Open AccessExcess “read-through” acetylcholinesterase attenuates but the “synaptic” variant intensifies neurodeterioration correlates
Author(s) -
M. Sternfeld,
Shai Shoham,
Omer Klein,
César FloresFlores,
Tamah Evron,
Gregory H. Idelson,
Dani Kitsberg,
James W. Patrick,
Hermona Soreq
Publication year - 2000
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.140004597
Subject(s) - acetylcholinesterase , aché , hippocampus , neurodegeneration , medicine , neuroscience , endocrinology , genetically modified mouse , chemistry , biology , transgene , enzyme , biochemistry , disease , gene
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.