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Habenular kisspeptin modulates fear in the zebrafish.
Ogawa S, Nathan FM, Parhar IS (2014) Habenular kisspeptin modulates fear in the zebrafish. Proc Natl Acad Sci U S A 111(10):3841-3846. doi: 10.1073/pnas.1314184111
Summary: The peptide kisspeptin can be found in several areas of the brain, but its role in regions other than the hypothalamus has not been studied. Zebrafish express kiss1 mRNA which is a conserved ortholog of the mammalian KISSI/KissI making zebrafish a viable model for investigating the role of kisspeptin in various brain systems. Animals received 1 μg of the custom conjugate kiss-SAP (see NK3-SAP, Cat. #IT-63) via an intracranial injection. Blank-SAP (Cat. #IT-21) was used as a control. Reducing Kiss1 immunoreactivity in the habenula and the raphe reduced an invoked fear response, indicating a role for kisspeptin in fear inhibition.
Related Products: Blank-SAP (Cat. #IT-21), NKB-SAP (Cat. #IT-63), Custom Conjugates
Ablation of arcuate KNDy neurons amplifies the LH surge in steroid-primed, ovariectomized rats.
Krajewski-Hall SJ, Mittelman-Smith, Mcmullen NT, Rance NE (2013) Ablation of arcuate KNDy neurons amplifies the LH surge in steroid-primed, ovariectomized rats. Neuroscience 2013 Abstracts 274.01. Society for Neuroscience, San Diego, CA.
Summary: KNDy (kisspeptin, neurokinin B and dynorphin) neurons in the arcuate nucleus play an important role in the reproductive axis. We have developed a method to selectively ablate KNDy neurons in the rat using NK3-SAP, a neurokinin 3 receptor agonist conjugated to saporin (Mittelman-Smith, Endocrinology 2012). Ablation of KNDy neurons results in cessation of estrous cycles, ovarian atrophy, a decrease in tonic LH secretion and loss of the rise of serum LH after ovariectomy. Given these profound effects, we tested if we could induce an LH surge in KNDy-ablated rats using a well-established steroid replacement regimen. Rats were maintained on a 14:10 light cycle (lights on at 0500). Using stereotactic surgery, NK3-SAP or Blank-SAP was injected in the arcuate nucleus and rats were allowed to recover for one month before ovariectomy. Seven days after ovariectomy they were implanted with silastic capsules containing 17β-estradiol. Two days later, they were implanted with progesterone capsules (~0830h). Rats were sacrificed in the afternoon at a time previously shown to exhibit peak LH surge levels (~1600h) and the brains were processed for immunohistochemistry. Ablation of KNDy neurons was verified by near complete loss of NKB-immunoreactive neurons in the arcuate nucleus in NK3-SAP rats. At 0830h, tonic levels of serum LH were significantly lower in KNDy ablated rats, consistent with our previous studies. Unexpectedly, the surge in serum LH at 1600h was more than 3-fold higher in NK3-SAP-treated rats compared to Blank-SAP controls (53.5 + 16.5 ng/ml vs 16.5 + 2.1 ng/ml, respectively). To determine if this change was associated with increased activation of GnRH neurons, dual-labeled GnRH-fos immunocytochemistry was performed in rostral hypothalamic sections. There was no significant difference in the total number of GnRH cells counted in 4 matched sections (NK3-SAP, 85.8 + 9.8 vs Blank-SAP, 84.9 + 4.6) or in the percentage of GnRH cells that were activated, as measured by GnRH-fos coexpression (NK3-SAP, 22.4 + 1.8% vs Blank-SAP, 16.6 + 4.9%). In addition, there was no difference between NK3-SAP and Blank-SAP controls in the number of fos-ir cells counted in the AVPV. These data indicate that arcuate KNDy neurons are not required for the induction of an LH surge. The marked increase in the LH surge in KNDy-ablated rats, however, suggests that KNDy neurons are important for regulating the magnitude of the surge.
