Sexually Dimorphic Expression of Reelin in the Brain of a Mouse Model of Alzheimer Disease
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Recent evidence highlights the protective role of reelin against amyloid β (Aβ)-induced synaptic dysfunction and cognitive impairment in Alzheimer disease (AD). In this study, exploiting TgCRND8 mice that overexpress a mutant form of amyloid β precursor protein (AβPP) and display an early onset of AD neuropathological signs, we addressed the question whether changes of reelin expression eventually precede the appearance of Aβ-plaques in a sex-dependent manner. We show that sex-associated and brain region-specific differences in reelin expression appear long before Aβ-plaque formation. However, in spite of a downregulation of reelin expression compared to males, TgCRND8 females display fewer Aβ-plaques, suggesting that additional factors, other than sex and reelin level, influence amyloidosis in this mouse model.
KeywordsTgCRND8 Mouse models of AD Sex-influenced gene expression patterns Aβ-plaques
This study was supported by the EC 7th Framework Program, Grant No. 278486 “Develage” and Ateneo 2014 Sapienza to SS and MTF.
- Chishti MA, Yang DS, Janus C, Phinney AL, Horne P, Pearson J, Strome R, Zuker N, Loukides J, French J et al (2001) Early-onset amyloid deposition and cognitive deficits in transgenic mice expressing a double mutant form of amyloid precursor protein 695. J Biol Chem 276:21562–21570CrossRefPubMedGoogle Scholar
- Paxinos G, Watson C (1998) The mouse brain in stereotaxic coordinates. Academic Press Limited, LondonGoogle Scholar
- Steele JW, Brautigam H, Short JA, Sowa A, Shi M, Yadav A, Weaver CM, Westaway D, Fraser PE, St George-Hyslop PH, Gandy S, Hof PR, Dickstein DL (2014) Early fear memory defects are associated with altered synaptic plasticity and molecular architecture in the TgCRND8 Alzheimer’s disease mouse model. J Comp Neurol 522:2319–2335CrossRefPubMedPubMedCentralGoogle Scholar