Article / Research Square
Dose-Dependent Role of a New Biotin Compound in Hippocampal Demyelination in Rats
Burak Yulug,Ertugrul Kilic, Cemal Orhan, Besir Er, Mehmet Tuzcu, Ibrahim Hanifi Ozercan, Nurhan Sahin, Sinan Canpolat, James Komorowski, Sara Perez Ojalvo,
Sarah Sylla, Seyda Cankaya, Kazim Sahin
Abstract
Demyelination is generally observed in different neurodegenerative disorders, including Multiple sclerosis (MS). It is known that high-dose biotin supplementation stabilizes MS progression. To reduce the effective dose of biotin, here we synthesized a new and superior form of biotin, which is a complex of magnesium ionically bound to biotin (MgB) and compared its dose-dependent effect with biotin alone after lysolecithin (LPC)-induced demyelination in rats. Myelination was studied with luxol fast blue staining and revealed that the most significant remyelination occurred in the MgB groups. We observed dose-dependent improved spatial memory in both biotin and MgB combined animals. Furthermore, we detected decreased inflammatory proteins in both treatment groups, which were more prominent in high-dose MgB treated animals, associated with improved NF-κB, OP, and MMP-9 proteins. We further analyzed biotin-related proteins and observed that both biotin and particularly MgB reverses the LPC-induced reduction of these proteins. Furthermore, we have observed that biotin but particularly MgB improves neuronal transmission proteins, Synapsin-1, PSD-93, and PSD 95. Moreover, increased BDNF, GAP-43, and ICAM were detected in both treatment groups, especially significant in high-dose MgB treated animals. Increased GFAP, which indicates reactive gliosis, was observed in LPC treated animals, which were reversed particularly by high-dose MgB treatment. The present data reveal the dose-dependent beneficial effect of biotin on demyelination processes. However, a combination of biotin with Mg resulted in a more potent effect than biotin alone. The robust impact of MgB encourages proof-of-concept studies with MgB in human MS patients.