title: Forebrain patterns of c-Fos and FosB induction during cancer-associated anorexia-cachexia in rat.
abstract: Forebrain structures are necessary for the initiation of food intake and its coupling to energy expenditure. The cancer-related anorexia-cachexia syndrome is typified by a prolonged increase in metabolic rate resulting in body weight loss which, paradoxically, is accompanied by reduced food intake. The aim of the present work was to study the forebrain expression of Fos proteins as activation markers and thus to identify potential neurobiological mechanisms favouring catabolic processes or modulating food intake in rats suffering from cancer-related anorexia-cachexia. Neurons in forebrain structures showing most pronounced induction of Fos proteins were further identified neurochemically. To provoke anorexia-cachexia, cultured Morris hepatoma 7777 cells were injected subcutaneously in Buffalo rats. This resulted in a slowly growing tumour inducing approximately 7% body weight loss and a 20% reduction in food intake when the tumour represented 1-2% of body mass. Anorexia-cachexia in these animals was found to be accompanied by Fos induction in several hypothalamic nuclei including the paraventricular and ventromedial hypothalamus, in the parastrial nucleus, the amygdala, the bed nucleus of the stria terminalis, ventral striatal structures and the piriform and somatosensory cortices. Neurochemical identification revealed that the vast majority of FosB-positive neurons in the nucleus accumbens, ventral caudate-putamen and other ventral striatal structures contained prodynorphin or proenkephalin mRNA. These findings indicate that forebrain structures that are part of neuronal networks modulating catabolic pathways and food ingestion are activated during tumour-associated anorexia-cachexia and may contribute to the lack of compensatory eating in response to weight loss characterizing this syndrome.
authors.affiliation: Department of Cell Biology, Faculty of Health Sciences, University of Linköping, S-581 85 Linköping, Sweden. konsman@bordeaux.inserm.fr
authors.forename: Jan Pieter
authors.initials: JP
authors.lastname: Konsman
authors.forename: Anders
authors.initials: A
authors.lastname: Blomqvist
mesh_terms: D000818:Animals; D000855:Anorexia / Q000209:etiology*; D001921:Brain / Q000503:physiopathology*; D002100:Cachexia / Q000209:etiology*; D045744:Cell Line, Tumor; D002149:Energy Intake; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics*; D008114:Liver Neoplasms, Experimental / Q000235:genetics*; D008297:Male; D009928:Organ Specificity; D016548:Prosencephalon / Q000503:physiopathology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D011915:Rats, Inbred BUF; D012016:Reference Values; D014157:Transcription Factors / Q000378:metabolism*; D015431:Weight Loss
chemical_list: C483820:Fosb protein, rat; D016760:Proto-Oncogene Proteins c-fos; D014157:Transcription Factors