title: Excess "read-through" acetylcholinesterase attenuates but the "synaptic" variant intensifies neurodeterioration correlates.
abstract: Acute stress increases the risk for neurodegeneration, but the molecular signals regulating the shift from transient stress responses to progressive disease are not yet known. The "read-through" variant of acetylcholinesterase (AChE-R) accumulates in the mammalian brain under acute stress. Therefore, markers of neurodeterioration were examined in transgenic mice overexpressing either AChE-R or the "synaptic" AChE variant, AChE-S. Several observations demonstrate that excess AChE-R attenuates, whereas AChE-S intensifies, neurodeterioration. In the somatosensory cortex, AChE-S transgenics, but not AChE-R or control FVB/N mice, displayed a high density of curled neuronal processes indicative of hyperexcitation. In the hippocampus, AChE-S and control mice, but not AChE-R transgenics, presented progressive accumulation of clustered, heat shock protein 70-immunopositive neuronal fragments and displayed a high incidence of reactive astrocytes. Our findings suggest that AChE-R serves as a modulator that may play a role in preventing the shift from transient, acute stress to progressive neurological disease.
authors.affiliation: The Eric Roland Center for Neurodegenerative Diseases, Department of Biological Chemistry, Hebrew University of Jerusalem, Jerusalem 91904, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Sternfeld
authors.forename: S
authors.initials: S
authors.lastname: Shoham
authors.forename: O
authors.initials: O
authors.lastname: Klein
authors.forename: C
authors.initials: C
authors.lastname: Flores-Flores
authors.forename: T
authors.initials: T
authors.lastname: Evron
authors.forename: G H
authors.initials: GH
authors.lastname: Idelson
authors.forename: D
authors.initials: D
authors.lastname: Kitsberg
authors.forename: J W
authors.initials: JW
authors.lastname: Patrick
authors.forename: H
authors.initials: H
authors.lastname: Soreq
mesh_terms: D000110:Acetylcholinesterase / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001253:Astrocytes / Q000166:cytology; D001921:Brain / Q000002:abnormalities / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009474:Neurons; D011817:Rabbits; D013315:Stress, Psychological; D013569:Synapses / Q000201:enzymology
chemical_list: D007527:Isoenzymes; D000110:Acetylcholinesterase