A New Animal Model of Alzheimer’s Disease by Selective Destruction of the Cholinergic Neurons in the Basal Forebrain
In Alzheimer’s disease (AD), several neurochemical and pathological changes have been reported. Among them, the decrease of acetylcholine in the cerebral cortex and selective degeneration of the basal magnocellular nucleus of Meynert(BMN), sending cholinergic projections to the cortex, were the most conspicuous findings (Davies and Maloney, 1976; Whitehouse et al., 1982; Friedman et al., 1983; Beatty et al., 1986; Mesulam, 1986). In order to analyze the pathogenic mechanism(s) of AD, various attempts to produce an animal model of AD have been made (Coyle and Schwarcz, 1983; Smith, 1988). The neurons in the BMN have been destroyed by electrical means and by injection of axon-sparing neurotoxins such as kainic acid and ibotenic acid. However, not only cholinergic neurons but also noncholinergic neurons in the BMN are destroyed by these methods. In addition, by the electric destruction a number of cholinergic or non-cholinergic passing fibers are also destroyed. Quinolic acid, an endogenous neurotoxin, has the same drawback as the other neurotoxins. Sofroniew and Pearson(1985) reported the transneural retrograde degeneration of BMN neurons by topical application of kainic acid or N-methyl-D-aspartic acid on the cortex. The events were specific neither to the cholinergic system nor to kainic acid. On the other hand, injection of ethylcholine mustard aziridinium ion (AF 64A), a specific cholinotoxin, was made in order to produce an animal model of AD (Walh et al., 1984). However, because AF64A affects all the cholinergic neurons, it could also affect passing cholinergic fibers in the BMN when applied. Furthermore, the possibility that AF64A has an affect on noncholinergic systems should be considered. Accordingly, an attempt to develop a method that selectively destroys the cholinergic neuron in the BMN is needed.
KeywordsNerve Growth Factor Passive Avoidance Cholinergic Neuron Basal Forebrain Kainic Acid
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