NEUROLOGICAL SCIENCES AND NEUROPHYSIOLOGY, vol.37, no.3, pp.118-123, 2020 (SCI-Expanded)
Objective: Anti-neuronal antibodies are found in sera of neuro-Behçet’s
disease (NBD) patients. In this study, our aim was to analyze the potential
mechanisms by which NBD immunoglobulin (Ig) Gs affect neuronal
dysfunction. Materials and Methods: Purified IgGs obtained from pooled
sera of six each NBD patients and healthy controls (HCs) were administered
to Sprague Dawley rats through intraventricular injection. Control rats received
phosphate-buffered saline (PBS) only. Locomotor activity was assessed by
open field test on days 0, 10, and 25. Cerebral expression levels of intracellular
pathway factors associated with cell survival and viability were measured by
real-time polymerase chain reaction. Results: Rats treated with NBD IgG
exhibited reduced motor activity. On day 25, the mean number of crossings was
44 ± 7, 90 ± 12, and 93 ± 5 and the mean number of rearings was 18 ± 7,
34 ± 5, and 35 ± 6 for NBD IgG, HC IgG, and PBS groups, respectively
(P < 0.001). Relative expression levels of Akt-1 (0.4 ± 0.2, 1.0 ± 0.3, and
0.9 ± 0.6; P = 0.004), DJ-1 (0.6 ± 0.2, 1.0 ± 0.6, and 0.9 ± 0.5; P = 0.047),
mouse double mininute-2 (0.5 ± 0.3, 0.9 ± 0.2, and 1.0 ± 0.2; P = 0.002), and
mechanistic target of rapamycin (0.4 ± 0.2, 0.8 ± 0.4, and 0.9 ± 0.6; P = 0.006)
were significantly lower in NBD-IgG group than HC IgG and PBS groups. By
contrast, the expression levels of factors associated with apoptosis (caspase 3,
mitochondrial carrier homolog 1, and B-cell lymphoma-2) were comparable
among different treatment arms. Conclusion: Our results suggest that at least a
fraction of NBD IgG interacts with neuronal surface antigens and subsequently
decreases neuronal viability through Akt pathway inhibition. By contrast, NBD
IgG does not appear to activate neuronal apoptosis. Further identification of the
binding sites of serum IgG ıs required.