β-Hydroxybutyrate Diminishes the Apoptotic Cell Death and Demyelination via Altering Bax, Caspase-3, and Bcl2 Levels in the Spinal Cord of Mice with MOG-Induced Encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) model has been used to investigate the mechanisms by which β-hydroxybutyrate treatment contributes to reduced the demyelination and apoptosis in multiple sclerosis (MS). The present study aimed to examin whether β-hydroxybutyrate, the most abundant ketone body metabolite, can diminish demyelination and axonal damage in the spinal cord. To do this, thirty female C57BL/6 mice were divided into three experimental groups including control, EAE, and EAE + β-hydroxybutyrate. After the EAE clinical symptoms started, the mice were treated with β‑hydroxybutyrate for 9 consecutive days. Then, the mice were sacrificed and the spinal cord was extruded and the apoptotic cell death by the TUNEL (Terminal deoxynucleotidyl transferase dUTP Nick End Lebeling) method and the levels of Bax, caspase-3 and Bcl2 (markers of apoptosis activation) were assessed. We also evaluated the demyelination of neurons in the spinal cord of EAE-induced mice following β‑hydroxybutyrate treatment. The findings showed that β-hydroxybutyrate treatment effectively diminished the apoptosis process by decreasing Bax and caspase-3 levels and increasing Bcl2 level in the spinal cord of EAE-induced mice. It also alleviated the demyelination of neurons in the spinal cord of EAE-induced mice. This study suggests that β-hydroxybutyrate treatment might be involved in the pathology of EAE disease, and could be used as a therapeutic candidate for future studies.