{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T16:18:21Z","timestamp":1788193101027,"version":"build-2803163510"},"reference-count":42,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2006,6,8]],"date-time":"2006-06-08T00:00:00Z","timestamp":1149724800000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J of Neuroscience"],"published-print":{"date-parts":[[2006,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Balanced dopaminergic cholinergic interactions are crucial for proper basal ganglia function. This is dramatically demonstrated by the worsening of Parkinson's disease symptoms following acetylcholinesterase (AChE) inhibition. Typically, in the brain, the synapse\u2010anchored synaptic AChE (AChE\u2010S) variant is prevalent whereas the soluble readthrough AChE (AChE\u2010R) variant is induced in response to cholinesterase inhibition or stress. Because of the known functional differences between these variants and the fact that AChE\u2010R expression is triggered by various stimuli that themselves are often associated with Parkinson's disease risk, we hypothesized that the splice shift to AChE\u2010R plays a functional role in Parkinsonian progression. After establishing that Paraoxon\u2010induced AChE inhibition indeed aggravates experimental Parkinsonism triggered by the neurotoxin 1\u2010methyl\u20104\u2010phenyl\u20101,2,3,6\u2010tetrahydropyridine (MPTP) in mice, we tested the roles of individual AChE variants by exposing transgenic mice overexpressing either the AChE\u2010S or AChE\u2010R variant to MPTP. Differential reductions of tyrosine hydroxylase levels in the striatum and substantia nigra indicated that transgenic AChE\u2010R expression confers resistance as compared with the parent FVB\/N strain. In contrast, AChE\u2010S overexpression accelerated the MPTP\u2010induced damage. Survival, behavioral measures and plasma corticosterone levels were also compatible with the extent of the dopaminergic damage. Our findings highlight the functional differences between individual AChE variants and indicate that a naturally occurring stress or AChE inhibitor\u2010induced splicing shift can act to minimize dopaminergic cholinergic imbalances. We propose that inherited or acquired alternative splicing deficits could accelerate Parkinsonism and that, correspondingly, adaptive alternative splicing events may attenuate disease progression.<\/jats:p>","DOI":"10.1111\/j.1460-9568.2006.04812.x","type":"journal-article","created":{"date-parts":[[2006,6,8]],"date-time":"2006-06-08T10:51:50Z","timestamp":1149763910000},"page":"2915-2922","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Adaptive acetylcholinesterase splicing patterns attenuate 1\u2010methyl\u20104\u2010phenyl\u20101,2,3,6\u2010tetrahydropyridine\u2010induced Parkinsonism in mice"],"prefix":"10.1111","volume":"23","author":[{"given":"Y.","family":"Ben\u2010Shaul","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"BenMoyal\u2010Segal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Ben\u2010Ari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Bergman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Soreq","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,6,9]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(95)00211-9"},{"key":"e_1_2_7_3_1","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1096\/fj.04-2106fje","article-title":"Acetylcholinesterase\/paraoxonase interactions increase the risk of insecticide\u2010induced Parkinson's disease","volume":"19","author":"BenMoyal\u2010Segal L.","year":"2005","journal-title":"FASEB J."},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.02-0609com"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(01)02626-9"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(99)01501-5"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2003.02230.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00568-3"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-813X(02)00099-2"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1967.00470260014002"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(61)90145-9"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2001.00287.x"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt964"},{"key":"e_1_2_7_14_1","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/0166-2236(95)80019-X","article-title":"The basal ganglia","volume":"18","author":"Graybiel A.M.","year":"1995","journal-title":"Trends Neurosci."},{"key":"e_1_2_7_15_1","first-page":"639","article-title":"Enhanced MPTP neurotoxicity after treatment with isoflurophate or cholinergic agonists","volume":"270","author":"Hadjiconstantinou M.","year":"1994","journal-title":"J. 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