Cell Biology of the Forebrain Cholinergic Neurons: Effects of NGF, Triiodothyronine and Gangliosides

Alzheimer’s disease is associated with a selective loss of cholinergic neurons located in the basal forebrain. Even though other neuronal systems are also partly affected, the loss of cholinergic neurons is regarded by most investigators as being the principal factor responsible for the memory loss that is characteristic of Alzheimer’s disease (Bartus et al., 1982; Coyle et al., 1983; Davies, 1985). In attempting to find the cause of and treatment for the disease, I decided to study the cell biology of cholinergic neurons of the forebrain and to characterise their requirements for survival and maintenance of function. A culture system was developed in which cholinergic neurons from rat brains are grown and studied under controlled conditions and are easily accessible for observation. Using these cultures, the effects of other cell types, growth factors, hormones and drugs on survival, growth and differentiation of cholinergic cells are investigated. These studies will lead to a characterisation of the conditions required by cholinergic neurons to survive and maintain their function in vitro. Conditions and compounds found to affect cholinergic neurons in vitro will later be assessed in living animals with specific lesions of the cholinergic systems. The in vitro studies first focussed on the effects of NGF and thyroxine, which were both reported to influence cholinergic neurons, and on gangliosides, which were claimed to promote neuronal survival and regeneration.