Specific age-related molecular alterations in the cerebellum of Down syndrome mouse models.
Down syndrome, or trisomy 21, has been modeled with various trisomic and transgenic mice to help understand the consequences of an altered gene dosage in brain development and function. Though Down syndrome has been associated with premature aging, little is known about the molecular and cellular alterations that target brain function. To help identify alterations at specific ages, we analyzed the cerebellum of Ts1Cje mice, trisomic for 77 HSA21 orthologs, at three ages-young (4 months), middle-age (12 months), and old (17 months)-compared to age-matched controls. Quantification of neuronal and glial markers (n=11) revealed increases in GFAP, with an age effect, and S100B, with age and genotype effects. The genotype effect on S100B with age was unexpected as Ts1Cje has only two copies of the S100b gene. Interestingly, the different increase in GFAP observed between Ts1Cje (trisomic segment includes Pcp4 gene) and controls was magnified in TgPCP4 mice (1 extra copy of the human PCP4 gene) at the same age. S100B increase was not found in the TgPCP4 confirming a difference of regulation with aging for GFAP and S100B and excluding the calcium signaling regulator, Pcp4, as a potential candidate for increase of S100B in the Ts1Cje. To understand these differences, comparison of GFAP and S100B immunostainings at young and middle-age were performed. Immunohistochemical detection of differences in GFAP and S100B localization with aging implicate S100B+ oligodendrocytes as a new phenotypic target in this specific aging process.
Univ Paris Diderot, Sorbonne Paris Cité, Unité de Biologie Fonctionnelle et Adaptative, UMR8251, CNRS, Paris, France. Electronic address: creau@univ-paris-diderot.fr.
Nicole
N
Créau
Univ Paris Diderot, Sorbonne Paris Cité, Unité de Biologie Fonctionnelle et Adaptative, UMR8251, CNRS, Paris, France.
Eva
E
Cabet
Univ Paris Diderot, Sorbonne Paris Cité, Unité de Biologie Fonctionnelle et Adaptative, UMR8251, CNRS, Paris, France.
Fabrice
F
Daubigney
Univ Paris Diderot, Sorbonne Paris Cité, Unité de Biologie Fonctionnelle et Adaptative, UMR8251, CNRS, Paris, France.
Benoit
B
Souchet
Univ Paris Diderot, Sorbonne Paris Cité, Unité de Biologie Fonctionnelle et Adaptative, UMR8251, CNRS, Paris, France.
Soumia
S
Bennaï
Univ Paris Diderot, Sorbonne Paris Cité, Unité de Biologie Fonctionnelle et Adaptative, UMR8251, CNRS, Paris, France.
Jean
J
Delabar
D000375:Aging; D000818:Animals; D002531:Cerebellum / Q000254:growth & development / Q000378:metabolism*; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000235:genetics / Q000378:metabolism*; D018628:Gene Dosage; D018507:Gene Expression Regulation, Developmental; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D064568:S100 Calcium Binding Protein beta Subunit / Q000378:metabolism; D014314:Trisomy; D054875:Ubiquitination; D000097603:Dyrk Kinases
D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D064568:S100 Calcium Binding Protein beta Subunit; D000097603:Dyrk Kinases; C489091:Pcp4 protein, mouse; C579159:S100b protein, mouse; C528900:glial fibrillary astrocytic protein, mouse
Aging; Cerebellum; Down syndrome; S100B; Ts1Cje