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10.1016/j.cell.2016.04.001 http://scihub22266oqcxt.onion/10.1016/j.cell.2016.04.001 C4860138!4860138 !27114033     free     free     free Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 263.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 263.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\27114033 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Cell 2016 ; 165 (4 ): 921-35 Nephropedia Template TP {{tp|p=27114033 |t=2016. Progranulin Deficiency Promotes Circuit-Specific Synaptic Pruning by Microglia via Complement Activation |pdf=|usr=}}{{27114033 }} gab.com Text Progranulin Deficiency Promotes Circuit-Specific Synaptic Pruning by Microglia via Complement Activation JO: Cell http://www.kidney.de/pget.php?&tw=1&pmid=27114033 #FOAvip Microglia maintain homeostasis in the brain, but whether aberrant microglial activation can cause neurodegeneration remains controversial. Here, we use transcriptome profiling to demonstrate that deficiency in frontotemporal dementia (FTD) gene progranulin (Grn) leads to an age-dependent, progressive upregulation of lysosomal and innate immunity genes, increased complement production, and enhanced synaptic pruning in microglia. During aging, Grn(-/-) mice show profound microglia infiltration and preferential elimination of inhibitory synapses in the ventral thalamus, which lead to hyperexcitability in the thalamocortical circuits and obsessive-compulsive disorder (OCD)-like grooming behaviors. Remarkably, deleting C1qa gene significantly reduces synaptic pruning by Grn(-/-) microglia and mitigates neurodegeneration, behavioral phenotypes, and premature mortality in Grn(-/-) mice. Together, our results uncover a previously unrecognized role of progranulin in suppressing aberrant microglia activation during aging. These results represent an important conceptual advance that complement activation and microglia-mediated synaptic pruning are major drivers, rather than consequences, of neurodegeneration caused by progranulin deficiency. Twit Text FOAVip Progranulin Deficiency Promotes Circuit-Specific Synaptic Pruning by Microglia via Complement Activation ????Cell http://www.kidney.de/pget.php?&tw=1&pmid=27114033 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=27114033 #FOAvip English Wikipedia <ref>{{Cite pmid|27114033 }}</ref> Progranulin Deficiency Promotes Circuit-Specific Synaptic Pruning by Microglia via Complement Activation #MMPMID27114033 Lui H ; Zhang J ; Makinson SR ; Cahill MK ; Kelley KW ; Huang HY ; Shang Y ; Oldham MC ; Martens LH ; Gao F ; Coppola G ; Sloan SA ; Hsieh CL ; Kim CC ; Bigio EH ; Weintraub S ; Mesulam MM ; Rademakers R ; Mackenzie IR ; Seeley WW ; Karydas A ; Miller BL ; Borroni B ; Ghidoni R ; Farese RV Jr ; Paz JT ; Barres BA ; Huang EJ Cell 2016[May]; 165 (4 ): 921-35 PMID27114033 show ga Microglia maintain homeostasis in the brain, but whether aberrant microglial activation can cause neurodegeneration remains controversial. Here, we use transcriptome profiling to demonstrate that deficiency in frontotemporal dementia (FTD) gene progranulin (Grn) leads to an age-dependent, progressive upregulation of lysosomal and innate immunity genes, increased complement production, and enhanced synaptic pruning in microglia. During aging, Grn(-/-) mice show profound microglia infiltration and preferential elimination of inhibitory synapses in the ventral thalamus, which lead to hyperexcitability in the thalamocortical circuits and obsessive-compulsive disorder (OCD)-like grooming behaviors. Remarkably, deleting C1qa gene significantly reduces synaptic pruning by Grn(-/-) microglia and mitigates neurodegeneration, behavioral phenotypes, and premature mortality in Grn(-/-) mice. Together, our results uncover a previously unrecognized role of progranulin in suppressing aberrant microglia activation during aging. These results represent an important conceptual advance that complement activation and microglia-mediated synaptic pruning are major drivers, rather than consequences, of neurodegeneration caused by progranulin deficiency. |*Complement Activation [MESH] |Aging/immunology/*metabolism [MESH] |Animals [MESH] |Brain/*metabolism [MESH] |Cerebrospinal Fluid [MESH] |Complement C1q/genetics/*metabolism [MESH] |Frontotemporal Dementia/genetics/metabolism [MESH] |Granulins [MESH] |Humans [MESH] |Immunity, Innate [MESH] |Intercellular Signaling Peptides and Proteins/deficiency/genetics/*metabolism [MESH] |Lysosomes/metabolism [MESH] |Metabolic Networks and Pathways [MESH] |Mice [MESH] |Microglia/*metabolism [MESH] |Obsessive-Compulsive Disorder/genetics/metabolism [MESH] |Progranulins [MESH] |Synapses/metabolism [MESH]Progranulin Deficiency Promotes Circuit-Specific Synaptic Pruning by M(epmc).pdf DeepDyve Pubget Overpricing