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Plasma Autoantibodies from Human Diabetic Depression Patients Inhibit Neuritogenesis and Induce Depression‐Like Behavior in Mice
Author(s) -
Behnke Joseph,
Alder Janet,
ThakkerVaria Smita,
Zimering Mark
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.704.8
Subject(s) - endocrinology , medicine , autoantibody , depression (economics) , hippocampal formation , diabetes mellitus , mood , type 1 diabetes , pathophysiology , immunology , antibody , psychiatry , economics , macroeconomics
Type 2 diabetes mellitus (DM) substantially increases susceptibility to the affective mood disorder depression. However, the underlying mechanism for this association is unclear. Previous studies demonstrated significant associations between autoantibodies (AB) that inhibit neuronal and endothelial function and specific diabetic microvascular complications. In the current study, we tested the hypothesis that diabetic depression AB affect hippocampal neuritogenesis and induce a depression‐like phenotype in mice. Diabetic depression AB significantly inhibited bFGF‐stimulated PC12 cell process outgrowth (n=12; P<0.001), and hippocampal culture neuritogenesis (n=4; P<0.01) compared to diabetic, no depression AB (n=20) or no AB (n=2), respectively. Diabetic depression AB‐mediated inhibition of hippocampal neuritogenesis was significantly (P<0.01) prevented by Y27632, a selective Rho kinase inhibitor (10 µM). Mice (n=16 in each subgroup) given a single intracerebroventricular infusion of diabetic depression plasma AB (4 µg/mL) isolated from two different patients exhibited a depressive‐like behavioral phenotype, as indicated by a reduced preference for sucrose (P<0.027) compared to mice administered AB (4 ug/mL) from two non‐depressed diabetic patients. These data suggest a possible causal role for autoantibodies which can inhibit hippocampal neuritogenesis in depression in older adult type 2 DM.