Neuroprotective effect of apolipoprotein D against human coronavirus OC43-induced encephalitis in mice.
Apolipoprotein D (apoD) is a lipocalin upregulated in the nervous system after injury or pathologies such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. We previously demonstrated that apoD protects against neuropathology by controlling the level of peroxidated lipids. Here, we further investigated the biological function of apoD in a mouse model of acute encephalitis. Our results show that apoD transcript and protein are upregulated during acute encephalitis induced by the human coronavirus OC43 (HCoV-OC43) infection. The apoD upregulation coincides with glial activation, and its expression returns to normal levels when the virus is cleared, concomitantly to a resolved glial reactivity. In addition, the overexpression of human apoD in the neurons of Thy-1/ApoD transgenic mice results in a threefold increase of the number of mice surviving to HCoV-OC43 infection. This increased survival rate is correlated with an upregulated glial activation associated with a limited innate immune response (cytokines, chemokines) and T-cell infiltration into infected brains. Moreover, the protection seems to be associated with a restricted phospholipase A2 activity. These data reveal a role for apoD in the regulation of inflammation and suggest that it protects from HCoV-OC43-induced encephalitis, most likely through the phospholipase A2 signaling pathways.
Laboratoire de Biologie Moléculaire, Département des Sciences Biologiques, and BioMed, Centre de Recherches Biomédicales, Université du Québec à Montréal, Montréal, Québec, Canada.
Sonia
S
Do Carmo
Hélène
H
Jacomy
Pierre J
PJ
Talbot
Eric
E
Rassart
D000208:Acute Disease; D000818:Animals; D053399:Apolipoproteins D / Q000235:genetics / Q000378:metabolism*; D001253:Astrocytes; D002490:Central Nervous System / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D018925:Chemokines / Q000096:biosynthesis; D018352:Coronavirus Infections / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D028962:Coronavirus OC43, Human; D016207:Cytokines / Q000096:biosynthesis; D015536:Down-Regulation; D004660:Encephalitis / Q000517:prevention & control* / Q000821:virology*; D004789:Enzyme Activation; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia; D009457:Neuroglia; D018696:Neuroprotective Agents / Q000378:metabolism*; D054467:Phospholipases A2 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000473:pathology; D018800:Thy-1 Antigens / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D019562:Viral Load
D053399:Apolipoproteins D; D018925:Chemokines; D016207:Cytokines; D018836:Inflammation Mediators; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D018800:Thy-1 Antigens; D054467:Phospholipases A2