It's well known that food-associated cues, such as advertising, can influence food intake. But the underlying neurobiology is far from clear. Craig A. Schiltz and colleagues from the University of Wisconsin Madison School of Medicine and Public Health, USA, created an experimental set up that allowed them to study patterns of gene expression linked to this motivational state - rats conditioned to expect a chocolate-flavoured treat in a particular environment, were subsequently denied their reward.
The research, conducted in the laboratory of Ann E. Kelly showed that expression of a handful of immediate early genes was increased in cortical, striatal, thalamic and hypothalamic brain regions. Food-related cues triggered dramatic changes in the functional connectivity of circuits involved in adaptive behaviour. For example, increased connectivity was seen between the cortex and two other regions - the amygdala and the striatum. Within the latter, there was a shift in activity from the outer shell to the inner core of the nucleus accumbens and an increased expression of the opioid-encoding proenkephalin gene.
Taken together, these results suggest that food-associated cues have a powerful influence on neuronal activity and gene expression in brain areas mediating complicated functions such as cognition and emotion, and more basic abilities such as arousal and energy balance. The pattern of activation differs from that elicited by neutral cues, and may well contribute to a conditioned motivational state that can lead to excessive food intake
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"They're all occurring together on a single chromosome, which results in a greatly increased amount of EGFR, he said. The predicted end result would be a great increase in EGFR protein production in the affected cells, driving them toward cancer.
These findings might explain why East Asians are known to respond better than other ethnic groups to a type of chemotherapy that inhibits EGFR activity, Dr. Gazdar said.
Cancer cells become addicted to EGFR, he said, so these cells are much more susceptible to the cancer-killing effect of EGFR inhibitors.
This type of analysis of cancer genes might be helpful for other types of cancer and other ethnic groups, Dr. Gazdar said, possibly explaining both the different manifestations of the disease seen among ethnic groups and leading the way to matching a specific treatment to the patient.
Other UT Southwestern researchers involved in the study were Dr. Pila Estess, assistant professor of pathology; Dr. Mark Siegelman, associate professor of pathology; Dr. Jerry Shay, professor of cell biology; and Dr. John Minna, professor of internal medicine and director of the Nancy B. and Jake L. Hamon Center for Therapeutic Oncology Research and the W.A. Tex and Deborah Moncrief Jr. Center for Cancer Genetics.
Researchers from Fred Hutchinson Cancer Research Center in Seattle, Tokyo Medical University, the Center of Excellence in Aging in Chieti, Italy, and UT M.D. Anderson Cancer Center also participated, as did visiting researchers from Chiba University Medical School, Okayama University Medical School and Gifu University Medical School, all in Japan.
The work was supported by the National Cancer Institute.
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