Narcolepsy is a sleep disorder that has been associated with the loss of orexinergic neurons from the lateral hypothalamic area. This loss leads to dysregulated sleep and cataplexy attacks. Therapeutic options are currently limited to symptom management with pharmacotherapy and nonpharmacological approaches. Nonetheless, cell replacement therapy could offer relief, and research in the field has yielded positive results for other neurodegenerative disorders, such as Parkinson’s disease. Thus, we propose that orexin cell rich grafts could help improve narcoleptic symptoms in the orexin/ataxin-3 mouse model of narcolepsy. For this purpose, we isolated EGFP+ cells from either orexin/EGFP or CAG-EGFP mice with the use of a flow cytometer and grafted them into the pedunculopontine and laterodorsal tegmentum nuclei (PPT/LDDT) of orexin/ataxin-3 mice. Our results show that even small orexinergic grafts can reduce the severity of behavioral arrests, with a median reduction of 30.31% in episode duration, 51.35% for number of events and 69.73% in time spent in the behavioral arrest state and help with sleep fragmentation measured in number of bouts per behavioral state. Surprisingly, control grafts made from cerebellar tissue also reduced behavioral arrest severity, but to a lesser degree. Although still at a very early stage, these results show that there is potential in cell grafts for improving aspects of the narcoleptic phenotype and further research could help elucidate realistic expectations of an orexin cell replacement therapy for narcolepsy.

发作性睡病是一种睡眠障碍，与下丘脑外侧区的食欲神经元丢失有关。这种损失会导致睡眠失调和猝倒发作。治疗选择目前仅限于通过药物治疗和非药物方法进行症状管理。尽管如此，细胞替代疗法可以提供缓解，并且该领域的研究已经对其他神经退行性疾病（如帕金森病）产生了积极的结果。因此，我们提出富含orexin 细胞的移植物有助于改善orexin/ataxin-3 发作性睡病小鼠模型中的发作性睡病症状。为此，我们使用流式细胞仪从 orexin/EGFP 或 CAG-EGFP 小鼠中分离出 EGFP+ 细胞，并将它们移植到 orexin/ataxin-3 小鼠的脚桥和侧背被盖核 (PPT/LDDT) 中。我们的结果表明，即使是小的食欲能移植物也可以降低行为停滞的严重程度，发作持续时间中位数减少 30.31%，事件数量减少 51.35%，行为停滞状态时间减少 69.73%，并有助于测量睡眠碎片每种行为状态的回合数。令人惊讶的是，由小脑组织制成的对照移植物也降低了行为停滞的严重程度，但程度较轻。尽管仍处于非常早期的阶段，但这些结果表明，细胞移植有改善发作性睡病表型方面的潜力，进一步的研究可能有助于阐明对发作性睡病的食欲素细胞替代疗法的现实期望。51.35% 的事件数量和 69.73% 的时间花费在行为停滞状态并帮助睡眠碎片化，以每种行为状态的发作次数衡量。令人惊讶的是，由小脑组织制成的对照移植物也降低了行为停滞的严重程度，但程度较轻。尽管仍处于非常早期的阶段，但这些结果表明，细胞移植有改善发作性睡病表型方面的潜力，进一步的研究可能有助于阐明对发作性睡病的食欲素细胞替代疗法的现实期望。51.35% 的事件数量和 69.73% 的时间花费在行为停滞状态并帮助睡眠碎片化，以每种行为状态的发作次数衡量。令人惊讶的是，由小脑组织制成的对照移植物也降低了行为停滞的严重程度，但程度较轻。尽管仍处于非常早期的阶段，但这些结果表明，细胞移植有改善发作性睡病表型方面的潜力，进一步的研究可能有助于阐明对发作性睡病的食欲素细胞替代疗法的现实期望。