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10.1186/s40478-018-0569-2 http://scihub22266oqcxt.onion/10.1186/s40478-018-0569-2 30049279/?report=reader!6062955!30049279     free     free     free Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 261.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 261.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 261.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Acta+Neuropathol+Commun 2018 ; 6 (1): 69 Nephropedia Template TP {{tp|p=30049279|t=2018. ABCA1 haplodeficiency affects the brain transcriptome following traumatic brain injury in mice expressing human APOE isoforms |pdf=|usr=}}{{30049279}} gab.com Text ABCA1 haplodeficiency affects the brain transcriptome following traumatic brain injury in mice expressing human APOE isoforms JO: Acta Neuropathol Commun http://www.kidney.de/pget.php?&tw=1&pmid=30049279 #FOAvip Expression of human Apolipoprotein E (APOE) modulates the inflammatory response in an isoform specific manner, with APOE4 isoform eliciting a stronger pro-inflammatory response, suggesting a possible mechanism for worse outcome following traumatic brain injury (TBI). APOE lipidation and stability is modulated by ATP-binding cassette transporter A1 (ABCA1), a transmembrane protein that transports lipids and cholesterol onto APOE. We examined the impact of Abca1 deficiency and APOE isoform expression on the response to TBI using 3-months-old, human APOE3(+/+) (E3/Abca1(+/+)) and APOE4(+/+) (E4/Abca1(+/+)) targeted replacement mice, and APOE3(+/+) and APOE4(+/+) mice with only one functional copy of the Abca1 gene (E3/Abca1(+/-); E4/Abca1(+/-)). TBI-treated mice received a craniotomy followed by a controlled cortical impact (CCI) brain injury in the left hemisphere; sham-treated mice received the same surgical procedure without the impact. We performed RNA-seq using samples from cortices and hippocampi followed by genome-wide differential gene expression analysis. We found that TBI significantly impacted unique transcripts within each group, however, the proportion of unique transcripts was highest in E4/Abca1(+/-) mice. Additionally, we found that Abca1 haplodeficiency increased the expression of microglia sensome genes among only APOE4 injured mice, a response not seen in injured APOE3 mice, nor in either group of sham-treated mice. To identify gene networks, or modules, correlated to TBI, APOE isoform and Abca1 haplodeficiency, we used weighted gene co-expression network analysis (WGCNA). The module that positively correlated to TBI groups was associated with immune response and featured hub genes that were microglia-specific, including Trem2, Tyrobp, Cd68 and Hexb. The modules positively correlated with APOE4 isoform and negatively to Abca1 haplodeficient mice represented "protein translation" and "oxidation-reduction process", respectively. Our results reveal E4/Abca1(+/-) TBI mice have a distinct response to injury, and unique gene networks are associated with APOE isoform, Abca1 insufficiency and injury. Twit Text FOAVip ABCA1 haplodeficiency affects the brain transcriptome following traumatic brain injury in mice expressing human APOE isoforms ????Acta Neuropathol Commun http://www.kidney.de/pget.php?&tw=1&pmid=30049279 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=30049279 #FOAvip English Wikipedia <ref>{{Cite pmid|30049279}}</ref> ABCA1 haplodeficiency affects the brain transcriptome following traumatic brain injury in mice expressing human APOE isoforms #MMPMID30049279 Castranio EL; Wolfe CM; Nam KN; Letronne F; Fitz NF; Lefterov I; Koldamova R Acta Neuropathol Commun 2018[Jul]; 6 (1): 69 PMID30049279show ga Expression of human Apolipoprotein E (APOE) modulates the inflammatory response in an isoform specific manner, with APOE4 isoform eliciting a stronger pro-inflammatory response, suggesting a possible mechanism for worse outcome following traumatic brain injury (TBI). APOE lipidation and stability is modulated by ATP-binding cassette transporter A1 (ABCA1), a transmembrane protein that transports lipids and cholesterol onto APOE. We examined the impact of Abca1 deficiency and APOE isoform expression on the response to TBI using 3-months-old, human APOE3(+/+) (E3/Abca1(+/+)) and APOE4(+/+) (E4/Abca1(+/+)) targeted replacement mice, and APOE3(+/+) and APOE4(+/+) mice with only one functional copy of the Abca1 gene (E3/Abca1(+/-); E4/Abca1(+/-)). TBI-treated mice received a craniotomy followed by a controlled cortical impact (CCI) brain injury in the left hemisphere; sham-treated mice received the same surgical procedure without the impact. We performed RNA-seq using samples from cortices and hippocampi followed by genome-wide differential gene expression analysis. We found that TBI significantly impacted unique transcripts within each group, however, the proportion of unique transcripts was highest in E4/Abca1(+/-) mice. Additionally, we found that Abca1 haplodeficiency increased the expression of microglia sensome genes among only APOE4 injured mice, a response not seen in injured APOE3 mice, nor in either group of sham-treated mice. To identify gene networks, or modules, correlated to TBI, APOE isoform and Abca1 haplodeficiency, we used weighted gene co-expression network analysis (WGCNA). The module that positively correlated to TBI groups was associated with immune response and featured hub genes that were microglia-specific, including Trem2, Tyrobp, Cd68 and Hexb. The modules positively correlated with APOE4 isoform and negatively to Abca1 haplodeficient mice represented "protein translation" and "oxidation-reduction process", respectively. Our results reveal E4/Abca1(+/-) TBI mice have a distinct response to injury, and unique gene networks are associated with APOE isoform, Abca1 insufficiency and injury. |ATP Binding Cassette Transporter 1/*deficiency/genetics[MESH] |Animals[MESH] |Apolipoproteins E/genetics/*metabolism[MESH] |Brain Injuries, Traumatic/*genetics/metabolism/*pathology[MESH] |Brain/*metabolism[MESH] |Disease Models, Animal[MESH] |Gene Expression Regulation/*genetics[MESH] |Gene Regulatory Networks[MESH] |Humans[MESH] |Mice[MESH] |Mice, Inbred C57BL[MESH] |Mice, Transgenic[MESH] |Microglia/metabolism[MESH] |Protein Isoforms/genetics/metabolism[MESH]ABCA1 haplodeficiency affects the brain transcriptome following trauma(epmc).pdf DeepDyve Pubget Overpricing