Cancer-induced anorexia and malaise are mediated by CGRP neurons in the parabrachial nucleus.
Nat Neurosci
; 20(7): 934-942, 2017 Jul.
Article
em En
| MEDLINE
| ID: mdl-28581479
ABSTRACT
Anorexia is a common manifestation of chronic diseases, including cancer. Here we investigate the contribution to cancer anorexia made by calcitonin gene-related peptide (CGRP) neurons in the parabrachial nucleus (PBN) that transmit anorexic signals. We show that CGRPPBN neurons are activated in mice implanted with Lewis lung carcinoma cells. Inactivation of CGRPPBN neurons before tumor implantation prevents anorexia and loss of lean mass, and their inhibition after symptom onset reverses anorexia. CGRPPBN neurons are also activated in Apcmin/+ mice, which develop intestinal cancer and lose weight despite the absence of reduced food intake. Inactivation of CGRPPBN neurons in Apcmin/+ mice permits hyperphagia that counteracts weight loss, revealing a role for these neurons in a 'nonanorexic' cancer model. We also demonstrate that inactivation of CGRPPBN neurons prevents lethargy, anxiety and malaise associated with cancer. These findings establish CGRPPBN neurons as key mediators of cancer-induced appetite suppression and associated behavioral changes.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Anorexia
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Peptídeo Relacionado com Gene de Calcitonina
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Carcinoma Pulmonar de Lewis
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Comportamento de Doença
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Núcleos Parabraquiais
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Neoplasias
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos