title: Adaptive alternative splicing correlates with less environmental risk of parkinsonism.
abstract: OBJECTIVE
  Environmental exposure to anti-acetylcholinesterases (AChEs) aggravates the risk of Parkinsonism due to currently unclear mechanism(s). We explored the possibility that the brain's capacity to induce a widespread adaptive alternative splicing response to such exposure may be involved.
  
  
  METHODS
  Following exposure to the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), brain region transcriptome profiles were tested.
  
  
  RESULTS
  Changes in transcript profiles, alternative splicing patterns and splicing-related gene categories were identified. Engineered mice over-expressing the protective AChE-R splice variant showed less total changes but more splicing-related ones than hypersensitive AChE-S over-expressors with similarly increased hydrolytic activities. Following MPTP exposure, the substantia nigra and prefrontal cortex (PFC) of both strains showed a nuclear increase in the splicing factor ASF/SF2 protein. Furthermore, intravenous injection with highly purified recombinant human AChE-R changed transcript profiles in the striatum.
  
  
  CONCLUSIONS
  Our findings are compatible with the working hypothesis that inherited or acquired alternative splicing deficits may promote parkinsonism, and we propose adaptive alternative splicing as a strategy for attenuating its progression.
authors: Department of Biological Chemistry, Life Sciences Institute, Hebrew University of Jerusalem, Jerusalem, Israel.
authors: Liat
authors: L
authors: Benmoyal-Segal
authors: Lilach
authors: L
authors: Soreq
authors: Yoram
authors: Y
authors: Ben-Shaul
authors: Shani
authors: S
authors: Ben-Ari
authors: Tehila
authors: T
authors: Ben-Moshe
authors: Sigal
authors: S
authors: Aviel
authors: Hagai
authors: H
authors: Bergman
authors: Hermona
authors: H
authors: Soreq
mesh_terms: D000110:Acetylcholinesterase / Q000235:genetics*; D000220:Adaptation, Biological; D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D016000:Cluster Analysis; D004781:Environmental Exposure / Q000009:adverse effects; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D020734:Parkinsonian Disorders / Q000201:enzymology / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000235:genetics; D012307:Risk Factors
chemical_list: D007527:Isoenzymes; D011994:Recombinant Proteins; D000110:Acetylcholinesterase