/manager/Index ${session.getAttribute("locale")} 5 Hepatic iron loading in mice increases cholesterol biosynthesis /manager/Repository/uon:10663 Sat 24 Mar 2018 08:12:41 AEDT ]]> Brain transcriptome perturbations in the Hfe<sup>-/-</sup> mouse model of genetic iron loading /manager/Repository/uon:21833 HFE gene. There is evidence from both human and animal studies that HFE gene variants may affect brain function and modify risks of brain disease. To investigate how disruption of HFE influences brain transcript levels, we used microarray and real-time reverse transcription polymerase chain reaction to assess the brain transcriptome in Hfe−/− mice relative to wildtype AKR controls (age 10 weeks, n ≥ 4/group). The Hfe−/− mouse brain showed numerous significant changes in transcript levels (p < 0.05) although few of these related to proteins directly involved in iron homeostasis. There were robust changes of at least 2-fold in levels of transcripts for prominent genes relating to transcriptional regulation (FBJ osteosarcoma oncogene Fos, early growth response genes), neurotransmission (glutamate NMDA receptor Grin1, GABA receptor Gabbr1) and synaptic plasticity and memory (calcium/calmodulin-dependent protein kinase IIα Camk2a). As previously reported for dietary iron-supplemented mice, there were altered levels of transcripts for genes linked to neuronal ceroid lipofuscinosis, a disease characterized by excessive lipofuscin deposition. Labile iron is known to enhance lipofuscin generation which may accelerate brain aging. The findings provide evidence that iron loading disorders can considerably perturb levels of transcripts for genes essential for normal brain function and may help explain some of the neurologic signs and symptoms reported in hemochromatosis patients.]]> Sat 24 Mar 2018 07:52:17 AEDT ]]>