Crosstalk between androgen signaling and the chemokine receptor CXCR4:a novel strategy to promote myelin regeneration

Multiple sclerosis(MS)is the most common chronic disease of the central nervous system(CNS)in young adults and represents the first cause of severe handicap,originally non-traumatic(Oh et al.,2018).MS is chara cterized by the infiltration of auto reactive lymphocytes specific to myelin through the blood-brain barrier,which results in the appearance of inflammatory demyelinating lesions caused by the death of the central nervous system myelinating cells,oligodendrocytes(Oh et al.,2018).There is a prevalence sexual with a ratio of three times more affected women than men.

Extracellular RNAs-TLR3 signaling contributes to cognitive impairment after chronic neuropathic pain in mice

Chronic pain is often associated with cognitive decline,which could influence the quality of the patient’s life.Recent studies have suggested that Toll-like receptor 3(TLR3)is crucial for memory and learning.Nonetheless,the contribution of TLR3 to the pathogenesis of cognitive decline after chronic pain remains unclear.The level of TLR3 in hippocampal neurons increased in the chronic constriction injury(CCI)group than in the sham group in this study.Importantly,compared to the wild-type(WT)mice,TLR3 knockout(KO)mice and TLR3-specific neuronal knockdown mice both displayed improved cognitive function,reduced levels of inflammatory cytokines and neuronal apoptosis and attenuated injury to hippocampal neuroplasticity.Notably,extracellular RNAs(exRNAs),specifically double-stranded RNAs(dsRNAs),were increased in the sciatic nerve,serum,and hippocampus after CCI.The co-localization of dsRNA with TLR3 was also increased in hippocampal neurons.And the administration of poly(I:C),a dsRNA analog,elevated the levels of dsRNAs and TLR3 in the hippocampus,exacerbating hippocampus-dependent memory.In additon,the dsRNA/TLR3 inhibitor improved cognitive function after CCI.Together,our findings suggested that exRNAs,particularly dsRNAs,that were present in the condition of chronic neuropathic pain,activated TLR3,initiated downstream inflammatory and apoptotic signaling,caused damage to synaptic plasticity,and contributed to the etiology of cognitive impairment after chronic neuropathic pain.