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The Posterodorsal Medial Amygdala Regulates the Timing of Puberty Onset in Female Rats.

Li XF, Hu MH, Hanley BP, Lin YS, Poston L, Lightman SL, O'Byrne KT - Endocrinology (2015)

Bottom Line: In both dietary groups, MePD lesions resulted in an increase in socialization and a decrease in play fighting behavior.In conclusion, our results suggest the MePD regulates the timing of puberty via a novel mechanism independent of change in body weight and caloric intake.MePD glutamatergic systems advance the timing of puberty whereas local GABAergic activation results in a delay.

View Article: PubMed Central - PubMed

Affiliation: Division of Women's Health (X.F.L., M.H.L., B.P.H., Y.S.L., L.P., K.T.O.), Faculty of Life Sciences and Medicine, King's College London, Guy's Campus, London SE1 1UL, United Kingdom; and Henry Wellcome Laboratory for Integrative Neuroscience and Endocrinology (S.L.L.), University of Bristol, Bristol BS1 3NY, United Kingdom.

ABSTRACT
Obesity is the major risk factor for early puberty, but emerging evidence indicates other factors including psychosocial stress. One key brain region notable for its role in controlling calorie intake, stress, and behavior is the amygdala. Early studies involving amygdala lesions that included the medial nucleus advanced puberty in rats. More recently it was shown that a critical site for lesion-induced hyperphagia and obesity is the posterodorsal subnucleus of the medial amygdala (MePD), which may explain the advancement of puberty. Glutamatergic activity also increases in the MePD during puberty without a corresponding γ-aminobutyric acid (GABA)ergic change, suggesting an overall activation of this brain region. In the present study, we report that neurotoxic lesioning of the MePD advances puberty and increases weight gain in female rats fed a normal diet. However, MePD lesioned rats fed a 25% nonnutritive bulk diet also showed the dramatic advancement of puberty but without the increase in body weight. In both dietary groups, MePD lesions resulted in an increase in socialization and a decrease in play fighting behavior. Chronic GABAA receptor antagonism in the MePD from postnatal day 21 for 14 days also advanced puberty, increased socialization, and decreased play fighting without altering body weight, whereas glutamate receptor antagonism delayed puberty and decreased socialization without affecting play fighting. In conclusion, our results suggest the MePD regulates the timing of puberty via a novel mechanism independent of change in body weight and caloric intake. MePD glutamatergic systems advance the timing of puberty whereas local GABAergic activation results in a delay.

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The effect of MePD lesions on estrous cyclicity in female rats fed with a normal chow diet (ND) or a 25% nonnutritive bulk diet (NND). Cyclicity was determined by analyzing the daily vaginal cytology for 12 consecutive days from the day of vaginal opening. A, In ND-fed rats, an MePD lesion resulted in a significant decrease in the percentage of normal estrous cycle vs sham-lesioned controls. Representative examples of estrous cycle are presented for sham-lesioned (B) and lesioned (C) rats. D, Cycle length was significantly extended after MePD lesion vs controls. E, Time spent in the metestrous stage was extended, whereas time spent in diestrus was decreased by MePD lesion compared with controls. F, Lesioning the MePD in NND fed rats also resulted in a significant decrease in the percentage of normal estrous cycle vs sham-lesion controls. Representative examples of the estrous cycle are presented for sham-lesioned (G) and lesioned (H) rats. I, MePD lesions also significantly extended cycle length compared with sham lesions in the NND fed rats. J, Time spent in the metestrous stage was extended, whereas time spent in diestrus was decreased by the MePD lesion compared with controls. Results are presented as means ± SEM. *, P < .05 vs controls (means ± SEM; n = 7–11 per group). D, diestrus; E, estrus; M, metestrus; P, proestrus.
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Figure 3: The effect of MePD lesions on estrous cyclicity in female rats fed with a normal chow diet (ND) or a 25% nonnutritive bulk diet (NND). Cyclicity was determined by analyzing the daily vaginal cytology for 12 consecutive days from the day of vaginal opening. A, In ND-fed rats, an MePD lesion resulted in a significant decrease in the percentage of normal estrous cycle vs sham-lesioned controls. Representative examples of estrous cycle are presented for sham-lesioned (B) and lesioned (C) rats. D, Cycle length was significantly extended after MePD lesion vs controls. E, Time spent in the metestrous stage was extended, whereas time spent in diestrus was decreased by MePD lesion compared with controls. F, Lesioning the MePD in NND fed rats also resulted in a significant decrease in the percentage of normal estrous cycle vs sham-lesion controls. Representative examples of the estrous cycle are presented for sham-lesioned (G) and lesioned (H) rats. I, MePD lesions also significantly extended cycle length compared with sham lesions in the NND fed rats. J, Time spent in the metestrous stage was extended, whereas time spent in diestrus was decreased by the MePD lesion compared with controls. Results are presented as means ± SEM. *, P < .05 vs controls (means ± SEM; n = 7–11 per group). D, diestrus; E, estrus; M, metestrus; P, proestrus.

