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Cholinesterase activity in brain of senescence‐accelerated‐resistant mouse SAMR1 and its variation in brain of senescence‐accelerated‐prone mouse SAMP8
Author(s) -
FernándezGómez Francisco José,
MuñozDelgado Encarnación,
Montenegro María Fernanda,
Campoy Francisco J.,
Vidal Cecilio J.,
Jordán Joaquín
Publication year - 2010
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22177
Subject(s) - butyrylcholinesterase , acetylcholinesterase , senescence , cholinesterase , endocrinology , glial fibrillary acidic protein , medicine , aché , chemistry , biology , enzyme , biochemistry , immunohistochemistry
The early‐onset, irreversible, severe deficits of learning and memory in the senescence‐accelerated mouse (SAM)‐prone/8 (SAMP8) support its use as an animal model for human dementias of early onset. Possible implication of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in cognitive dysfunction of SAMP8 mice was studied by comparing cholinesterase (ChE) expression in brains of SAMP8 mice and of their normal control, SAM‐resistant/1 (SAMR1) mice. The level of ChE mRNAs was the same in SAMP8 and SAMR1 brains, which agreed with their equal AChE activity (3.09 ± 1.45 vs. 3.07 ± 1.44 μmol·hr −1 ·mg protein −1 , U/mg), but not with a doubled BuChE activity in SAMP8 brain (0.14 ± 0.05 vs. 0.07 ± 0.02 U/mg; P < 0.01). This great increase in neural BuChE activity may contribute to cognitive deficit of SAMP8 mice. Hydrophilic (G 4 H , 8%) and amphiphilic (G 4 A , 74%) AChE tetramers, besides dimers and monomers (G 2 A+ G 1 A , 18%), were identified in SAMR1 brains. They also contained G 4 HBuChE forms (18%) as well as G 4 A(53%) and G 2 A+ G 1 A(29%) species. Although SAMP8 brain displayed proportions of AChE and BuChE forms that were similar to those of SAMR1 brain, phenyl‐agarose chromatography with detergent‐free extracts showed a rise in the proportion of secretory G 4 HBuChE from 35% in SAMR1 to 44% in SAMP8 brain. The strong immunolabelling of glial fibrillary acidic protein (GFAP), a marker of reactive gliosis, in SAMP8 brain and the consideration of BuChE as a marker of glial cells suggest a relationship between phenotypic changes in neuroglial cells and the excess of BuChE activity in SAMP8 brain. © 2009 Wiley‐Liss, Inc.