Myelin restoration by antisense modulation of HuR and HuD ELAV RNA binding protein expression in mouse models of multiple sclerosis

Abstract

Neuropathic pain is the most difficult to treat pain syndrome in multiple sclerosis. Evidence relates neuropathic pain to demyelination that often originates from unresolved neuroinflammation or altered immune response. Post–transcriptional regulation of gene expression might play a fundamental role in the regulation of these processes and the aim of this study was to investigate ELAV RNA binding proteins in demyelination-associated neuropathic pain states. The ubiquitous HuR and the neuronal HuD are involved in inflammatory phenomena and neuronal development and maintenance, respectively. Thus, we investigated their role in the mouse experimental autoimmune encephalomyelitis (EAE) model. HuR resulted overexpressed in the spinal cord of MOG–EAE and PLP–EAE mice and was detected in CD11b+ cells. Intranasal delivery of an antisense oligonucleotide (ASO) to knockdown HuR increased myelin basic protein expression and Luxol Fast Blue staining, indication of increased myelin content, in both EAE models. These effects temporally coincided with attenuation of pain hypersensitivity. Conversely to HuR, HuD was largely downregulated in the MOG-EAE spinal cord, along with GAP43 and Neurofilament H, while in PLP-EAE mice HuD and neuronal markers remained unaltered. In MOG-EAE mice anti–HuR ASO increased the expression of HuD in GAP43 expressing cells and promoted a HuD–mediated neuroprotective activity. In PLP-EAE mice HuR silencing dampened pro–inflammatory response mediated by spinal microglia activation. In conclusion, anti–HuR ASO showed myelin protection at analgesic doses with multitarget mechanisms, and it deserves further consideration as an innovative agent to counteract demyelination in neuropathic pain states.

Indonesian Indonesian Medicine Plants for Mental Health Disorders: Anxiety and Depression

“…Based on Table S1, two plants of the Annonaceae family can overcome anxiety, namely Annona muricata and Cananga odorata (Lam.) Hook f. & Thomson) (Samuel et al, 2018;Ohemeng et al, 2020;Borgonetti et al, 2022). Part used is in the form of leaves, bark, and flowers.…”

“…Volume 35 Issue 1 (2024) The essential oil from ylang flowers has a relatively high anxiolytic activity compared to others at a dose of 30 mg/kg (Borgonetti et al 2022). In Table S2 The Arecaceae family in Table S3 also contains three plants with the potential to overcome mental health disorders, Areca catechu L., Salacca zalacca, and Cocos nucifera L. (Mansour et al, 2021;Fahrudin & Haribowo, 2021;Azis & Rinding Lawan, 2020).…”