Orexin cell transplant reduces behavioral arrest severity in narcoleptic mice.

Brain Research
Ana Clementina Equihua-BenítezRené Drucker-Colín

Abstract

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...Continue Reading

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