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Global gene expression changes in the aged mouse cerebellum
Author(s) -
Rotter Andrej,
Popesco Magdalena,
Frostholm Adrienne
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1041
Subject(s) - acyltransferase , cerebellum , gene expression , biology , gene , biochemistry , medicine , endocrinology
Impaired motor coordination and balance during senescence may result from modifications in specific cerebellar pathways. Serial Analysis of Gene Expression (SAGE) was used to assess aging‐related gene expression changes in the cerebellum of 3 adult and 3 aged mice. Combined unique tags for each group revealed 325 differentially expressed genes (P‐chance, <0.05). Four additional tests (mixed effect model, t‐test, Wilcoxon rank‐sum and z‐test) were used to reduce the likelihood of false positives. Twenty‐nine genes were found to be differentially expressed by at least two of the four tests. Several of these coded for key enzymes in the glycerophospholipid metabolic network (Agps, alkyl glycerone phosphate synthase; Agpat, 1‐acyl‐sn‐glycerol 3‐phosphate acyltransferase; and Dgkz, diacyl glycerol kinase zeta). Notably, all four statistical tests showed that the expression of a single gene, Agps, decreased in the aged cerebellum. P‐chance analysis detected increased expression of two additional members of the glycerophospholipid pathway, Pla2g4b, (phospholipase A2, group IVB) and Gpam (glycerol‐3‐phosphate acyltransferase). Our data suggest that functional decrements during senescence may result, at least in part, from a cascade of biochemical events leading to defective myelination and impaired conduction in cerebellar neurons. Supported by NIH Grants AG021698 and AA014422 (AR)