Behavioral effects of systemic transforming growth factor-alpha in Syrian hamsters

• Published in: Behavioural brain research 2009-03, Vol.198 (2), p.440-448
• Main Authors: Gilbert, Jenifer, Davis, Fred C.
• Format: Article
• Language: English
• Subjects: Animals; Behavioral psychophysiology; Biological and medical sciences; Cachexia; Circadian; Cricetinae; Eating - drug effects; EGF; Extracellular Signal-Regulated MAP Kinases - metabolism; Extracellular Signal-Regulated MAP Kinases - physiology; Fundamental and applied biological sciences. Psychology; Hypothalamus - cytology; Hypothalamus - metabolism; Immunohistochemistry; Infusions, Subcutaneous; Injections, Intraperitoneal; Male; Mesocricetus; Mitogen-Activated Protein Kinase 3 - metabolism; Neurons - metabolism; Paraventricular nucleus; Phosphorylation - drug effects; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Signal Transduction - drug effects; Suprachiasmatic; TGF-α; Third Ventricle - cytology; Third Ventricle - metabolism; Time Factors; Transforming Growth Factor alpha - administration & dosage; Transforming Growth Factor alpha - pharmacology; Transforming Growth Factor alpha - physiology; Weight Loss - drug effects
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2008.11.046

The growth factor, transforming growth factor-alpha (TGF-α) is strongly expressed in the hypothalamic circadian pacemaker, the suprachiasmatic nucleus (SCN). TGF-α is one of several SCN peptides recently suggested to function as a circadian output signal for the regulation of locomotor activity rhythms in nocturnal rodents. When infused in the brain, TGF-α suppresses activity. TGF-α suppresses other behaviors as well including feeding, resulting in weight loss. Elevated TGF-α is correlated with some cancers, and it is possible the TGF-α and its receptor, the epidermal growth factor receptor (EGFR), mediate fatigue and weight loss associated with cancer. If true for cancers outside of the brain, then systemic TGF-α should also affect behavior. We tested this hypothesis in hamsters with intraperitoneal injections or week-long subcutaneous infusions of TGF-α. Both treatments suppressed activity and infusions caused reduced food consumption and weight loss. To identify areas of the brain that might mediate these effects of systemic TGF-α, we used immunohistochemistry to localize cells with an activated MAP kinase signaling pathway (phosphorylated ERK1). Cells were activated in two hypothalamic areas, the paraventricular nucleus and a narrow region surrounding the third ventricle. These sites could not only be targets of TGF-α produced in the SCN but could also mediate effects of elevated TGF-α from tumors both within and outside the central nervous system.