title: Age and time of day influences on the expression of transforming growth factor-beta and phosphorylated SMAD3 in the mouse suprachiasmatic and paraventricular nuclei.
abstract: OBJECTIVE
  The master mammalian circadian pacemaker is the suprachiasmatic nuclei (SCN) of the hypothalamus. In this study we examined the expression of transforming growth factor (TGF)-beta and the associated signaller phosphorylated SMAD3 (pSMAD3) in the SCN and the paraventricular nucleus (PVN) of the hypothalamus of the young and older mouse across the diurnal cycle, in order to ascertain whether there are time-of-day and age influences on their expression in the hypothalamus.
  
  
  METHODS
  Immunohistochemistry coupled to densitometric analysis has been used to quantitate the expression of TGF-beta and pSMAD3 in the SCN and PVN.
  
  
  RESULTS
  We have demonstrated a diurnal pattern of expression of TGF-beta in the SCN of young animals, a rhythm that is lost in older mice. The PVN also shows diurnal expression of TGF-beta and older mice exhibit elevated levels. Finally, we have demonstrated a novel day/night difference in the expression of pSMAD3, a part of the TGF signalling pathway, in the SCN, a rhythm that appears to be lost with age.
  
  
  CONCLUSIONS
  We conclude that TGF-beta and pSMAD3 are expressed under basal conditions in the SCN and PVN, and this expression is modulated in both a diurnal and age-dependent manner.
authors.affiliation: Neuroscience and Molecular Psychiatry, Institute of Life Science, School of Medicine, Swansea University, Swansea, UK.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Beynon
authors.forename: Johannes
authors.initials: J
authors.lastname: Thome
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Coogan
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001931:Brain Mapping; D002940:Circadian Rhythm / Q000502:physiology*; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism*; D010766:Phosphorylation; D015398:Signal Transduction / Q000502:physiology; D051900:Smad3 Protein / Q000378:metabolism*; D013493:Suprachiasmatic Nucleus / Q000378:metabolism*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D016212:Transforming Growth Factor beta