Summary of ssbd-repos-000297

Name
URL
DOI

Title
Fiber photometry traces of the kisspeptin neurons in the arcuate nucleus of the hypothalamus in young and aging mice
Description

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.

Submited Date
2023-04-25
Release Date
2023-04-26
Updated Date
-
License
Funding information
-
File formats
CSV files
Data size
16.1 GB

Organism
Mus musculus
Strain
C57BL/6j
Cell Line
n/a
Genes
-
Proteins
-

GO Molecular Function (MF)
n/a
GO Biological Process (BP)
reproductive functions; pulsatile activities for secretion of gonadotrophin
GO Cellular Component (CC)
n/a
Study Type
neural activity; Ca2+ imaging
Imaging Methods
fiber photometory with GCaMP6s

Method Summary

See detail in Dynamics of Pulsatile Activities of Arcuate Kisspeptin Neurons in Aging Female Mice. Goto T et al. (2022), BioRxiv

Related paper(s)

Teppei Goto, Mitsue Hagihara, Kazunari Miyamichi (2023/01/01), Dynamics of Pulsatile Activities of Arcuate Kisspeptin Neurons in Aging Female Mice, bioRxiv, 2022.08.08.503241

Published in 2023/01/01

(Abstract) 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.Significance Statement The transition to reproductive senescence significantly impacts the quality of life of women, but the underlying neural mechanisms remain poorly characterized. Goto and Miyamichi establish long-term (from the reproductive to acyclic phase) chronic imaging of the central pacemaker activities of reproductive functions by fiber photometry in female mice. In particular, they focus on kisspeptin neurons in the arcuate nucleus of the hypothalamus. Their data reveal that during the transition to reproductive senescence, the pulsatile activities of kisspeptin neurons show unexpected robustness in terms of frequency, but a tendency for the intensity to decline. Their findings exhibit the power of direct chronic visualization of hormonal regulators in the brain, which is generally applicable to facilitate studies of aging-associated malfunctions in neuroendocrine systems.Competing Interest StatementThe authors have declared no competing interest.
Related paper(s)

Teppei Goto, Mitsue Hagihara, Kazunari Miyamichi (2023) Dynamics of pulsatile activities of arcuate kisspeptin neurons in aging female mice., eLife, Volume 12

Published in May 24, 2023 (Electronic publication in May 24, 2023, midnight )

(Abstract) 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 (ARC(kiss)), 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 ARC(kiss) may be responsible for reproductive aging and menopause-related disorders. However, the activity dynamics of ARC(kiss) during the natural transition to reproductive senescence remain unclear. Herein, we introduce chronic in vivo Ca(2+) imaging of ARC(kiss) in female mice by fiber photometry to monitor the synchronous episodes of ARC(kiss) (SEs(kiss)), 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 SEs(kiss), vary depending on the stage of the estrus cycle. During the transition to reproductive senescence, the integrity of SEs(kiss) patterns, including the frequency and waveforms, remains mostly unchanged, whereas the intensities tend to decline. These data illuminate the temporal dynamics of ARC(kiss) 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.

Contact(s)
Kazunari Miyamichi
Organization(s)
RIKEN , Center for Biosystems Dynamics Research , Lab for comparative connectomics
Image Data Contributors
Teppei Goto
Quantitative Data Contributors
Teppei Goto

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