Fetal tissue containing the suprachiasmatic nucleus restores multiple circadian rhythms in old rats

The suprachiasmatic nucleus (SCN) is the major circadian pacemaker in mammals. When fetal tissue containing the SCN is transplanted into young rats whose circadian rhythms have been abolished by SCN lesions, the rhythms gradually reappear. Circadian rhythms in many rats deteriorate or disappear with age. The rationale of the present study was that old rats with poor circadian rhythms resemble young rats with SCN lesions. If there is a similar mechanism underlying this resemblance, then fetal tissue containing the SCN should restore rhythms in old rats. Therefore, we implanted such tissue into the third ventricle of intact aged rats with poor circadian rhythms. Body temperature, locomotor activity, and/or drinking were measured simultaneously within subjects. Grafts and hosts were stained immunocytochemically for vasoactive intestinal polypeptide (VIP), arginine vasopressin (AVP), and neuropeptide Y (NPY). Of 23 SCN grafts, 14 were viable (cells observable with Nissl or peptide staining). In 7 of the 14 aged hosts, up to three circadian rhythms were improved or restored. VIP cells were always observable, which was not the case for AVP cells or NPY fibers. In the other seven hosts, no circadian rhythm was improved. Compared with the successful grafts, these unsuccessful grafts had similar amounts of AVP and NPY staining but significantly less VIP cell and/or fiber staining. Fetal cerebellar grafts, which do not contain any of the three peptides, did not improve or restore any rhythms. Thus the degeneration of circadian rhythms in aged rats may be due, at least in part, to deterioration of the aged SCN and in particular, to a loss of function of VIP-containing neurons.