Premium
P1‐037: PP1 Regulates the Alternative Splicing of TAU Exon 10 Through Splicing Factor SC35
Author(s) -
Qian Wei,
Wang Weihua,
Liu Huanliang,
Wang Jia,
Liu Fei
Publication year - 2016
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2016.06.784
Subject(s) - exon , sr protein , alternative splicing , rna splicing , phosphorylation , splicing factor , intron , biology , microbiology and biotechnology , genetics , gene , rna
Background:Alzheimer’s disease (AD) is commonly considered a disease of the elderly, however it manifests much earlier in Down syndrome (DS). DS is caused by triplication of chromosome-21, associated with intellectual impairment and early onset dementia. Although a number of factors may contribute to cognitive changes DS, the triplication of the amyloid precursor protein (APP) gene located on chromosome-21 has been a key focus. The Tc1 mouse expresses an almost complete copy of human chromosome-21, but is not functionally trisomic for APP, providing an opportunity to evaluate the contribution of chromosome-21 genes to memory function in the absence of APP-related brain changes. The study had two aims (1) to characterise shortand long-term recognition in Tc1 and Tg2576 mice (a transgenic mouse model of amyloid pathology); (2) evaluate the functional integrity of the network underpinning recognition memoryusing c-fos imaging inTc1mice.Methods: Weused a standard object recognition memory paradigm, followed by immunohistochemistry. Results: Tc1 mice demonstrated impaired short(10-minute) and intact long-term (24-hour) memory for objects; the opposite pattern to that shown by aged Tg2576 mice. In addition, Tc1 mice showed impaired short-term retention of object memory when information was reactivated or retrieved from long-term memory either by representing the objects or the context in which the objects were presented 10 mins (but not 24 hours) before the test phase. The same paradigmwas used to examine the pattern of network activity established by a context reminder cue using c-fos imaging. The results showed that c-fos expression in the perirhinal cortex was significantly reduced in control mice compared to Tc1 mice following a context retrieval cue.Conclusions: The present study showed that Tc1 mice possess a selective deficit in shortbut not long-term recognition memory; a pattern opposite to that shown by Tg2576 mice that over express a human APP mutation. This suggests that aberrant APP processingmaymake a distinctive contribution to intellectual impairment in DS. Furthermore, c-fos analysis suggests that deficits in cortical plasticity, specifically in the perirhinal cortex, may underpin the short-term recognition deficits in Tc1 mice.