Krajewski-Hall SJ, Blackmore EM, McMinn JR, McMullen NT, Rance NE (2017) Increased core temperature following ablation of neurokinin 3 receptor-expressing neurons in the mouse median preoptic nucleus and adjacent preoptic area (MnPO/POA). Neuroscience 2017 Abstracts 414.02 / PP19. Society for Neuroscience, Washington, DC.
Summary: We have previously proposed that KNDy neurons play a role in the generation of hot ﬂushes via neurokinin 3 receptor (NK3R) signaling in the preoptic hypothalamus. This hypothesis is strongly supported by recent clinical studies showing that the number and severity of hot ﬂushes is reduced by treatment with NK3R antagonists. To determine if preoptic NK3R neurons modulate thermoregulation in the mouse, we selectively ablated them using injections of saporin conjugated to a NK3R agonist (NK3-SAP). NK3-SAP was stereotaxically injected into Tacr3-EGFP mice to target the MnPO/POA. Controls received injections of BLANK-SAP. The mice were ovariectomized (OVX) and a telemetry probe was implanted i.p. to measure core temperature (TCORE) and activity. Skin temperature (TSKIN) was monitored using a temperature data-logger attached to the surface of the tail. In experiment 1, circadian temperature rhythms were monitored over a 3 day period in mice housed in their home cages (12 light:12 dark). In experiment 2, mice were exposed to three temperatures, 18, 28 and 35oC, in an environmental chamber. Mice were then implanted s.c. with estradiol (E2) capsules and the experiments repeated. We veriﬁed by immunohistochemistry and quantitative microscopy that approximately 80% of the EGFP-NK3R neurons in the MnPO were ablated using NK3-SAP. Ablation of NK3R neurons signiﬁcantly elevated TCORE during the light phase in both OVX and OVX + E2 mice (OVX: BLANK-SAP, 36.7 + 0.1 vs NK3-SAP 37.4 + 0.1; OVX+E2: Blank-SAP 36.1 + 0.1 vs NK3-SAP 36.8 + 0.1). NK3-SAP injections had no signiﬁcant eﬀect on TCORE during the dark phase. Ablation of NK3R neurons also increased TCORE during the light phase in mice exposed to 18oC and 28oC. All mice exhibited hyperthermia at 35oC. In contrast, ablation of NK3R neurons in the MnPO/POA had no eﬀect on TSKIN or activity regardless of experimental treatment. These data suggest that NK3R neurons in the MnPO/POA participate in the thermoregulatory axis by promoting heat loss during the day and provide further insight into the CNS thermoregulatory pathways that may be activated during the generation of hot ﬂushes.
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