Amyloid ß-peptides injection into the cholinergic nuclei: Morphological, neurochemical and behavioral effects

This chapter focuses on the actions of β-peptides in the nucleus basalis (NB) at longer times post-injection. The effects of β-peptides on acetyltransferase (ChAT) immunoreactivity (IR), cortical acetylcholine (ACh) release and behavior are examined. The chapter investigates the toxicity of β-peptides to the cholinergic neurons by direct injection in the forebrain of the rat. As it is reported that the neurotoxic activity of β-amyloid resides within the 25–35 portion of the peptide, the full-length peptide β and the β-peptide are studied. The chapter demonstrates that the administration of β-peptides into the medial septum is followed by a decrease in ACh release from the hippocampus. The chapter also studies the histological and functional changes due to the presence in the NB of β-peptide deposits. It concludes that local injections of amyloid peptides in the rat NB result in local damage and cholinergic hypofunction. However, only the β-(1-40) and β-(25-35) peptides, but not the scrambled form congophilic fibrillary deposits, and induce some behavioral impairment, with the most persistent decrease in the number of cholinergic neurons and ACh release brought about by β-(1- 40). Because the deposit formed by the β-(l-40) peptide lasts largely unaltered for a long time, the injection of this peptide may be a useful model for investigating the temporal progression and neurotoxic effects of an amyloid plaque.