Amyloid β neurotoxicity in the cholinergic but not in the serotonergic phenotype of RN46A cells

Abstract

Neuropathological examination of brains from AD patients has documented that distinct areas and nuclei are differently affected by the disease. It is unknown as to what extent the neurochemical phenotype plays a role in this process, but particularly acetylcholine (Ach) neurons in the basal forebrain are lost during the progress of the disease. The exact molecular mechanism by which the neuronal death is induced remains unclear, but the amyloid β peptide (A β) is cytotoxic in vitro and may be important for the neuronal cell death in vivo. Previous reports have demonstrated that an immortalized neuronal cell line (RN46A) derived from rat raphe nucleus differentiate in the presence of ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) to a cholinergic and a serotonergic phenotype, respectively [J.S. Rudge et al., Mol. Cell Neurosci. 7 (1996) 204–221]. This study takes advantage of the RN46A cell line to investigate whether the sensitivity to A β is dependent on cell differentiation and neurochemical phenotype. We found that cellular reduction of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) could be inhibited 30–40% by A β in undifferentiated cells. The cholinergic phenotype induced by CNTF remained sensitive to A β whereas the serotonergic phenotype induced by BDNF was unaffected by concentrations of A β up to 10 μM. These findings suggest that differentiation and neurochemical phenotype may play a role for A β induced lesions in Alzheimer's disease.