Aluminum, NO, and nerve growth factor neurotoxicity in cholinergic neurons
Article first published online: 30 NOV 2001
Copyright © 2001 Wiley-Liss, Inc.
Journal of Neuroscience Research
Volume 66, Issue 5, pages 1009–1018, 1 December 2001
How to Cite
Szutowicz, A. (2001), Aluminum, NO, and nerve growth factor neurotoxicity in cholinergic neurons. J. Neurosci. Res., 66: 1009–1018. doi: 10.1002/jnr.10040
- Issue published online: 30 NOV 2001
- Article first published online: 30 NOV 2001
- Manuscript Accepted: 21 AUG 2001
- Manuscript Revised: 20 AUG 2001
- Manuscript Received: 19 MAY 2001
- KBN. Grant Numbers: 6P04A 0817, 4P05A 10019
Several neurotoxic compounds, including Al, NO, and β-amyloid may contribute to the impairment or loss of brain cholinergic neurons in the course of various neurodegenerative diseases. Genotype and phenotypic modifications of cholinergic neurons may determine their variable functional competency and susceptibility to reported neurotoxic insults. Hybrid, immortalized SN56 cholinergic cells from mouse septum may serve as a model for in vitro cholinotoxicity studies. Differentiation by various combinations of cAMP, retinoic acid, and nerve growth factor may provide cells of different morphologic maturity as well as activities of acetylcholine and acetyl-CoA metabolism. In general, differentiated cells appear to be more susceptible to neurotoxic signals than the non-differentiated ones, as evidenced by loss of sprouting and connectivity, decreases in choline acetyltransferase and pyruvate dehydrogenase activities, disturbances in acetyl-CoA compartmentation and metabolism, insufficient or excessive acetylcholine release, as well as increased expression of apoptosis markers. Each neurotoxin impaired both acetylcholine and acetyl-CoA metabolism of these cells. Activation of p75 or trkA receptors made either acetyl-CoA or cholinergic metabolism more susceptible to neurotoxic influences, respectively. Neurotoxins aggravated detrimental effects of each other, particularly in differentiated cells. Thus brain cholinergic neurons might display a differential susceptibility to Al and other neurotoxins depending on their genotype or phenotype-dependent variability of the cholinergic and acetyl-CoA metabolism. © 2001 Wiley-Liss, Inc.