Fundamental Study on Assessment of Neurotransplantation Using Nuclear Medicine Imaging

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Alzheimer's disease is one of most troublesome problems encountered in the elderly population. One proposed hypothesis is that a deficit in cholinergic neurotransmission in Alzheimer's disease underlies this serious symptom of the disease. Cholinergic denervation rat model by producing an unilateral lesion of nuleus basalis magnocellularis (NBM) are reported to a model of cognitive deficits, one of instructive models of Alzheimer's disease (AD). The neurotransplantation is now promising as an effective strategy for functional repair in a variety of neural systems in disorders such as Parkinson's disease. In this study autotransplantation of vagal ganglion was performed to NBM lesioned rats. The effects of cholinergic grafts on cholinergic systems evaluated by autoradiographic images in duration of 1,2 and 4 weeks after surgery. Cerebral blood flow (CBF), muscarinic acetylcholine receptor (mAChR), m1 and m2 subtype of AChR-mRNA images were obtained using 99mTc-hexamethyl-propyleneamine … More oxime (99mTc-HMPAO), [3H] quinuculidinal benzilate, 35S-labeled oligonucleotide probes by in situ hybridization respectively. Also acetylcholine transporter images were obtained using [3H] vesamicol and [3H] hemicholinium-3 (3H-HC-3). The autoradiograms were quantified by bio-imaging analyzer using imaging plate ; the regions of interesting (ROIs) were set in cortex of the affected side and unaffected side symmetrically, and the affected-side/unaffected-side ratios (AU ratio) were calculated from these mean photo-stimulated luminescence (PSL) rates. In both NBM lesioned and autoransplanted rats, there were no remarkable changes of the AU ratio at CBF,mAChR,m1mAChR-mRNA and m2mAChR-mRNA images. On the other hand, the [3H] vesamicol images of the NBM lesioned rats showed significant reduction of the mean AU ratio at 1,2 and weeks after lesioning (P<0.01). Furthermore, the mean AU ratio in autotransplanted rats gradually increased and significantly improved 4 weeks after transplantation (p<0.05). There were no remarkable changes of the AU ratio at 3H-HC-3. Clinically emission computed tomography (ECT) with radiolabeled vesamicol may be a potential procedure for the assessment of neurotransplantation therapy on patients with AD. Less