Autotransplantation of peripheral cholinergic neurons into the brains of Alzheimer model rats.

Abstract

Current hypotheses regarding Alzheimer's disease implicate cholinergic function. In this study, peripheral cholinergic neurons in the vagal nodosal ganglion were transplanted into the brains of Alzheimer model rats. Eighteen Sprague-Dawley strain rats were divided into three groups: 1) unoperated control rats, 2) rats that had undergone bilateral destruction of the nucleus basalis of Meynert (NBM) (Alzheimer model), and 3) the transplantation group in which the vagal nodosal ganglion was transplanted into the cerebral neocortex one week after the bilateral destruction of the Meynert nucleus. Seven weeks after the transplantation rat behaviour was assessed using psychological tests (spontaneous activity, passive avoidance response and the Hebb-Williams maze test). The Alzheimer model rats had a statistically significant increase in spontaneous activity in comparison with controls (P less than 0.01). The transplant rats showed some amelioration of this abnormal increase in spontaneous activity observed in the Alzheimer model rats. All of the control rats showed conditioned passive avoidance responses, while only one Alzheimer model rat retained is shocked-conditions behaviour before 24 hours (P less than 0.01). Three of the six transplanted rats showed complete improvement in the passive avoidance response test. In the Hebb-Williams maze test, the rats with NMB lesions made more errors than the control rats. The transplanted rats had a lower number of errors than NBM-lesioned rats but still more than the controls. Histological examination revealed many cholinergic cells in the transplanted tissue, especially in the area adjacent to the cerebral cortical surface. The present results indicate that autotransplantation of peripheral cholinergic cells ameliorates abnormal behaviour in Alzheimer model rats.