Sulfated cholecystokinin-8 activates phospho-mTOR immunoreactive neurons of the paraventricular nucleus in rats. Peptides 2011 Jan;32(1):65-70
Date
10/12/2010Pubmed ID
20933028Pubmed Central ID
PMC4040259DOI
10.1016/j.peptides.2010.09.025Scopus ID
2-s2.0-78650523345 (requires institutional sign-in at Scopus site) 12 CitationsAbstract
The serin/threonin-kinase, mammalian target of rapamycin (mTOR) was detected in the arcuate nucleus (ARC) and paraventricular nucleus of the hypothalamus (PVN) and suggested to play a role in the integration of satiety signals. Since cholecystokinin (CCK) plays a role in the short-term inhibition of food intake and induces c-Fos in PVN neurons, the aim was to determine whether intraperitoneally injected CCK-8S affects the neuronal activity in cells immunoreactive for phospho-mTOR in the PVN. Ad libitum fed male Sprague-Dawley rats received 6 or 10 μg/kg CCK-8S or 0.15M NaCl ip (n=4/group). The number of c-Fos-immunoreactive (ir) neurons was assessed in the PVN, ARC and in the nucleus of the solitary tract (NTS). CCK-8S increased the number of c-Fos-ir neurons in the PVN (6 μg: 103 ± 13 vs. 10 μg: 165 ± 14 neurons/section; p<0.05) compared to vehicle treated rats (4 ± 1, p<0.05), but not in the ARC. CCK-8S also dose-dependently increased the number of c-Fos neurons in the NTS. Staining for phospho-mTOR and c-Fos in the PVN showed a dose-dependent increase of activated phospho-mTOR neurons (17 ± 3 vs. 38 ± 2 neurons/section; p<0.05), while no activated phospho-mTOR neurons were observed in the vehicle group. Triple staining in the PVN showed activation of phospho-mTOR neurons co-localized with oxytocin, corresponding to 9.8 ± 3.6% and 19.5 ± 3.3% of oxytocin neurons respectively. Our observations indicate that peripheral CCK-8S activates phospho-mTOR neurons in the PVN and suggest that phospho-mTOR plays a role in the mediation of CCK-8S's anorexigenic effects.
Author List
Lembke V, Goebel M, Frommelt L, Inhoff T, Lommel R, Stengel A, Taché Y, Grötzinger C, Bannert N, Wiedenmann B, Klapp BF, Kobelt PMESH terms used to index this publication - Major topics in bold
AnimalsHypothalamus
Male
Neurons
Paraventricular Hypothalamic Nucleus
Rats
Rats, Sprague-Dawley
Sincalide
TOR Serine-Threonine Kinases