Effects of grafts containing cholinergic and/or serotonergic neurons on cholinergic, serotonergic and noradrenergic markers in the denervated rat hippocampus

Abstract

Long-Evans female rats sustained aspirative lesions of the septohippocampal pathways and, 2 weeks later, received intrahippocampal suspension grafts prepared from the regions including either the medial septum and the diagonal band of Broca (group S), or the mesencephalic raphe (group R), or from both these regions together (group S+R). Sham-operated (group SHAM) and lesion-only (group LES) rats were used as controls. Six months after grafting, high affinity synaptosomal uptake of choline (HACU) and serotonin (HASU), choline acetyltransferase (ChAT) activity and, using HPLC, the content of serotonin ([5-HT]), 5-hydroxyindolacetic acid ([5-HIAA]) and noradrenaline ([NA]) were determined in three rostro-caudal segments of the hippocampus (designated hereafter as the dorsal, the ‘middle’ and the ventral segments). In all three segments of the dorsal hippocampus, septohippocampal lesions decreased HACU, ChAT activity, HASU and [5-HT]; [5-HIAA] was decreased only in the middle and ventral hippocampal segments. The lesions also resulted in an above normal increase of [NA]. Septal grafts increased HACU and ChAT in the three hippocampal regions, had no effect on serotonergic markers and attenuated the lesion-induced increase of [NA] in only the dorsal and middle hippocampal segments. Raphe grafts increased HASU, [5-HT] and [5-HIAA] in the dorsal and middle hippocampal segments, had no effects on cholinergic markers and did not affect the lesion-induced increase of [NA]. Co-grafts increased HACU, ChAT activity, HASU, [5-HT] and [5-HIAA], and attenuated the lesion-induced increase of [NA]. These data demonstrate that grafts of fetal neurons placed into the denervated hippocampus may induce a neurochemical recovery which depends upon the anatomical origin of the grafted cells. They also show that co-grafting allows to combine the neurochemical properties of two fetal brain regions grafted separately. Furthermore, our findings suggest that graft-derived cholinergic reinnervation of the hippocampus prevents the lesion-induced increase of noradrenaline concentration which is likely to result from sympathetic sprouting. Thus, our data confirm the results of a previous experiment carried out at a post-grafting delay of 10–11 months, and show that the graft-induced effects reported previously are already massively present by 6 months after surgery.