RESUMEN
Because opioid withdrawal is an intensely aversive experience, persons with opioid use disorder (OUD) often relapse to avoid it. The lateral septum (LS) is a forebrain structure that is important in aversion processing, and previous studies have linked the lateral septum (LS) to substance use disorders. It is unclear, however, which precise LS cell types might contribute to the maladaptive state of withdrawal. To address this, we used single-nucleus RNA-sequencing to interrogate cell type specific gene expression changes induced by chronic morphine and withdrawal. We discovered that morphine globally disrupted the transcriptional profile of LS cell types, but Neurotensin-expressing neurons (Nts; LS-Nts neurons) were selectively activated by naloxone. Using two-photon calcium imaging and ex vivo electrophysiology, we next demonstrate that LS-Nts neurons receive enhanced glutamatergic drive in morphine-dependent mice and remain hyperactivated during opioid withdrawal. Finally, we showed that activating and silencing LS-Nts neurons during opioid withdrawal regulates pain coping behaviors and sociability. Together, these results suggest that LS-Nts neurons are a key neural substrate involved in opioid withdrawal and establish the LS as a crucial regulator of adaptive behaviors, specifically pertaining to OUD.
RESUMEN
Bone tissue engineering (BTE) is based on the participation and combination of different biomaterials, cells, and bioactive molecules to generate biosynthetic grafts for bone regeneration. Electrospinning has been used to fabricate fibrous scaffolds, which provide nanoscale architecture comprising interconnecting pores, resembling the natural hierarchy of tissues and enabling the formation of artificial functional tissues. Electrospun fibers for BTE applications have been mostly produced from polymers (chitosan, alginate, polycaprolactone, polylactic acid) and bioceramics (hydroxyapatite). Stem cells are among the most prolific cell types employed in regenerative medicine owing to their self-renewal and differentiation capacity. Most importantly, bioactive molecules, such as synthetic drugs, growth factors, and phytocompounds, are consistently used to regulate cell behavior inducing differentiation towards the osteoblast lineage. An expanding body of literature has provided evidence that these electrospun fibers loaded with bioactive molecules support the differentiation of stem cells towards osteoblasts. Thus, this review briefly describes the current development of polymers and bioceramic-based electrospun fibers and the influence of bioactive molecules in these electrospun fibers on bone tissue regeneration.
