Neurokinin 3 receptor-expressing neurons in the median preoptic nucleus modulate heat-dissipation effectors in the female rat

Melinda A. Mittelman-Smith, Sally J. Krajewski-Hall, Nathaniel T. McMullen, Naomi E Rance

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Abstract

KNDy neurons facilitate tail skin vasodilation and modulate the effects of estradiol on thermoregulation. We hypothesize that KNDy neurons influence cutaneous vasodilation via projections to neurons in the median preoptic nucleus (MnPO) that express the neurokinin 3 receptor (NK<inf>3</inf>R). In support of this hypothesis, focal microinjections of senktide, an NK<inf>3</inf>R agonist, into the MnPO lowers core temperature (T<inf>CORE</inf>) in the female rat. To further study the role of MnPO NK<inf>3</inf>R neurons in thermoregulation, these neurons were specifically ablated using a conjugate of a selective NK<inf>3</inf>R agonist and saporin (NK<inf>3</inf>-SAP). NK<inf>3</inf>-SAP or blank-SAP (control) was injected into the MnPO/medial septum. Tail skin temperature (T<inf>SKIN</inf>) and T<inf>CORE</inf> were measured in ovariectomized rats exposed to 3 ambient temperatures (T<inf>AMBIENT</inf>) before and after estradiol-17β (E<inf>2</inf>) treatment. Before killing, we injected senktide (sc), monitored T<inf>CORE</inf> for 70 minutes, and harvested brains for Fos immunohistochemistry. Ablation of MnPO NK<inf>3</inf>R neurons lowered T<inf>SKIN</inf> at neutral and subneutral T<inf>AMBIENT</inf> regardless of E<inf>2</inf> treatment. However, ablation did not prevent the effects of E<inf>2</inf> on T<inf>CORE</inf> and T<inf>SKIN</inf>. In control rats, senktide injections induced hypothermia with numerous Fos-immunoreactive cells in the MnPO. In contrast, in NK<inf>3</inf>-SAP rats, senktide did not alter T<inf>CORE</inf> and minimal Fos-immunoreactive neurons were identified in the MnPO. These data show that NK<inf>3</inf>R neurons in the MnPO are required for the hypothermic effects of senktide but not for the E<inf>2</inf> modulation of thermoregulation. The lower T<inf>SKIN</inf> in NK<inf>3</inf>-SAP-injected rats suggests that MnPO NK<inf>3</inf>R neurons, like KNDy neurons, facilitate cutaneous vasodilation, an important heat-dissipation effector.

Original languageEnglish (US)
Pages (from-to)2552-2562
Number of pages11
JournalEndocrinology
Volume156
Issue number7
DOIs
StatePublished - Jul 1 2015

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Neurokinin-3 Receptors
Preoptic Area
Hot Temperature
Neurons
Skin Temperature
Tail
Body Temperature Regulation
Vasodilation
Skin
Temperature
Estradiol
Induced Hypothermia
Microinjections

ASJC Scopus subject areas

  • Endocrinology

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Neurokinin 3 receptor-expressing neurons in the median preoptic nucleus modulate heat-dissipation effectors in the female rat. / Mittelman-Smith, Melinda A.; Krajewski-Hall, Sally J.; McMullen, Nathaniel T.; Rance, Naomi E.

In: Endocrinology, Vol. 156, No. 7, 01.07.2015, p. 2552-2562.

Research output: Contribution to journalArticle

Mittelman-Smith, Melinda A. ; Krajewski-Hall, Sally J. ; McMullen, Nathaniel T. ; Rance, Naomi E. / Neurokinin 3 receptor-expressing neurons in the median preoptic nucleus modulate heat-dissipation effectors in the female rat. In: Endocrinology. 2015 ; Vol. 156, No. 7. pp. 2552-2562.
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abstract = "KNDy neurons facilitate tail skin vasodilation and modulate the effects of estradiol on thermoregulation. We hypothesize that KNDy neurons influence cutaneous vasodilation via projections to neurons in the median preoptic nucleus (MnPO) that express the neurokinin 3 receptor (NK3R). In support of this hypothesis, focal microinjections of senktide, an NK3R agonist, into the MnPO lowers core temperature (TCORE) in the female rat. To further study the role of MnPO NK3R neurons in thermoregulation, these neurons were specifically ablated using a conjugate of a selective NK3R agonist and saporin (NK3-SAP). NK3-SAP or blank-SAP (control) was injected into the MnPO/medial septum. Tail skin temperature (TSKIN) and TCORE were measured in ovariectomized rats exposed to 3 ambient temperatures (TAMBIENT) before and after estradiol-17β (E2) treatment. Before killing, we injected senktide (sc), monitored TCORE for 70 minutes, and harvested brains for Fos immunohistochemistry. Ablation of MnPO NK3R neurons lowered TSKIN at neutral and subneutral TAMBIENT regardless of E2 treatment. However, ablation did not prevent the effects of E2 on TCORE and TSKIN. In control rats, senktide injections induced hypothermia with numerous Fos-immunoreactive cells in the MnPO. In contrast, in NK3-SAP rats, senktide did not alter TCORE and minimal Fos-immunoreactive neurons were identified in the MnPO. These data show that NK3R neurons in the MnPO are required for the hypothermic effects of senktide but not for the E2 modulation of thermoregulation. The lower TSKIN in NK3-SAP-injected rats suggests that MnPO NK3R neurons, like KNDy neurons, facilitate cutaneous vasodilation, an important heat-dissipation effector.",
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