CD46 expression in the central nervous system of male and female pubescent mice

Pasquale Esposito; Cloudia Rodriguez; Michelle Gandelman; Jacky Liang; Nafissa Ismail

doi:10.1016/j.jneuroim.2023.578234

CD46 expression in the central nervous system of male and female pubescent mice

J Neuroimmunol. 2023 Dec 15:385:578234. doi: 10.1016/j.jneuroim.2023.578234. Epub 2023 Nov 4.

Authors

Pasquale Esposito¹, Cloudia Rodriguez¹, Michelle Gandelman¹, Jacky Liang¹, Nafissa Ismail²

Affiliations

¹ Neuroimmunology, Stress, and Endocrinology (NISE) Laboratory, University of Ottawa, Ottawa, ON K1N 6N5, Canada.
² Neuroimmunology, Stress, and Endocrinology (NISE) Laboratory, University of Ottawa, Ottawa, ON K1N 6N5, Canada; LIFE Research Institute, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada; Brain and Mind Research Institute, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada. Electronic address: nafissa.ismail@uottawa.ca.

PMID: 37944208
DOI: 10.1016/j.jneuroim.2023.578234

Abstract

CD46 is a complementary regulatory protein ubiquitously expressed in human cells, controlling complement system activation. CD46 has further been identified to have several other functions including regulatory T cell induction and intestinal epithelial (IEC) barrier regulation. Activation of CD46 in the IEC can impact intestinal barrier permeability and immune system functioning. CD46 has only been identified in the spermatozoa and retina of mice. In other murine cells, the homologue CRRY is identified to function as the complementary regulator. Due to the identification of CRRY across other wild-type mouse cells and the development of mouse strains transgenic for human CD46, no recent research has been conducted to determine if CD46 is present in non-transgenic mouse strains. Therefore, the current study investigated if CD46 is expressed in the substantia nigra (SN) and caudate putamen (CP) of pubescent CD1 mice and examined the acute effects of pubertal antimicrobial and lipopolysaccharide (LPS) treatment on CD46 expression in the brain. As of 5 weeks of age, mice were administered mixed antimicrobial solution or water with oral gavage twice daily for 7 days. At 6 weeks of age, mice received an intraperitoneal injection of LPS or saline. Mice were euthanized 8 h post-injection and brain samples were collected. Our results indicate that pubescent CD-1 mice express CD46 in the SN and CP. However, LPS-treated mice displayed significantly less CD46 expression in the SN in comparison to saline-treated mice. Furthermore, males displayed more CD46 in the CP compared to females, regardless of LPS and antimicrobial treatments. Our data suggest CD46 is present in CD1 mice and that LPS and antimicrobial treatments impact CD46 protein expression in a sex-dependent manner. These results have important implications for the expression of CD46 in the mouse brain and the understanding of its role in immune system regulation.

Keywords: Brain; Gut Dysbiosis; Immune system; Inflammation; Puberty; Sex difference.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Infective Agents / pharmacology
Brain* / metabolism
Female
Humans
Infant, Newborn
Lipopolysaccharides / pharmacology
Male
Membrane Cofactor Protein* / genetics
Membrane Cofactor Protein* / metabolism
Membrane Glycoproteins
Mice
Mice, Inbred Strains

Substances

Anti-Infective Agents
Lipopolysaccharides
Membrane Cofactor Protein
Membrane Glycoproteins
Mcp protein, mouse