Levels of Cocaine- and Amphetamine-Regulated Transcript in Vagal Afferents in the Mouse Are Unaltered in Response to Metabolic Challenges.
Cocaine- and amphetamine-regulated transcript (CART) is one of the most abundant neuropeptides in vagal afferents, including those involved in regulating feeding. Recent observations indicate that metabolic challenges dramatically alter the neuropeptidergic profile of CART-producing vagal afferents. Here, using confocal microscopy, we reassessed the distribution and regulation of CART(55-102) immunoreactivity in vagal afferents of the male mouse in response to metabolic challenges, including fasting and high-fat-diet feeding. Importantly, the perikarya and axons of vagal C-fibers were labeled using mice expressing channelrodhopsin-2 (ChR2-YFP) in Nav1.8-Cre-expressing neurons. In these mice, approximately 82% of the nodose ganglion neurons were labeled with ChR2-YFP. Furthermore, ChR2-YFP-labeled axons could easily be identified in the dorsovagal complex. CART(55-102) immunoreactivity was observed in 55% of the ChR2-YFP-labeled neurons in the nodose ganglion and 22% of the ChR2-YFP-labeled varicosities within the area postrema of fed, fasted, and obese mice. The distribution of positive profiles was also identical across the full range of CART staining in fed, fasted, and obese mice. In contrast to previous studies, fasting did not induce melanin-concentrating hormone (MCH) immunoreactivity in vagal afferents. Moreover, prepro-MCH mRNA was undetectable in the nodose ganglion of fasted mice. In summary, this study showed that the perikarya and central terminals of vagal afferents are invariably enriched in CART and devoid of MCH.
Division of Hypothalamic Research and Department of Internal Medicine, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, Texas 75390; Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Xuefeng
0000-0003-1666-850X
X
Yuan
Division of Hypothalamic Research and Department of Internal Medicine, The University of Texas Southwestern Medical Center , 5323 Harry Hines Blvd., Dallas, Texas 75390.
Ying
Y
Huang
Division of Hypothalamic Research and Department of Internal Medicine, The University of Texas Southwestern Medical Center , 5323 Harry Hines Blvd., Dallas, Texas 75390.
Sarita
0000-0001-6007-8019
S
Shah
Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China.
Hua
H
Wu
Division of Hypothalamic Research and Department of Internal Medicine, The University of Texas Southwestern Medical Center , 5323 Harry Hines Blvd., Dallas, Texas 75390.
Laurent
0000-0003-3609-7441
L
Gautron
D000818:Animals; D004435:Eating / Q000502:physiology*; D005215:Fasting / Q000502:physiology*; D041981:Gastrointestinal Tract / Q000294:innervation / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D007028:Hypothalamic Hormones / Q000378:metabolism; D008297:Male; D008543:Melanins / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D062559:NAV1.8 Voltage-Gated Sodium Channel / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009475:Neurons, Afferent / Q000378:metabolism* / Q000473:pathology; D009620:Nodose Ganglion / Q000378:metabolism / Q000473:pathology; D009765:Obesity / Q000378:metabolism* / Q000473:pathology; D010907:Pituitary Hormones / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011924:Rats, Zucker; D014630:Vagus Nerve / Q000378:metabolism* / Q000473:pathology; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
D007028:Hypothalamic Hormones; D008543:Melanins; D062559:NAV1.8 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D010907:Pituitary Hormones; D012333:RNA, Messenger; C568318:Scn10a protein, mouse; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; C019463:melanin-concentrating hormone
immunohistochemistry; metabolism; neuropeptide; vagus nerve