Abstract
Multiple sclerosis (MS) is a chronic condition characterized by immune cell infiltration and cytokine overproduction that led to myelin sheath inflammatory assaults, thus causing axonal destruction. The former consequently provokes motor impairment and psychological disorders. Markedly, depression is one of the most prevalent lifelong comorbidities that negatively impacts the quality of life in MS patients. Vortioxetine (VTX), a multi-modal molecule prescribed to manage depression and anxiety disorder, additionally, it displays a promising neuroprotective properties against neurodegenerative diseases such as Alzheimer's and Parkinson's. To this end, the present study investigated the potential therapeutic efficacy of VTX against experimental autoimmune encephalomyelitis (EAE) model of MS in mice.Notably, treatment with VTX significantly ameliorated EAE-induced motor disability, as evident by enhanced performance in open field, rotarod and grip strength tests, alongside a reduction in immobility time during the forced swimming test, indicating a mitigation of the depressive-like behavior; outcomes that were corroborated with histological examinations and biochemical analyses. Mechanistically, VTX enhanced serotonin levels by inhibiting both serotonin transporter (SERT) and indoleamine 2,3-dioxygenase (IDO) enzyme, thereby promoting the activation of serotonin 1A (5-HT1A) receptor. The latter triggered the stimulation of phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) cascade that entailed activation/phosphorylation of cAMP response element-binding protein (CREB). This activation increased brain derived neurotrophic factor (BDNF) and myelin basic protein (MBP) contents that mitigated demyelination in the corpus callosum. Furthermore, VTX suppressed phospho serine 536 nuclear factor kappa B (pS536 NF-κB p65) activity and reduced tumor necrosis factor-alpha (TNF-α) production. The results underscore VTX's beneficial effects on disease severity in EAE model of MS in mice by amending both inflammatory and neurodegenerative components of MS progression.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
