Systemic Administration of a Site-Targeted Complement Inhibitor Attenuates Chronic Stress-Induced Social Behavior Deficits and Neuroinflammation in Mice

Authors

Amit Kumar Madeshiya
Brandi Quintanilla
Carl Whitehead
Stephen Tomlinson
Anilkumar Pillai

Language

English

Publication Date

12-2-2024

Journal

Cells

DOI

10.3390/cells13231988

PMID

39682736

PMCID

PMC11640647

PubMedCentral® Posted Date

12-2-2024

PubMedCentral® Full Text Version

Post-print

Abstract

Chronic stress, a risk factor for many neuropsychiatric conditions, causes dysregulation in the immune system in both humans and animal models. Additionally, inflammation and synapse loss have been associated with deficits in social behavior. The complement system, a key player of innate immunity, has been linked to social behavior impairments caused by chronic stress. However, it is not known whether complement inhibition can help prevent neuroinflammation and behavioral deficits caused by chronic stress. In this study, we investigated the potential of a site-targeted complement inhibitor to ameliorate chronic stress-induced changes in social behavior and inflammatory markers in the prefrontal cortex (PFC) and hippocampus. Specifically, we investigated the use of C2-Crry, which comprises a natural antibody-derived single-chain antibody (ScFv) targeting domain-designated C2, linked to Crry, a C3 activation inhibitor. The C2 targeting domain recognizes danger-associated molecular patterns consisting of a subset of phospholipids that become exposed following cell stress or injury. We found that systemic administration of C2-Crry attenuated chronic stress-induced social behavioral impairments in mice. Furthermore, C2-Crry administration significantly decreased microglia/macrophage and astrocyte activation markers in the PFC and hippocampus. These findings suggest that site-targeted complement inhibition could offer a promising, safe, and effective strategy for treating chronic stress induced behavioral and immune function disorders.

Keywords

Animals, Mice, Stress, Psychological, Male, Social Behavior, Mice, Inbred C57BL, Neuroinflammatory Diseases, Prefrontal Cortex, Hippocampus, Complement Inactivating Agents, Microglia, Single-Chain Antibodies, Behavior, Animal, Inflammation, ID: PMC11640647

Published Open-Access

yes

Recommended Citation

Madeshiya, Amit Kumar; Quintanilla, Brandi; Whitehead, Carl; et al., "Systemic Administration of a Site-Targeted Complement Inhibitor Attenuates Chronic Stress-Induced Social Behavior Deficits and Neuroinflammation in Mice" (2024). Faculty, Staff and Student Publications. 6428.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6428