The aging suprachiasmatic nucleus and cytokines: Functional, molecular, and cellular changes in rodents

The aging process brings about a switch to a low- grade chronic inflammatory condition in the periphery and brain, a condition which may prime brain cells, including those of the hypothalamic suprachiasmatic nucleus (SCN). Little information is available, however, on the responses of the SCN to neuroinflammation and immune-related challenges, and such responses have not been hitherto investigated during aging. We here provide an overview of these issues and summarize data we obtained in the study of the SCN of young and aged mice. In particular, we analyzed: i) the electrophysiological properties of the SCN core (the retino-recipient region) in tissue slices; ii) expression and day/night variation of transcripts encoding the receptors for the cytokines interferon-gamma and tumor necrosis factor-alpha, as well as the expression of transcripts encoding the proteins "suppressors of cytokine signaling" SOCS1 and SOCS3, by means of quantitative real-time polymerase chain reaction; levels of mRNAs were correlated with neuronal activation, revealed by Fos induction, elicited in the SCN by intracerebroventricular injections of a mixture of interferon-gamma and tumor necrosis factor-alpha during the daytime and nighttime; and iii) response of astrocytes and microglia in the SCN to the same paradigm of cytokine administration. Marked changes of all the above-mentioned parameters were found in the aged SCN, indicating that the circadian pacemaker is a target of the aging process. In addition, the findings indicate that neurons and glial cells of the biological clock are sensitive to inflammatory signals, and that the response to such signals is altered during senescence.