Dynamics of pulsatile activities of arcuate kisspeptin neurons in aging female mice
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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.
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A perfect correlation exists between ARNKISS neuron SEs and LH pulses in all physiological and pathophysiological conditions examined to date.
“A perfect correlation exists between ARNKISS neuron SEs and LH pulses in all physiological and pathophysiological conditions examined to date7–11.”
From Brainstem noradrenergic modulation of the kisspeptin neuron GnRH pulse generator in mice (2025) · cites this paper as [10]
The Introduction (page unavailable) says ARCkiss synchronous episodes are well correlated with pulsatile LH secretion. It does not establish a perfect correlation across all physiological and pathophysiological conditions; the Discussion describes some relationships between episode intensity and LH pulses as consistent with, or potentially explanatory of, other findings. (LLM, conf=0.87)
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- Authors
- Goto, T., Hagihara, M., & Miyamichi, K.
- Affiliations
- RIKEN Center for Biosystems Dynamics Research (JP)
- Corresponding author
- Goto, Teppei
- Miyamichi, Kazunari
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2023-05-24
- Volume
- 12
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC10208635
- OpenAlex
- W4378072288
- Cited by
- 27
- References
- 51
- Citations by year
- 2026: 10 · 2025: 9 · 2024: 6 · 2023: 1 · 2022: 1
- FWCI
- 6.23
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Japan Society for the Promotion of Science (19K16270, 21K15194, 20K20589, 21H02587)
- RIKEN (Special Postdoctoral Researchers Program)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Keywords
- kisspeptin neurons, arcuate nucleus, reproductive aging, menopause, GnRH pulsatility, GnRH pulse generator, estrous cycle, calcium imaging, fiber photometry, neuroendocrine regulation, fertility loss
- MeSH terms
- Aging, Animals, Female, Gonadotropin-Releasing Hormone, Neurons, Reproduction, Mice, Kisspeptins
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