Excess "read-through" acetylcholinesterase attenuates but the "synaptic'" variant intensifies neurodeterioration correlates

Acute stress increases the risk for neurodegeneration, but the molecular si gnals regulating the shift from transient stress responses to progressive d isease are not yet known. The "read-through" variant of acetylcholinesteras e (AChE-R) accumulates in the mammalian brain under acute stress. Therefore , markers of neurodeterioration were examined in transgenic mice overexpres sing either AChE-R or the "synaptic" AChE variant, AChE-s. Several observat ions demonstrate that excess AChE-R attenuates, whereas AChE-s intensifies, neurodeterioration. In the somatosensory cortex, AChE-S transgenics, but n ot AChE-R or control FVB/N mice, displayed a high density of curled neurona l processes indicative of hyperexcitation. In the hippocampus, AChE-s and c ontrol 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 tha t AChE-R serves as a modulator that may play a role in preventing the shift from transient, acute stress to progressive neurological disease.