Mentions: Estrous cyclicity was disrupted in the immediate postpubertal period of the MePD lesioned rats fed either normal diet or nonnutritive bulk diet (Figure 3; P < .05). Most the control rats showed normal 4- to 5-day estrous cycles (80% of the normal diet group, n = 10; 75% of the nonnutritive bulk diet group, n = 7), whereas only 38% for the normal diet group (n = 11) or 29% for the nonnutritive bulk diet group (n = 8) of the MePD-lesioned animals showed normal estrous cycles (Figure 3, A and F; P < .05). Representative examples of estrous cycles from each group are illustrated in Figure 3, B, C, G, and H. Cycle length was prolonged (Figure 3, D and I; P < .05) with an increase in metestrus and a decrease in diestrous phases evident in MePD-lesioned rats fed with normal diet or nonnutritive bulk diet (Figure 3, E and J; P < .05).


The Posterodorsal Medial Amygdala Regulates the Timing of Puberty Onset in Female Rats.

Li XF, Hu MH, Hanley BP, Lin YS, Poston L, Lightman SL, O'Byrne KT - Endocrinology (2015)

The effect of MePD lesions on estrous cyclicity in female rats fed with a normal chow diet (ND) or a 25% nonnutritive bulk diet (NND). Cyclicity was determined by analyzing the daily vaginal cytology for 12 consecutive days from the day of vaginal opening. A, In ND-fed rats, an MePD lesion resulted in a significant decrease in the percentage of normal estrous cycle vs sham-lesioned controls. Representative examples of estrous cycle are presented for sham-lesioned (B) and lesioned (C) rats. D, Cycle length was significantly extended after MePD lesion vs controls. E, Time spent in the metestrous stage was extended, whereas time spent in diestrus was decreased by MePD lesion compared with controls. F, Lesioning the MePD in NND fed rats also resulted in a significant decrease in the percentage of normal estrous cycle vs sham-lesion controls. Representative examples of the estrous cycle are presented for sham-lesioned (G) and lesioned (H) rats. I, MePD lesions also significantly extended cycle length compared with sham lesions in the NND fed rats. J, Time spent in the metestrous stage was extended, whereas time spent in diestrus was decreased by the MePD lesion compared with controls. Results are presented as means ± SEM. *, P < .05 vs controls (means ± SEM; n = 7–11 per group). D, diestrus; E, estrus; M, metestrus; P, proestrus.
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Related In: Results  -  Collection

