Abstract：
:Up to 80% of cancer patients are affected by the cancer anorexia-cachexia syndrome (CACS), which leads to excessive body weight loss, reduced treatment success and increased lethality. The area postrema/nucleus of the solitary tract (AP/NTS) region emerged as a central nervous key structure in this multi-factorial process. Neurons in this area are targeted by cytokines and signal to downstream sites involved in energy homeostasis. NTS neurons expressing prolactin-releasing peptide (PrRP) are implicated in the control of energy intake and hypothalamus-pituitary-adrenal (HPA) axis activation, which contributes to muscle wasting. To explore if brainstem PrRP neurons contribute to CACS, we selectively knocked down PrRP expression in the NTS of hepatoma tumor-bearing rats by an AAV/shRNA gene silencing approach. PrRP knockdown reduced body weight loss and anorexia compared to tumor-bearing controls treated with a non-silencing AAV. Gastrocnemius and total hind limb muscle weight was higher in PrPR knockdown rats. Corticosterone levels were increased in the early phase after tumor induction at day 6 in both groups but returned to baseline levels at day 21 in the PrRP knockdown group. While we did not detect significant changes in gene expression of markers for muscle protein metabolism (MuRF-1, myostatin, mTOR and REDD1), mTOR and REDD1 tended to be lower after disruption PrRP signalling. In conclusion, we identified brainstem PrRP as a possible neuropeptide mediator of CACS in hepatoma tumor-bearing rats. The central and peripheral downstream mechanisms require further investigation and might involve HPA axis activation.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Navarro I Batista K,Schraner M,Riediger Tdoi
10.1016/j.neuropharm.2020.108289subject
Has Abstractpub_date
2020-12-01 00:00:00pages
108289eissn
0028-3908issn
1873-7064pii
S0028-3908(20)30357-9journal_volume
180pub_type
杂志文章abstract：:The present study measured oxygen consumption and core body temperature following central injections of bombesin (1.0 microgram) in food-deprived rats. Oxygen consumption did not differ for bombesin- and control-injected rats while mean core body temperature decreased significantly following bombesin administrations. ...
journal_title：Neuropharmacology
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journal_title：Neuropharmacology
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journal_title：Neuropharmacology
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更新日期：2009-03-01 00:00:00
