title: REST/NRSF-induced changes of ChAT protein expression in the neocortex and hippocampus of the 3xTg-AD mouse model for Alzheimer's disease.
abstract: OBJECTIVE
  The cholinergic system is one of the neurotransmitter systems altered in Alzheimer's disease (AD), the most common form of human dementia. The objective of this work was to determine the REST/NRSF involvement in altered ChAT expression in the neocortex and hippocampus of an AD transgenic mouse (homozygous 3xTg-AD) that over-expresses 3 proteins, amyloid-β precursor protein, presenilin-1, and tau, all of which are associated with AD and cause cellular degeneration.
  
  
  METHODS
  Two groups (WT and 3xTg-AD) of 11-month-old female mice were analyzed and compared. Half of the brains of each group were used for ChAT immunohistochemistry, and Western Blot analyses of ChAT and REST/NRSF were performed on the other half.
  
  
  RESULTS
  We observed significant decreases in the number of ChAT-immunoreactive cells in the Meynert nucleus and of fibers in the frontal motor cortex and hippocampal CA1 area in transgenic mice compared with control mice. An increased level of REST/NRSF protein and a reduction of ChAT protein expression in the 3xTg-AD mice compared with their controls were also found in both in the latter two cerebral regions.
  
  
  CONCLUSIONS
  The increased REST/NRSF expression reported here and its effect on the regulatory region for ChAT transcription could explain the decreased expression of ChAT in the 3xTg-AD mouse; these findings may be associated with the degeneration observed in AD.
authors.affiliation: Centro Universitario de Ciencias Biológicas y Agropecuarias, Universidad de Guadalajara, Zapopan, Jal. CP 45110, México; University of CA, Irvine Campus, USA.
authors.forename: E
authors.initials: E
authors.lastname: Orta-Salazar
authors.affiliation: Instituto de Neurobiología (INB), Campus UNAM-Juriquilla Qro, CP 76230, México.
authors.forename: A
authors.initials: A
authors.lastname: Aguilar-Vázquez
authors.affiliation: University of CA, Irvine Campus, USA.
authors.forename: H
authors.initials: H
authors.lastname: Martínez-Coria
authors.affiliation: Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jal. CP 44340, México.
authors.forename: S
authors.initials: S
authors.lastname: Luquín-De Anda
authors.affiliation: Centro Universitario de Ciencias Biológicas y Agropecuarias, Universidad de Guadalajara, Zapopan, Jal. CP 45110, México.
authors.forename: M
authors.initials: M
authors.lastname: Rivera-Cervantes
authors.affiliation: Centro Universitario de Ciencias Biológicas y Agropecuarias, Universidad de Guadalajara, Zapopan, Jal. CP 45110, México.
authors.forename: C
authors.initials: C
authors.lastname: Beas-Zarate
authors.affiliation: Centro Universitario de Ciencias Biológicas y Agropecuarias, Universidad de Guadalajara, Zapopan, Jal. CP 45110, México.
authors.forename: A
authors.initials: A
authors.lastname: Feria-Velasco
authors.affiliation: Instituto de Neurobiología (INB), Campus UNAM-Juriquilla Qro, CP 76230, México. Electronic address: yoldi@unam.mx.
authors.forename: S
authors.initials: S
authors.lastname: Díaz-Cintra
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000503:physiopathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D002795:Choline O-Acetyltransferase / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000473:pathology*; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019579:Neocortex / Q000473:pathology*; D053764:Presenilin-1 / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics*; D016875:tau Proteins / Q000235:genetics; D000099229:RE1-Silencing Transcription Factor
chemical_list: D016564:Amyloid beta-Protein Precursor; D002795:Choline O-Acetyltransferase; D053764:Presenilin-1; D012097:Repressor Proteins; D016875:tau Proteins; D000099229:RE1-Silencing Transcription Factor
keywords: Alzheimer's disease; Choline acetyltransferase; Hippocampus; NRSF; Neocortex; REST; Transgenic mouse