{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T01:01:22Z","timestamp":1769302882237,"version":"3.49.0"},"reference-count":78,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T00:00:00Z","timestamp":1733097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Louis A. Faillace Endowed Chair in Psychiatry","award":["MH120876"],"award-info":[{"award-number":["MH120876"]}]},{"name":"Louis A. Faillace Endowed Chair in Psychiatry","award":["MH128771"],"award-info":[{"award-number":["MH128771"]}]},{"name":"Louis A. Faillace Endowed Chair in Psychiatry","award":["BX004758"],"award-info":[{"award-number":["BX004758"]}]},{"name":"Louis A. Faillace Endowed Chair in Psychiatry","award":["IK6BX005235"],"award-info":[{"award-number":["IK6BX005235"]}]},{"name":"Louis A. Faillace Endowed Chair in Psychiatry","award":["BX004256"],"award-info":[{"award-number":["BX004256"]}]},{"name":"Louis A. Faillace Endowed Chair in Psychiatry","award":["BX005853"],"award-info":[{"award-number":["BX005853"]}]},{"name":"Louis A. Faillace Endowed Chair in Psychiatry","award":["RX03958"],"award-info":[{"award-number":["RX03958"]}]},{"name":"US National Institute of Health\/National Institute of Mental Health (NIMH)","award":["MH120876"],"award-info":[{"award-number":["MH120876"]}]},{"name":"US National Institute of Health\/National Institute of Mental Health (NIMH)","award":["MH128771"],"award-info":[{"award-number":["MH128771"]}]},{"name":"US National Institute of Health\/National Institute of Mental Health (NIMH)","award":["BX004758"],"award-info":[{"award-number":["BX004758"]}]},{"name":"US National Institute of Health\/National Institute of Mental Health (NIMH)","award":["IK6BX005235"],"award-info":[{"award-number":["IK6BX005235"]}]},{"name":"US National Institute of Health\/National Institute of Mental Health (NIMH)","award":["BX004256"],"award-info":[{"award-number":["BX004256"]}]},{"name":"US National Institute of Health\/National Institute of Mental Health (NIMH)","award":["BX005853"],"award-info":[{"award-number":["BX005853"]}]},{"name":"US National Institute of Health\/National Institute of Mental Health (NIMH)","award":["RX03958"],"award-info":[{"award-number":["RX03958"]}]},{"name":"Merit Review Award","award":["MH120876"],"award-info":[{"award-number":["MH120876"]}]},{"name":"Merit Review Award","award":["MH128771"],"award-info":[{"award-number":["MH128771"]}]},{"name":"Merit Review Award","award":["BX004758"],"award-info":[{"award-number":["BX004758"]}]},{"name":"Merit Review Award","award":["IK6BX005235"],"award-info":[{"award-number":["IK6BX005235"]}]},{"name":"Merit Review Award","award":["BX004256"],"award-info":[{"award-number":["BX004256"]}]},{"name":"Merit Review Award","award":["BX005853"],"award-info":[{"award-number":["BX005853"]}]},{"name":"Merit Review Award","award":["RX03958"],"award-info":[{"award-number":["RX03958"]}]},{"name":"Department of Veterans Affairs","award":["MH120876"],"award-info":[{"award-number":["MH120876"]}]},{"name":"Department of Veterans Affairs","award":["MH128771"],"award-info":[{"award-number":["MH128771"]}]},{"name":"Department of Veterans Affairs","award":["BX004758"],"award-info":[{"award-number":["BX004758"]}]},{"name":"Department of Veterans Affairs","award":["IK6BX005235"],"award-info":[{"award-number":["IK6BX005235"]}]},{"name":"Department of Veterans Affairs","award":["BX004256"],"award-info":[{"award-number":["BX004256"]}]},{"name":"Department of Veterans Affairs","award":["BX005853"],"award-info":[{"award-number":["BX005853"]}]},{"name":"Department of Veterans Affairs","award":["RX03958"],"award-info":[{"award-number":["RX03958"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/cells13231988","type":"journal-article","created":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T06:58:58Z","timestamp":1733122738000},"page":"1988","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Systemic Administration of a Site-Targeted Complement Inhibitor Attenuates Chronic Stress-Induced Social Behavior Deficits and Neuroinflammation in Mice"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3492-3228","authenticated-orcid":false,"given":"Amit Kumar","family":"Madeshiya","sequence":"first","affiliation":[{"name":"Translational Psychiatry Program, Faillace Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX 77054, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brandi","family":"Quintanilla","sequence":"additional","affiliation":[{"name":"Translational Psychiatry Program, Faillace Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX 77054, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carl","family":"Whitehead","sequence":"additional","affiliation":[{"name":"Translational Psychiatry Program, Faillace Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX 77054, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6281-2122","authenticated-orcid":false,"given":"Stephen","family":"Tomlinson","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA"},{"name":"Ralph Johnson VA Medical Center, Charleston, SC 29401, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anilkumar","family":"Pillai","sequence":"additional","affiliation":[{"name":"Translational Psychiatry Program, Faillace Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX 77054, USA"},{"name":"Research and Development, Charlie Norwood VA Medical Center, Augusta, GA 30904, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/0006-3223(95)00131-X","article-title":"An assessment of cognitive function and mood in chronic fatigue syndrome","volume":"39","author":"Marshall","year":"1996","journal-title":"Biol. 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