Selective Death of Cholinergic Septohippocampal Neurons Induced by Colchicine: the Role of Axoplasmic Transport

Abstract

Alzheimer’s disease (AD) is characterized in part by the degeneration of specific sets and types of neurons. Of particular interest is the dramatic loss of cholinergic neurons in the basal forebrain (Coyle et al., 1983). Another characteristic feature of the AD brain is the presence of neurofibrillary tangles and amyloid-containing plaques (Terry and Katzman, 1983). The cause of these degenerative events is not known, and in fact the relationship between plaques and tangles and neuronal degeneration is unclear. It has been hypothesized that impairment of the microtubule system and disruption of axoplasmic transport play an important role in the pathogenesis of the disease (Gajdusek, 1985; Matsuyama and Jarvik, 1989) possibly resulting in plaques, tangles and neuronal degeneration. In the present chapter we shall describe our own work using the microtubule inhibitor colchicine for inducing the selective death of cholinergic neurons in the medial septum. In preparation for this, we shall first give a brief review of the structure and function of microtubules and of the action of colchicine.KeywordsNerve Growth FactorCholinergic NeuronBasal ForebrainMedial SeptumPaired Helical FilamentThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.