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Age and Time of Day Influences on the Expression of Transforming Growth Factor-Beta and Phosphorylated SMAD3 in the Mouse Suprachiasmatic and Paraventricular Nuclei

Beynon A.L. · Thome J. · Coogan A.N.
Neuroscience and Molecular Psychiatry, Institute of Life Science, School of Medicine, Swansea University, Swansea, UK Neuroimmunomodulation 2009;16:392–399 (DOI:10.1159/000228914)


Background/Aims: 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)-β 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-β and pSMAD3 in the SCN and PVN. Results: We have demonstrated a diurnal pattern of expression of TGF-β in the SCN of young animals, a rhythm that is lost in older mice. The PVN also shows diurnal expression of TGF-β 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. Conclusion: We conclude that TGF-β 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.


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