM (4-way ANOVA); * P=0.047
Figure 3.
Figure 3.
Effects of treadmill exercise and sex hormones on ampli 60 of PS (% baseline) in male (A) and female (B) rats of the control and TCH group at time point 60 minutes after HFs Panel A: Mean of ampli 60 of PS (% baseline) was significantly higher in TE/HYP/H subgroup compared to SED/HYP/H, SED/HYP/NH, TE/HYP/NH, and TE/CON/H subgroups. ^^ indicates P=0.006, @@ indicates P=0.002, !! indicates P=0.008, and && idicates P=0.003 compared to the SED/HYP/H, SED/HYP/NH, TE/HYP/NH and TE/CON/H subgroups, respectively; Panel B: Mean of ampli 60 of PS (% baseline) were significantly higher in TE/CON/H and TE/CON/NH subgroups compared with SED/CON/NH subgroup. The data are expressed as Mean±SEM (4-way ANOVA); * P=0.018; ** P=0.008
Figure 4.
Figure 4.
Effects of treadmill exercise and sex hormones on mean of PS amplidiff60 (PS amplitude difference of two time points of 5 and 60 minutes after HFs) (% baseline) in male (A) and female (B) rats of the control and TCH groups Panel A: mean of PS amplidiff60 (% baseline) was significantly higher in TE/HYP/H subgroup compared with SED/HYP/H, SED/HYP/NH, TE/HYP/NH, and TE/CON/H subgroups. ^^ indicates P=0.003, @@@ indicates P=0.001, !! indicates P=0.002, and &&& indicates P=0.001 compared with the SED/HYP/H, SED/HYP/NH, TE/HYP/NH, and TE/CON/H subgroups, respectively; Panel B: mean of PS amplidiff60 (% baseline) was significantly higher in TE/CON/NH and TE/CON/H subgroups compared to SED/CON/NH andSED/CON/H subgroups. *** indicates P=0.001 and compared with the SED/CON/NH, ## indicates P=0.003 and P=0.002 compared with the SED/CON/H.As well, mean of PS of amplidiff60 (% baseline) was significantly higher in TE/CON/NH H subgroup compared with TE/HYP/NH; !! indicates P=0.010 compared with the TE/HYP/NH. The data are expressed as Mean±SEM (4-way ANOVA).
Figure 5.
Figure 5.
The fEPSP slope in CA1 of the hippocampus in hypothyroid rats in 60 minutes after LTP induction A) Effects of treadmill exercise; B) Effects of hormone; C) Effects of hypothyroid; D) Effects of gender; The repeated measurements ANOVA (4-way) revealed significant exect of hypothyroid (P= 0.039).
Figure 6.
Figure 6.
Effects of treadmill exercise and sex hormones on fEPSP slope (% baseline) in male (A) and female (B) rats of the control and TCH groups 60 minutes after HFs Panel A: Effects of treadmill exercise and sex hormones on mean of fEPSP slope in male rats were not significant; Panel B: mean of fEPSP slope was significantly higher in SED/HYP/NH subgroup compared with SED/CON/NH subgroup. The data are expressed as Mean±SEM (4-way ANOVA); * P=0.041
Figure 7.
Figure 7.
Effects of treadmill exercise and sex hormones on slop60 of fEPSP (% baseline) in male (A) and female (B) rats of control and TCH groups at 60 minutes after HFs Panel A: Mean of slop60 (% baseline) was significantly higher in TE/HYP/H subgroup compared to SED/HYP/NH and TE/CON/H sub-groups. @ indicates P=0.041 and & indicates P=0.046 compared with the SED/HYP/NH and TE/CON/H subgroups, respectively; Panel B: Mean of slop60 (% baseline) was significantly higher in SED/HYP/NH subgroup compared with SED/CON/NH subgroup. The data are expressed as Mean±SEM (4-way ANOVA); * P=0.027
Figure 8.
Figure 8.
Effects of treadmill exercise and sex hormones on mean of slopdiff60 (sloe of fEPSP difference 5 and 60 minutes after HFs) (% baseline) in male (A) and female (B) rats of the control and TCH groups Panel A: Mean of slopdiff60 (% baseline) was significantly higher in TE/CON/NH subgroup compared with SED/CON/NH and SED/CON/H subgroups. * indicates P=0.038 and # indicates P=0.015, compared with the SED/CON/NH and SED/CON/H sub-groups, respectively; as well, the mean of slopdiff60 (% baseline) was significantly higher in TE/HYP/H subgroup compared to SED/HYP/NH and TE/CON/H sub-groups. @ indicates P=0.046 and & indicates P=0.018 compared with the SED/HYP/NH and TE/CON/H subgroups, respectively; Panel B: mean of slopdiff60 (% baseline) was significantly higher in TE/CON/H subgroup compared to SED/CON/NH and SED/CON/H subgroups. * indicates P=0.027 and # indicates P=0.026 compared to the SED/CON/NH and SED/CON/H subgroups respectively, as well, the mean of slopdiff60 (% baseline) was significantly higher in TE/CON/NH subgroup compared to SED/CON/NH, SED/CON/H and TE/HYP/NH sub-groups. * indicates P=0.012, # indicates P=0.012, and ! indicates P=0.018 compared to the SED/CON/NH, SED/CON/H, and TE/HYP/NH subgroups, respectively. The data are expressed as Mean±SEM (4-way ANOVA).
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