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Figure 3: The effect of MePD lesions on estrous cyclicity in female rats fed with a normal chow diet (ND) or a 25% nonnutritive bulk diet (NND). Cyclicity was determined by analyzing the daily vaginal cytology for 12 consecutive days from the day of vaginal opening. A, In ND-fed rats, an MePD lesion resulted in a significant decrease in the percentage of normal estrous cycle vs sham-lesioned controls. Representative examples of estrous cycle are presented for sham-lesioned (B) and lesioned (C) rats. D, Cycle length was significantly extended after MePD lesion vs controls. E, Time spent in the metestrous stage was extended, whereas time spent in diestrus was decreased by MePD lesion compared with controls. F, Lesioning the MePD in NND fed rats also resulted in a significant decrease in the percentage of normal estrous cycle vs sham-lesion controls. Representative examples of the estrous cycle are presented for sham-lesioned (G) and lesioned (H) rats. I, MePD lesions also significantly extended cycle length compared with sham lesions in the NND fed rats. J, Time spent in the metestrous stage was extended, whereas time spent in diestrus was decreased by the MePD lesion compared with controls. Results are presented as means ± SEM. *, P < .05 vs controls (means ± SEM; n = 7–11 per group). D, diestrus; E, estrus; M, metestrus; P, proestrus.
Mentions: Estrous cyclicity was disrupted in the immediate postpubertal period of the MePD lesioned rats fed either normal diet or nonnutritive bulk diet (Figure 3; P < .05). Most the control rats showed normal 4- to 5-day estrous cycles (80% of the normal diet group, n = 10; 75% of the nonnutritive bulk diet group, n = 7), whereas only 38% for the normal diet group (n = 11) or 29% for the nonnutritive bulk diet group (n = 8) of the MePD-lesioned animals showed normal estrous cycles (Figure 3, A and F; P < .05). Representative examples of estrous cycles from each group are illustrated in Figure 3, B, C, G, and H. Cycle length was prolonged (Figure 3, D and I; P < .05) with an increase in metestrus and a decrease in diestrous phases evident in MePD-lesioned rats fed with normal diet or nonnutritive bulk diet (Figure 3, E and J; P < .05).

Bottom Line: In both dietary groups, MePD lesions resulted in an increase in socialization and a decrease in play fighting behavior.In conclusion, our results suggest the MePD regulates the timing of puberty via a novel mechanism independent of change in body weight and caloric intake.MePD glutamatergic systems advance the timing of puberty whereas local GABAergic activation results in a delay.

View Article: PubMed Central - PubMed

Affiliation: Division of Women's Health (X.F.L., M.H.L., B.P.H., Y.S.L., L.P., K.T.O.), Faculty of Life Sciences and Medicine, King's College London, Guy's Campus, London SE1 1UL, United Kingdom; and Henry Wellcome Laboratory for Integrative Neuroscience and Endocrinology (S.L.L.), University of Bristol, Bristol BS1 3NY, United Kingdom.

ABSTRACT
Obesity is the major risk factor for early puberty, but emerging evidence indicates other factors including psychosocial stress. One key brain region notable for its role in controlling calorie intake, stress, and behavior is the amygdala. Early studies involving amygdala lesions that included the medial nucleus advanced puberty in rats. More recently it was shown that a critical site for lesion-induced hyperphagia and obesity is the posterodorsal subnucleus of the medial amygdala (MePD), which may explain the advancement of puberty. Glutamatergic activity also increases in the MePD during puberty without a corresponding γ-aminobutyric acid (GABA)ergic change, suggesting an overall activation of this brain region. In the present study, we report that neurotoxic lesioning of the MePD advances puberty and increases weight gain in female rats fed a normal diet. However, MePD lesioned rats fed a 25% nonnutritive bulk diet also showed the dramatic advancement of puberty but without the increase in body weight. In both dietary groups, MePD lesions resulted in an increase in socialization and a decrease in play fighting behavior. Chronic GABAA receptor antagonism in the MePD from postnatal day 21 for 14 days also advanced puberty, increased socialization, and decreased play fighting without altering body weight, whereas glutamate receptor antagonism delayed puberty and decreased socialization without affecting play fighting. In conclusion, our results suggest the MePD regulates the timing of puberty via a novel mechanism independent of change in body weight and caloric intake. MePD glutamatergic systems advance the timing of puberty whereas local GABAergic activation results in a delay.

Show MeSH
Related in: MedlinePlus