Related Products: NKB-SAP (Cat. #IT-63)
Time course study of targeted ablation of KNDy neurons, but not tyrosine-hydroxylase neurons, in the rat arcuate nucleus using a neurokinin b-saporin.
Helena CV, Kalil B, Anselmo-Franci JA, Bertram R (2013) Time course study of targeted ablation of KNDy neurons, but not tyrosine-hydroxylase neurons, in the rat arcuate nucleus using a neurokinin b-saporin. Endocr Rev 34:OR47-5. 95th Annual Meetin and Expo, San Francisco. doi: 10.1093/edrv/34.supp.1
Summary: Ovariectomized rats were given bilateral injections of NK3-SAP (Cat. #IT-63) into the arcuate nucleus for a time course study of KNDy neuron loss. Blank-SAP (Cat. #IT-21) was used as a control.
Related Products: NKB-SAP (Cat. #IT-63), Blank-SAP (Cat. #IT-21)
Role for kisspeptin/neurokinin B/dynorphin (KNDy) neurons in cutaneous vasodilatation and the estrogen modulation of body temperature.
Mittelman-Smith MA, Williams H, Krajewski-Hall SJ, McMullen NT, Rance NE (2012) Role for kisspeptin/neurokinin B/dynorphin (KNDy) neurons in cutaneous vasodilatation and the estrogen modulation of body temperature. Proc Natl Acad Sci U S A 109(48):19846-19851. doi: 10.1073/pnas.1211517109
Summary: Menopause is marked by estrogen withdrawal, and also by hot flushes. Given the fact that hypothalamic levels of kisspeptin/neurokinin B/dynorphin (KNDy) neurons are significantly altered in menopause, the authors investigated whether these neurons are involved in the generation of flushes. Rats received bilateral injections of NK3-SAP (Cat. #IT-63) into the arcuate nucleus – a total of 40 ng. Blank-SAP (Cat. #IT-21) was used as control. The data indicate that KNDy neurons promote cutaneous vasodilation, and play a role in 17β-estradiol modulation of body temperature, supporting the hypothesis that these neurons could play a role in the generation of hot flushes.
Related Products: NKB-SAP (Cat. #IT-63), Blank-SAP (Cat. #IT-21)
A role for kisspeptin/neurokinin B/dynorphin (KNDy) neurons in the regulation of estrous cycles and the estrogen modulation of body temperature.
Krajewski-Hall SJ, Mittelman-Smith MA, Williams H, Lafrance KJ, Mcmullen NT, Rance NE (2012) A role for kisspeptin/neurokinin B/dynorphin (KNDy) neurons in the regulation of estrous cycles and the estrogen modulation of body temperature. Neuroscience 2012 Abstracts 585.02. Society for Neuroscience, New Orleans, LA.
