Neural Transplantation in Animal Models of Dementia

Abstract

Neural transplantation provides a powerful novel technique for investigating the neurobiological basis and potential strategies for repair of a variety of neurodegenerative conditions. The present review considers applications of this technique to dementia. After a general introduction (section 1), attempts to replace damaged neural systems by transplantation are considered in the context of distinct animal models of dementia. These include grafting into aged animals (section 2), into animals with neurotransmitter-selective lesions of subcortical nuclei, in particular involving basal forebrain cholinergic systems (section 3), and into animals with non-specific lesions of neocortical and hippocampal systems (section 4). The next section considers the alternative use of grafts as a source of growth/trophic factors to inhibit degeneration and promote regeneration in the aged brain (section 5). Finally, a number of recent studies have employed transplanted tissues to model and study the neurodegenerative processes associated with ageing and Alzheimer's disease taking place within the transplant itself (section 6). It is concluded (section 7) that although neural transplantation does not offer any immediate prospect of therapeutic repair in clinical dementia, the technique does offer a powerful neurobiological tool for studying the neuropathological processes involved in both spontaneous degeneration and specific diseases of ageing. New understandings derived from neural transplantation may be expected to lead to rational development of novel strategies to inhibit the neurodegenerative process and to promote regeneration in the aged brain.