Kisspeptin Neuron-Specific and Self-Sustained Calcium Oscillation in the Hypothalamic Arcuate Nucleus of Neonatal Mice: Regulatory Factors of its Synchronization.
Neuroendocrinology
; 110(11-12): 1010-1027, 2020.
Article
em En
| MEDLINE
| ID: mdl-31935735
ABSTRACT
INTRODUCTION:
Synchronous and pulsatile neural activation of kisspeptin neurons in the arcuate nucleus (ARN) are important components of the gonadotropin-releasing hormone pulse generator, the final common pathway for central regulation of mammalian reproduction. However, whether ARN kisspeptin neurons can intrinsically generate self-sustained synchronous oscillations from the early neonatal period and how they are regulated remain unclear.OBJECTIVE:
This study aimed to examine the endogenous rhythmicity of ARN kisspeptin neurons and its neural regulation using a neonatal organotypic slice culture model.METHODS:
We monitored calcium (Ca2+) dynamics in real-time from individual ARN kisspeptin neurons in neonatal organotypic explant cultures of Kiss1-IRES-Cre mice transduced with genetically encoded Ca2+ indicators. Pharmacological approaches were employed to determine the regulations of kisspeptin neuron-specific Ca2+ oscillations. A chemogenetic approach was utilized to assess the contribution of ARN kisspeptin neurons to the population dynamics.RESULTS:
ARN kisspeptin neurons in neonatal organotypic cultures exhibited a robust synchronized Ca2+ oscillation with a period of approximately 3 min. Kisspeptin neuron-specific Ca2+ oscillations were dependent on voltage-gated sodium channels and regulated by endoplasmic reticulum-dependent Ca2+ homeostasis. Chemogenetic inhibition of kisspeptin neurons abolished synchronous Ca2+ oscillations, but the autocrine actions of the neuropeptides were marginally effective. Finally, neonatal ARN kisspeptin neurons were regulated by N-methyl-D-aspartate and gamma-aminobutyric acid receptor-mediated neurotransmission.CONCLUSION:
These data demonstrate that ARN kisspeptin neurons in organotypic cultures can generate synchronized and self-sustained Ca2+ oscillations. These oscillations controlled by multiple regulators within the ARN are a novel ultradian rhythm generator that is active during the early neonatal period.Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Núcleo Arqueado do Hipotálamo
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Sinalização do Cálcio
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Kisspeptinas
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Ritmo Ultradiano
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Neurônios
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Neuroendocrinology
Ano de publicação:
2020
Tipo de documento:
Article