Dynamics of pulsatile activities of arcuate kisspeptin neurons in aging female mice

Reproductive senescence is broadly observed across mammalian females, including humans, eventually leading to a loss of fertility. The pulsatile secretion of gonadotropin-releasing hormone (GnRH), which is essential for gonad function, is primarily controlled by kisspeptin neurons in the hypothalami...

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Main Authors: Teppei Goto, Mitsue Hagihara, Kazunari Miyamichi
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2023-05-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/82533
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author Teppei Goto
Mitsue Hagihara
Kazunari Miyamichi
author_facet Teppei Goto
Mitsue Hagihara
Kazunari Miyamichi
author_sort Teppei Goto
collection DOAJ
description Reproductive senescence is broadly observed across mammalian females, including humans, eventually leading to a loss of fertility. The pulsatile secretion of gonadotropin-releasing hormone (GnRH), which is essential for gonad function, is primarily controlled by kisspeptin neurons in the hypothalamic arcuate nucleus (ARCkiss), the pulse generator of GnRH. The pulsatility of GnRH release, as assessed by the amount of circulating gonadotropin, is markedly reduced in aged animals, suggesting that the malfunctions of ARCkiss may be responsible for reproductive aging and menopause-related disorders. However, the activity dynamics of ARCkiss during the natural transition to reproductive senescence remain unclear. Herein, we introduce chronic in vivo Ca2+ imaging of ARCkiss in female mice by fiber photometry to monitor the synchronous episodes of ARCkiss (SEskiss), a known hallmark of GnRH pulse generator activity, from the fully reproductive to acyclic phase over 1 year. During the reproductive phase, we find that not only the frequency, but also the intensities and waveforms of individual SEskiss, vary depending on the stage of the estrus cycle. During the transition to reproductive senescence, the integrity of SEskiss patterns, including the frequency and waveforms, remains mostly unchanged, whereas the intensities tend to decline. These data illuminate the temporal dynamics of ARCkiss activities in aging female mice. More generally, our findings demonstrate the utility of fiber-photometry-based chronic imaging of neuroendocrine regulators in the brain to characterize aging-associated malfunction.
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spelling doaj.art-601fb0fe8f674b8bb4ebfcf4c0324f982023-05-24T15:24:51ZengeLife Sciences Publications LtdeLife2050-084X2023-05-011210.7554/eLife.82533Dynamics of pulsatile activities of arcuate kisspeptin neurons in aging female miceTeppei Goto0https://orcid.org/0000-0002-0081-3357Mitsue Hagihara1Kazunari Miyamichi2https://orcid.org/0000-0002-7807-8436Laboratory for Comparative Connectomics, RIKEN Center for Biosystems Dynamics Research, Kobe, JapanLaboratory for Comparative Connectomics, RIKEN Center for Biosystems Dynamics Research, Kobe, JapanLaboratory for Comparative Connectomics, RIKEN Center for Biosystems Dynamics Research, Kobe, JapanReproductive senescence is broadly observed across mammalian females, including humans, eventually leading to a loss of fertility. The pulsatile secretion of gonadotropin-releasing hormone (GnRH), which is essential for gonad function, is primarily controlled by kisspeptin neurons in the hypothalamic arcuate nucleus (ARCkiss), the pulse generator of GnRH. The pulsatility of GnRH release, as assessed by the amount of circulating gonadotropin, is markedly reduced in aged animals, suggesting that the malfunctions of ARCkiss may be responsible for reproductive aging and menopause-related disorders. However, the activity dynamics of ARCkiss during the natural transition to reproductive senescence remain unclear. Herein, we introduce chronic in vivo Ca2+ imaging of ARCkiss in female mice by fiber photometry to monitor the synchronous episodes of ARCkiss (SEskiss), a known hallmark of GnRH pulse generator activity, from the fully reproductive to acyclic phase over 1 year. During the reproductive phase, we find that not only the frequency, but also the intensities and waveforms of individual SEskiss, vary depending on the stage of the estrus cycle. During the transition to reproductive senescence, the integrity of SEskiss patterns, including the frequency and waveforms, remains mostly unchanged, whereas the intensities tend to decline. These data illuminate the temporal dynamics of ARCkiss activities in aging female mice. More generally, our findings demonstrate the utility of fiber-photometry-based chronic imaging of neuroendocrine regulators in the brain to characterize aging-associated malfunction.https://elifesciences.org/articles/82533kisspeptinFiber photometryagingmenopause
spellingShingle Teppei Goto
Mitsue Hagihara
Kazunari Miyamichi
Dynamics of pulsatile activities of arcuate kisspeptin neurons in aging female mice
eLife
kisspeptin
Fiber photometry
aging
menopause
title Dynamics of pulsatile activities of arcuate kisspeptin neurons in aging female mice
title_full Dynamics of pulsatile activities of arcuate kisspeptin neurons in aging female mice
title_fullStr Dynamics of pulsatile activities of arcuate kisspeptin neurons in aging female mice
title_full_unstemmed Dynamics of pulsatile activities of arcuate kisspeptin neurons in aging female mice
title_short Dynamics of pulsatile activities of arcuate kisspeptin neurons in aging female mice
title_sort dynamics of pulsatile activities of arcuate kisspeptin neurons in aging female mice
topic kisspeptin
Fiber photometry
aging
menopause
url https://elifesciences.org/articles/82533
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AT mitsuehagihara dynamicsofpulsatileactivitiesofarcuatekisspeptinneuronsinagingfemalemice
AT kazunarimiyamichi dynamicsofpulsatileactivitiesofarcuatekisspeptinneuronsinagingfemalemice