Summary: We have recently described a method to selectively ablate kisspeptin/neurokinin B/dynorphin (KNDy) neurons using stereotaxic injections of NK3-SAP, a neurokinin 3 receptor agonist conjugated to saporin (Mittelman-Smith, Endocrinology, 2012). These studies revealed a critical role for arcuate KNDy neurons in tonic gonadotropin secretion, the rise in serum LH after ovariectomy and estrogen modulation of body weight. Here we determine the effects of KNDy neuron ablation on estrous cycles and the estradiol modulation of body temperature. In the first study, stereotaxic injections of NK3-SAP or Blank-SAP were made in the arcuate nucleus of ovary-intact, adult female rats. Rats with nearly complete KNDy-neuron ablation (verified by NKB immunohistochemistry) exhibited constant diestrus and ovarian atrophy, confirming the importance of these neurons in reproductive regulation. In a second experiment, we evaluated the effects of KNDy neuron ablation on the thermoregulatory axis in rats that were ovariectomized (OVX) and then treated with 17β-estradiol (E2). Tail skin temperatures (TSKIN) and core temperatures (TCORE) were recorded in rats throughout the light/dark cycle and during exposure to different ambient temperatures (TAMBIENT) in an environmental chamber. Notably, the average TSKIN of KNDy-ablated rats was consistently lower than control rats, indicative of lower levels of cutaneous vasodilatation. Moreover, KNDy neuron ablation blocked the reduction of TSKIN by E2 that occurred during the light phase in the environmental chamber, but did not affect the E2 suppression of TSKIN during the dark phase. At a high TAMBIENT of 33 C, the mean TCORE of OVX control rats increased to 39.0 C, and was reduced by E2 replacement. In contrast, at this high TAMBIENT, the average TCORE of OVX, KNDy-ablated rats was lower than OVX control rats, and TCORE was not altered by E2 replacement. Because KNDy neurons exhibit dramatic changes in morphology and gene expression in postmenopausal women, we have hypothesized these neurons contribute to the generation of hot flushes. These studies support this hypothesis by providing the first evidence that KNDy neurons participate in the E2 modulation of body temperature and promote cutaneous vasodilatation, one of the cardinal signs of a hot flush.
Related Products: NKB-SAP (Cat. #IT-63), Blank-SAP (Cat. #IT-21)
Arcuate kisspeptin/neurokinin b/dynorphin (KNDy) neurons mediate the estrogen suppression of gonadotropin secretion and body weight.
Mittelman-Smith MA, Williams H, Krajewski-Hall SJ, Lai J, Ciofi P, McMullen NT, Rance NE ( 2012 ) Arcuate kisspeptin/neurokinin b/dynorphin (KNDy) neurons mediate the estrogen suppression of gonadotropin secretion and body weight. Endocrinology 153(6):2800-2812 . doi: 10.1210/en.2012-1045
Related Products: NKB-SAP (Cat. #IT-63), Blank-SAP (Cat. #IT-21)
Featured Article: Use of a novel saporin conjugate (NK3-SAP) to study the function of neurokinin 3 receptor (NK3r)-expressing kisspeptin/neurokinin B/dynorphin (KNDy) neurons in the rat arcuate nucleus
Rance NE, Mittelman-Smith MA, Krajewski-Hall SJ (2012) Featured Article: Use of a novel saporin conjugate (NK3-SAP) to study the function of neurokinin 3 receptor (NK3r)-expressing kisspeptin/neurokinin B/dynorphin (KNDy) neurons in the rat arcuate nucleus. Targeting Trends 13(2)
Related Products: NKB-SAP (Cat. #IT-63), Blank-SAP (Cat. #IT-21)
Read the featured article in Targeting Trends.
See Also:
Bronchoconstrictor effect of the tachykinin NK₃-receptor agonists [MePhe⁷]-neurokinin B and senktide in the isolated guinea pig lung
Corboz MR, Rivelli MA, Eckel SP (2010) Bronchoconstrictor effect of the tachykinin NK₃-receptor agonists [MePhe⁷]-neurokinin B and senktide in the isolated guinea pig lung. Exp Lung Res 36(9):509-521. doi: 10.3109/01902141003777582
Related Products: NKB-SAP (Cat. #IT-63)
Selective agonists for substance P and neurokinin receptors
Drapeau G, D’Orléans-Juste P, Dion S, Rhaleb NE, Rouissi NE, Regoli D (1987) Selective agonists for substance P and neurokinin receptors. Neuropeptides 10:43-54. doi: 10.1016/0143-4179(87)90088-6
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Specific agonists for neurokinin B receptors
Drapeau G, d’Orléans-Juste P, Dion S, Rhaleb NE, Regoli D (1987) Specific agonists for neurokinin B receptors. Eur J Pharmacol 136(3):401-403. doi: 10.1016/0014-2999(87)90313-x
Related Products: NKB-SAP (Cat. #IT-63)