Fasting Modulates GABAergic Synaptic Transmission to Arcuate Kisspeptin Neurons in Female Mice

Author:

Mansano Naira da Silva1ORCID,Vieira Henrique Rodrigues1ORCID,Araujo-Lopes Roberta2,Szawka Raphael Escorsim2ORCID,Donato Jose3ORCID,Frazao Renata1ORCID

Affiliation:

1. Universidade de Sao Paulo, Instituto de Ciencias Biomedicas, Departamento de Anatomia , São Paulo, SP 05508-000 , Brazil

2. Universidade Federal de Minas Gerais, Departamento de Fisiologia e Biofisica, Instituto de Ciencias Biologicas , Belo Horizonte, MG 31270-901 , Brazil

3. Universidade de Sao Paulo, Instituto de Ciencias Biomedicas, Departamento de Fisiologia e Biofísica , São Paulo, SP 05508-000 , Brazil

Abstract

Abstract It is well-established that the hypothalamic–pituitary–gonadal (HPG) axis is suppressed due to negative energy balance. However, less information is available on whether kisspeptin neuronal activity contributes to fasting-induced responses. In the present study, female and male mice were fasted for 24 hours or provided food ad libitum (fed group) to determine whether acute fasting is sufficient to modulate kisspeptin neuronal activity. In female mice, fasting attenuated luteinizing hormone (LH) and prolactin (PRL) serum levels and increased follicle-stimulating hormone levels compared with the fed group. In contrast, fasting did not affect gonadotropin or PRL secretion in male mice. By measuring genes related to LH pulse generation in micropunches obtained from the arcuate nucleus of the hypothalamus (ARH), we observed that fasting reduced Kiss1 mRNA levels in female and male mice. In contrast, Pdyn expression was upregulated only in fasted female mice, whereas no changes in the Tac2 mRNA levels were observed in both sexes. Interestingly, the frequency and amplitude of the GABAergic postsynaptic currents recorded from ARH kisspeptin neurons (ARHKisspeptin) were reduced in 24-hour fasted female mice but not in males. Additionally, neuropeptide Y induced a hyperpolarization in the resting membrane potential of ARHKisspeptin neurons of fed female mice but not in males. Thus, the response of ARHKisspeptin neurons to fasting is sexually dependent with a female bias, associated with changes in gonadotropins and PRL secretion. Our findings suggest that GABAergic transmission to ARHKisspeptin neurons modulates the activity of the HPG axis during situations of negative energy balance.

Funder

São Paulo Research Foundation

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Conselho Nacional de Desenvolvimento Cientifico e Tecnologico

Publisher

The Endocrine Society

Subject

Endocrinology

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