Adenoviral vector-mediated expression of neurotrophin-3 increases neuronalsurvival in suprachiasmatic nucleus grafts

To improve transplantation results of fetal suprachiasmatic nucleus (SCN) i n SCN-lesioned (SCNX) rats, grafts were ex vivo transduced with an adenovir al vector encoding for neurotrophin-3 (AdNT-3) before implantation. Mock- a nd AdLacZ-transduced grafts were used as controls. First, transplants were evaluated microscopically and by image analysis for the presence of vasopre ssinergic (VPergic) and vasoactive intestinal polypeptidergic (VIPergic) SC N neurons at 10 weeks or later postgrafting. Ex vivo AdNT-8-transduced tran splants displayed increased volume areas of VPergic and VIPergic SCN cells in comparison with those in mock- and AdLacZ-transduced transplants, but si gnificantly improved graft-to-host VPergic and VIPergic SCN fiber growth wa s not reached (though AdNT-3-transduced transplants tended to grow more VPe rgic fibers into the brain of VP-deficient SCNX Brattleboro rat recipients, which were chosen as recipients to circumvent the presence of non-SCN VP f iber staining). Second, a small group of arrhythmic Wister rats received Ad NT-3- or control-treated SCN grafts while continuously on-line for the moni toring of overt circadian activities in the pre- and postgrafting periods. The results indicated that ex vivo transduced SCN grafts can still restore arrhythmia, but that the NT-3-mediated anatomical improvements of the graft ing results were not sufficient to enhance efficacy of reinstatement of cir cadian rhythm in SCN-lesioned rats. However, in this group VIP staining vol ume area, not VP staining volume area, correlated significantly with reinst atement of circadian rhythm. (C) 2001 Academic Press.