Loss of responsiveness to melatonin in the aging mouse suprachiasmatic nucleus
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Document Type
Journal ArticlePublication Date
2008-03-01Keywords
Age Factors*Aging
Animals
CREB-Binding Protein
Drug Interactions
Melatonin
Metallothionein
Mice
Mice, Knockout
Neurotransmitter Agents
Phosphorylation
Pituitary Adenylate Cyclase-Activating Polypeptide
Suprachiasmatic Nucleus
Neuroscience and Neurobiology
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Show full item recordAbstract
Melatonin modulates circadian rhythms via the hypothalamic suprachiasmatic nucleus (SCN). One of the most robust assays for SCN melatonin receptor activation in mice is the inhibition of PACAP-induced phosphorylation of the transcription factor Ca(2+)/cAMP responsive element binding protein (CREB). To assess the effect of aging on responsiveness to melatonin, SCN slices from mice of different ages were prepared and treated with PACAP alone or PACAP plus melatonin. CREB phosphorylation state was assessed by immunohistochemistry. In SCN slices from young (2-4-month-old) mice, melatonin reduced the level of phospho-CREB immunoreactivity following PACAP treatment in a dose-dependent manner. In SCN slices from aged mice (19-22 months of age), PACAP alone induced comparable levels of phospho-CREB, but melatonin treatment failed to inhibit the PACAP-induced CREB phosphorylation. The results indicate an age-related loss of sensitivity to melatonin in the SCN. The findings are discussed in the context of the impact of endogenous and exogenous melatonin on sleep in elderly humans.Source
Neurobiol Aging. 2008 Mar;29(3):464-70. Epub 2006 Nov 22. Link to article on publisher's siteDOI
10.1016/j.neurobiolaging.2006.10.015Permanent Link to this Item
http://hdl.handle.net/20.500.14038/38004PubMed ID
17123666Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1016/j.neurobiolaging.2006.10.015