Excess "read-through" acetylcholinesterase attenuates but the "synaptic" variant intensifies neurodeterioration correlates.
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.
Sternfeld
M
M
The Eric Roland Center for Neurodegenerative Diseases, Department of Biological Chemistry, Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Shoham
S
S
Klein
O
O
Flores-Flores
C
C
Evron
T
T
Idelson
G H
GH
Kitsberg
D
D
Patrick
J W
JW
Soreq
H
H
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
D007527:Isoenzymes; D000110:Acetylcholinesterase