Glutamatergic Neurokinin 3 Receptor Neurons in the Median Preoptic Nucleus Modulate Heat-Defense Pathways in Female Mice
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We have proposed that arcuate neurons coexpressing kisspeptin, neurokinin B, and dynorphin (KNDy neurons) contribute to hot flushes via projections to neurokinin 3 receptor (NK3R)-expressing neurons in the median preoptic nucleus (MnPO). To characterize the thermoregulatory role of MnPO NK3R neurons in female mice, we ablated these neurons using injections of saporin toxin conjugated to a selective NK3R agonist. Loss of MnPO NK3R neurons increased the core temperature (TCORE) during the light phase, with the frequency distributions indicating a regulated shift in the balance point. The increase in TCORE in the ablated mice occurred despite changes in the ambient temperature and regardless of estrogen status. We next determined whether an acute increase in ambient temperature or higher TCORE would induce Fos in preoptic enhanced green fluorescent protein (EGFP)-immunoreactive neurons in Tacr3-EGFP mice. Fos activation was increased in the MnPO but no induction of Fos was found in NK3R (EGFP-immunoreactive) neurons. Thus, MnPO NK3R neurons are not activated by warm thermosensors in the skin or viscera and are not warm-sensitive neurons. Finally, RNAscope was used to determine whether Tacr3 (NK3R) mRNA was coexpressed with vesicular glutamate transporter 2 or vesicular γ-aminobutyric acid (GABA) transporter mRNA, markers of glutamatergic and GABAergic neurotransmission, respectively. In the MnPO, 94% of NK3R neurons were glutamatergic, but in the adjacent medial preoptic area, 97% of NK3R neurons were GABAergic. Thus, NK3R neurons in the MnPO are glutamatergic and play a role in reducing TCORE but are not activated by warm thermal stimuli (internal or external). These findings suggest that KNDy neurons modulate thermosensory pathways for heat defense indirectly via a subpopulation of glutamatergic MnPO neurons that express NK3R.
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Ablation of neurokinin 3 receptor-expressing neurons did not prevent the thermoregulatory effects of estradiol.
“However, the ablation of neurokinin 3 receptor-expressing neurons did not prevent the thermoregulatory effects of estradiol, indicating that they are not essential for estrogen’s thermoregulatory effect [170].”
From Temperature regulation in women: Effects of the menstrual cycle (2020) · cites this paper as [170]
Neurokinin 3 receptor-expressing neurons are not essential for estrogen's thermoregulatory effect.
“However, the ablation of neurokinin 3 receptor-expressing neurons did not prevent the thermoregulatory effects of estradiol, indicating that they are not essential for estrogen’s thermoregulatory effect [170].”
From Temperature regulation in women: Effects of the menstrual cycle (2020) · cites this paper as [170]
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- Authors
- Krajewski-Hall, S. J., Miranda Dos Santos, F., McMullen, N. T., Blackmore, E. M., & Rance, N. E.
- Affiliations
- Department of Pathology, University of Arizona College of Medicine, Tucson, Arizona
- University of Arizona (US)
- Corresponding author
- Rance, Naomi E
- ORCID
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2019-02-07
- Volume
- 160
- Issue
- 4
- Pages
- 803-816
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- PMC
- PMC6424091
- OpenAlex
- W2912192285
- Cited by
- 42
- References
- 72
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 5 · 2023: 9 · 2022: 3 · 2021: 8 · 2020: 7 · 2019: 1
- FWCI
- 4.54
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Endocrinology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01 AG047887)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- neurokinin-3 receptor, median preoptic nucleus, thermoregulation, kisspeptin, neurokinin B, dynorphin, KNDy neurons, glutamatergic neurons, GABAergic neurons, core body temperature, TACR3, female mice, hot flashes
- MeSH terms
- Animals, Body Temperature Regulation, Dynorphins, Female, Hot Temperature, Neurons, Preoptic Area, Neurokinin B, Proto-Oncogene Proteins c-fos, Receptors, Neurokinin-3, Glutamic Acid, Hot Flashes, Mice, Kisspeptins
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