Salmon calcitonin distributes into the arcuate nucleus to a subset of NPY neurons in mice
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Salmon calcitonin distributes into the arcuate nucleus to a subset of NPY neurons in mice. / Zakariassen, Hannah Louise; John, Linu Mary; Lykkesfeldt, Jens; Raun, Kirsten; Glendorf, Tine; Schaffer, Lauge; Lundh, Sofia; Secher, Anna; Lutz, Thomas Alexander; Le Foll, Christelle.
In: Neuropharmacology, Vol. 167, 107987, 2020.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Salmon calcitonin distributes into the arcuate nucleus to a subset of NPY neurons in mice
AU - Zakariassen, Hannah Louise
AU - John, Linu Mary
AU - Lykkesfeldt, Jens
AU - Raun, Kirsten
AU - Glendorf, Tine
AU - Schaffer, Lauge
AU - Lundh, Sofia
AU - Secher, Anna
AU - Lutz, Thomas Alexander
AU - Le Foll, Christelle
PY - 2020
Y1 - 2020
N2 - The amylin receptor (AMY) and calcitonin receptor (CTR) agonists induce acute suppression of food intake in rodents by binding to receptors in the area postrema (AP) and potentially by targeting arcuate (ARC) neurons directly. Salmon calcitonin (sCT) induces more potent, longer lasting anorectic effects compared to amylin. We thus aimed to investigate whether AMY/CTR agonists target key neuronal populations in the ARC, and whether differing brain distribution patterns could mediate the observed differences in efficacy with sCT and amylin treatment. Brains were examined by whole brain 3D imaging and confocal microscopy following subcutaneous administration of fluorescently labelled peptides to mice. We found that sCT, but not amylin, internalizes into a subset of ARC NPY neurons, along with an unknown subset of ARC, AP and dorsal vagal motor nucleus cells. ARC POMC neurons were not targeted. Furthermore, amylin and sCT displayed similar distribution patterns binding to receptors in the AP, the organum vasculosum of the lamina terminalis (OVLT) and the ARC. Amylin distributed within the median eminence with only specs of sCT being present in this region, however amylin was only detectable 10 minutes after injection while sCT displayed a residence time of up to 2 hours post injection. We conclude that AMY/CTR agonists bind to receptors in a subset of ARC NPY neurons and in circumventricular organs. Furthermore, the more sustained and greater anorectic efficacy of sCT compared to rat amylin is not attributable to differences in brain distribution patterns but may more likely be explained by greater potency at both the CTR and AMY.
AB - The amylin receptor (AMY) and calcitonin receptor (CTR) agonists induce acute suppression of food intake in rodents by binding to receptors in the area postrema (AP) and potentially by targeting arcuate (ARC) neurons directly. Salmon calcitonin (sCT) induces more potent, longer lasting anorectic effects compared to amylin. We thus aimed to investigate whether AMY/CTR agonists target key neuronal populations in the ARC, and whether differing brain distribution patterns could mediate the observed differences in efficacy with sCT and amylin treatment. Brains were examined by whole brain 3D imaging and confocal microscopy following subcutaneous administration of fluorescently labelled peptides to mice. We found that sCT, but not amylin, internalizes into a subset of ARC NPY neurons, along with an unknown subset of ARC, AP and dorsal vagal motor nucleus cells. ARC POMC neurons were not targeted. Furthermore, amylin and sCT displayed similar distribution patterns binding to receptors in the AP, the organum vasculosum of the lamina terminalis (OVLT) and the ARC. Amylin distributed within the median eminence with only specs of sCT being present in this region, however amylin was only detectable 10 minutes after injection while sCT displayed a residence time of up to 2 hours post injection. We conclude that AMY/CTR agonists bind to receptors in a subset of ARC NPY neurons and in circumventricular organs. Furthermore, the more sustained and greater anorectic efficacy of sCT compared to rat amylin is not attributable to differences in brain distribution patterns but may more likely be explained by greater potency at both the CTR and AMY.
KW - Agonist
KW - Amylin
KW - Area postrema
KW - NPY
KW - Whole-brain 3D imaging
U2 - 10.1016/j.neuropharm.2020.107987
DO - 10.1016/j.neuropharm.2020.107987
M3 - Journal article
C2 - 32035146
AN - SCOPUS:85079217824
VL - 167
JO - Neuropharmacology
JF - Neuropharmacology
SN - 0028-3908
M1 - 107987
ER -
ID: 236714465