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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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Coronal sections through the rat brain at the level of the MePD showing its spatial relationship with the surrounding nuclei and ibotenate lesion resulting in specific neuronal cell loss. A, Section without staining showing the lesion area localized to the MePD. B, Schematic representation of site of lesion in the MePD (black filled) adapted from the rat brain atlas (39). C, Representative example of a coronal brain section stained with cresyl violet illustrating substantial neuron loss in the MePD after ibotenic acid lesioning. The dotted line indicates the approximate border of MePD. E, Representative photomicrograph from a MePD sham-lesioned rat. D and F, Magnified images of the areas enclosed by the squares in panels C and E, respectively, and illustrating the significant neuron loss to the MePD (D). opt, optic track.
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Figure 1: Coronal sections through the rat brain at the level of the MePD showing its spatial relationship with the surrounding nuclei and ibotenate lesion resulting in specific neuronal cell loss. A, Section without staining showing the lesion area localized to the MePD. B, Schematic representation of site of lesion in the MePD (black filled) adapted from the rat brain atlas (39). C, Representative example of a coronal brain section stained with cresyl violet illustrating substantial neuron loss in the MePD after ibotenic acid lesioning. The dotted line indicates the approximate border of MePD. E, Representative photomicrograph from a MePD sham-lesioned rat. D and F, Magnified images of the areas enclosed by the squares in panels C and E, respectively, and illustrating the significant neuron loss to the MePD (D). opt, optic track.

Mentions: The extent and location of the lesions were confirmed by microscopic histological inspection, using cresyl-violet staining. The presence of extensive neuronal loss within the MePD was used as parameters to determine the existence of significant lesions. Only bilateral lesions that destroyed the MePD while leaving surrounding brain tissue largely intact were included in the study (Figure 1, A, C, and D). Animals were excluded from the analysis as a result of unsuccessful lesioning, unilateral damage, or damage extending outside the MePD. Of the 28 rats that underwent neurotoxic lesion surgery, 19 were verified with correct bilateral lesions in the MePD and were included in the analysis. The remaining nine were excluded. Of the 19 animals with correct lesions, eight were fed with the nonnutritive bulk diet and 11 with a standard diet. The sham lesion group contained seven fed with nonnutritive bulk food and 10 with a normal diet. All vehicle-injected rats sustained no obvious damage to the MePD (Figure 1, E and F).


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)

Coronal sections through the rat brain at the level of the MePD showing its spatial relationship with the surrounding nuclei and ibotenate lesion resulting in specific neuronal cell loss. A, Section without staining showing the lesion area localized to the MePD. B, Schematic representation of site of lesion in the MePD (black filled) adapted from the rat brain atlas (39). C, Representative example of a coronal brain section stained with cresyl violet illustrating substantial neuron loss in the MePD after ibotenic acid lesioning. The dotted line indicates the approximate border of MePD. E, Representative photomicrograph from a MePD sham-lesioned rat. D and F, Magnified images of the areas enclosed by the squares in panels C and E, respectively, and illustrating the significant neuron loss to the MePD (D). opt, optic track.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4588820&req=5

Figure 1: Coronal sections through the rat brain at the level of the MePD showing its spatial relationship with the surrounding nuclei and ibotenate lesion resulting in specific neuronal cell loss. A, Section without staining showing the lesion area localized to the MePD. B, Schematic representation of site of lesion in the MePD (black filled) adapted from the rat brain atlas (39). C, Representative example of a coronal brain section stained with cresyl violet illustrating substantial neuron loss in the MePD after ibotenic acid lesioning. The dotted line indicates the approximate border of MePD. E, Representative photomicrograph from a MePD sham-lesioned rat. D and F, Magnified images of the areas enclosed by the squares in panels C and E, respectively, and illustrating the significant neuron loss to the MePD (D). opt, optic track.
Mentions: The extent and location of the lesions were confirmed by microscopic histological inspection, using cresyl-violet staining. The presence of extensive neuronal loss within the MePD was used as parameters to determine the existence of significant lesions. Only bilateral lesions that destroyed the MePD while leaving surrounding brain tissue largely intact were included in the study (Figure 1, A, C, and D). Animals were excluded from the analysis as a result of unsuccessful lesioning, unilateral damage, or damage extending outside the MePD. Of the 28 rats that underwent neurotoxic lesion surgery, 19 were verified with correct bilateral lesions in the MePD and were included in the analysis. The remaining nine were excluded. Of the 19 animals with correct lesions, eight were fed with the nonnutritive bulk diet and 11 with a standard diet. The sham lesion group contained seven fed with nonnutritive bulk food and 10 with a normal diet. All vehicle-injected rats sustained no obvious damage to the MePD (Figure 1, E and F).

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