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| Author(s): |
Naira da Silva Mansano
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) |
| Defense date: | 2022-09-12 |
| Examining board members: |
Renata Frazão;
Lucila Leico Kagohara Elias;
Davi José de Almeida Moraes;
Raphael Escorsim Szawka
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| Advisor: | Renata Frazão |
| Abstract | |
It is well known that nutritional status affects the reproduction, since an adequate amount of energy is necessary for puberty onset and fertility. The regulation of food intake and energy balance are modulated by leptin, which acts primarily on the arcuate nucleus (ARH), inhibiting the synthesis and secretion of orexigen neurotransmitters neuropeptide Y (NPY) and the Agouti-related peptide (AgRP) and stimulating the proopiomelanocortin (POMC). In ARH, there is also the population of kisspeptin neurons, which are considered the most important neuromodulator of gonadotrophin releasing hormone neurons (GnRH). Electrophysiological studies have shown that kisspeptins are able to directly excite POMC neurons and to indirect inhibit AgRP neurons. However, the neural mechanisms which control of food intake and reproduction have not yet been elucidated. In the present study we used neuroanatomic strategies, electrophysiological and genetically modified animals to determine the effects of fasting or food restriction (FR) on the estrous cycle and fertility. Adult females were individualized and maintained on an ad libitum diet (control) or fasted for 24 hours, or individualized and maintained on ad libitum chow or submitted to 60% FR A subgroup of animals was fed ad libitum after testing (fasting or FR). Females in the fasting and FR groups showed significant changes in body weight and estrous cycle, but without changes in reproduction. Fasting induced an increase in c-Fos expression in ARH, but without colocalization with kisspeptinergic neurons. In ARH, fasting induced the reduction of genes such as Kiss1, Cartp, Th and Pomc and increased the expression of Agrp and Npy genes. In addition, fasting suppressed the peak of luteinizing hormone (LH) secretion expected in the afternoon of proestrus and induced a significant increase in follicle stimulating hormone (FSH), without direct correlation with expected changes in the evaluation of the estrous cycle. To determine whether the observed changes would be sufficient to modulate the activity of kisspeptinergic neurons, we performed electrophysiological experiments. In general, no significant changes were observed in the activity of kisspeptinergic neurons in the anteroventral periventricular and anterior periventricular nucleus (AVPV/PeN). However, when we recorded inhibitory postsynaptic currents (sIPSC) in female ARH kisspeptinergic cells, we found that fasting decreased the frequency and amplitude, suggesting that fasting is sufficient to modulate the GABAergic transmission that acts on ARH kisspeptinergic neurons of females. In addition, we also demonstrated that the administration of neuropeptide Y (NPY, 100nM) induces membrane potential hyperpolarization only of ARH kisspeptinergic neurons, this effect being blocked by GABAergic, glutamatergic receptor antagonists. Our findings suggest that ARH kisspeptinergic neurons compose the neural pathway through which changes in energy expenditure are transmitted to the hypothalamic-pituitary-gonadal axis. (AU) | |
| FAPESP's process: | 17/22189-9 - Does the factors that change food intake modulate the activity of Kiss1 neurons? |
| Grantee: | Naira da Silva Mansano |
| Support Opportunities: | Scholarships in Brazil - Doctorate |