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

Behav Brain Res. 2009 Mar 17;198(2):440-8. doi: 10.1016/j.bbr.2008.11.046. Epub 2008 Dec 6.

Abstract

The growth factor, transforming growth factor-alpha (TGF-alpha) is strongly expressed in the hypothalamic circadian pacemaker, the suprachiasmatic nucleus (SCN). TGF-alpha 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-alpha suppresses activity. TGF-alpha suppresses other behaviors as well including feeding, resulting in weight loss. Elevated TGF-alpha is correlated with some cancers, and it is possible the TGF-alpha 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-alpha should also affect behavior. We tested this hypothesis in hamsters with intraperitoneal injections or week-long subcutaneous infusions of TGF-alpha. 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-alpha, 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-alpha produced in the SCN but could also mediate effects of elevated TGF-alpha from tumors both within and outside the central nervous system.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cricetinae
  • Eating / drug effects*
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Extracellular Signal-Regulated MAP Kinases / physiology
  • Hypothalamus / cytology
  • Hypothalamus / metabolism
  • Immunohistochemistry
  • Infusions, Subcutaneous
  • Injections, Intraperitoneal
  • Male
  • Mesocricetus
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Neurons / metabolism*
  • Phosphorylation / drug effects*
  • Signal Transduction / drug effects
  • 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*

Substances

  • Transforming Growth Factor alpha
  • Extracellular Signal-Regulated MAP Kinases
  • Mitogen-Activated Protein Kinase 3