Chemogenetic Suppression of GnRH Neurons during Pubertal Development Can Alter Adult GnRH Neuron Firing Rate and Reproductive Parameters in Female Mice
| Autor: | R. Anthony DeFazio, Eden A. Dulka, Suzanne M. Moenter |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_specialty
endocrine system medicine.drug_class chemogenetic Neuronal Excitability Biology Inhibitory postsynaptic potential Gonadotropin-Releasing Hormone Mice Anterior pituitary neural activity Pregnancy Internal medicine medicine Premovement neuronal activity neuroendocrine Animals Sexual Maturation development GnRH Neuron Neurons General Neuroscience Reproduction General Medicine Androgen Polycystic ovary medicine.anatomical_structure Endocrinology nervous system Prenatal Exposure Delayed Effects Female Neuron Luteinizing hormone infertility hormones hormone substitutes and hormone antagonists Research Article: New Research |
| Zdroj: | eNeuro |
| ISSN: | 2373-2822 |
| Popis: | Gonadotropin-releasing hormone (GnRH) neurons control anterior pituitary, and thereby gonadal, function. GnRH neurons are active before outward indicators of puberty appear. Prenatal androgen (PNA) exposure mimics reproductive dysfunction of the common fertility disorder polycystic ovary syndrome (PCOS) and reduces prepubertal GnRH neuron activity. Early neuron activity can play a critical role in establishing circuitry and adult function. We tested the hypothesis that changing prepubertal GnRH neuron activity programs adult GnRH neuron activity and reproduction independent of androgen exposure in female mice. Activating (3Dq) or inhibitory (4Di) designer receptors exclusively activated by designer drugs (DREADDs) were targeted to GnRH neurons using Cre-lox technology. In control studies, the DREADD ligand clozapine n-oxide (CNO) produced the expected changes in GnRH neuron activityin vitroand luteinizing hormone (LH) releasein vivo. CNO was administered to control or PNA mice between two and three weeks of age, when GnRH neuron firing rate is reduced in PNA mice. In controls, reducing prepubertal GnRH neuron activity with 4Di increased adult GnRH neuron firing rate and days in diestrus but did not change puberty onset or GABA transmission to these cells. In contrast, activating GnRH neurons had no effect on reproductive parameters or firing rate and did not rescue reproductive phenotypes in PNA mice. These studies support the hypothesis that prepubertal neuronal activity sculpts elements of the adult reproductive neuroendocrine axis and cyclicity but indicate that other PNA-induced programming actions are required for full reproductive phenotypes and/or that compensatory mechanisms overcome activity-mediated changes to mitigate reproductive changes in adults. |
| Databáze: | OpenAIRE |
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