Acute Systemic Inflammatory Response Alters Transcription Profile of Genes Related to Immune Response and Ca2+ Homeostasis in Hippocampus; Relevance to Neurodegenerative Disorders.

Acute systemic inflammatory response (SIR) triggers an alteration in the transcription of brain genes related to neuroinflammation, oxidative stress and cells death. These changes are also characteristic for Alzheimer's disease (AD) neuropathology. Our aim was to evaluate gene expression patterns in the mouse hippocampus (MH) by using microarray technology 12 and 96 h after SIR evoked by lipopolysaccharide (LPS). The results were compared with microarray analysis of human postmortem hippocampal AD tissues. It was found that 12 h after LPS administration the expression of 231 genes in MH was significantly altered (FC > 2.0); however, after 96 h only the S100a8 gene encoding calgranulin A was activated (FC = 2.9). Gene ontology enrichment analysis demonstrated the alteration of gene expression related mostly to the immune-response including the gene Lcn2 for Lipocalin 2 (FC = 237.8), involved in glia neurotoxicity. The expression of genes coding proteins involved in epigenetic regulation, histone deacetylases (Hdac4,5,8,9,11) and bromo- and extraterminal domain protein Brd3 were downregulated; however, Brd2 was found to be upregulated. Remarkably, the significant increase in expression of Lcn2, S100a8, S100a9 and also Saa3 and Ch25h, was found in AD brains suggesting that early changes of immune-response genes evoked by mild SIR could be crucial in AD pathogenesis.

Smaller genetic risk in catabolic process explains lower energy expenditure, more athletic capability and higher prevalence of obesity in Africans.

Lower energy expenditure (EE) for physical activity was observed in Africans than in Europeans, which might contribute to the higher prevalence of obesity and more athletic capability in Africans. But it is still unclear why EE is lower among African populations. In this study we tried to explore the genetic mechanism underlying lower EE in Africans. We screened 231 common variants with possibly harmful impact on 182 genes in the catabolic process. The genetic risk, including the total number of mutations and the sum of harmful probabilities, was calculated and analyzed for the screened variants at a population level. Results of the genetic risk among human groups showed that most Africans (3 out of 4 groups) had a significantly smaller genetic risk in the catabolic process than Europeans and Asians, which might result in higher efficiency of generating energy among Africans. In sport competitions, athletes need massive amounts of energy expenditure in a short period of time, so higher efficiency of energy generation might help make African-descendent athletes more powerful. On the other hand, higher efficiency of generating energy might also result in consuming smaller volumes of body mass. As a result, Africans might be more vulnerable to obesity compared to the other races when under the same or similar conditions. Therefore, the smaller genetic risk in the catabolic process might be at the core of understanding lower EE, more athletic capability and higher prevalence of obesity in Africans.