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

• Main Authors: Grzegorz A. Czapski, Yuhai Zhao, Walter J. Lukiw, Joanna B. Strosznajder
• Format: Article
• Language: English
• Published: MDPI AG 2020-10-01
• Series: International Journal of Molecular Sciences
• Subjects: lipopolysaccharide; systemic inflammation; hippocampus; neuroinflammation; neurodegeneration; microarray
• Online Access: https://www.mdpi.com/1422-0067/21/21/7838

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 <i>Lcn2</i> for Lipocalin 2 (FC = 237.8), involved in glia neurotoxicity. The expression of genes coding proteins involved in epigenetic regulation, histone deacetylases (<i>Hdac4</i>,<i>5</i>,<i>8</i>,<i>9</i>,<i>11</i>) and bromo- and extraterminal domain protein <i>Brd3</i> were downregulated; however, <i>Brd2</i> was found to be upregulated. Remarkably, the significant increase in expression of <i>Lcn2</i>, <i>S100a8</i>, <i>S100a9</i> and also <i>Saa3</i> and <i>Ch25h</i>, was found in AD brains suggesting that early changes of immune-response genes evoked by mild SIR could be crucial in AD pathogenesis.