Autism Studies and Related Medical Conditions, January 2009 - TACA

Publication Types:
Review
PMID: 12123643 [PubMed - indexed for MEDLINE]
14: J Neurosci Res. 2001 Dec 1;66(5):1009-18.
Aluminum, NO, and nerve growth factor neurotoxicity in cholinergic neurons.
Szutowicz A.
Chair of Clinical Biochemistry, Department of Laboratory Medicine, Medical
University of Gdańsk, Debinki 7, 80-211 Gdańsk, Poland. aszut@amg.gda.pl
Several neurotoxic compounds, including Al, NO, and beta-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. Copyright 2001
Wiley-Liss, Inc.
Publication Types:
Research Support, Non-U.S. Gov't
Review
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