Orexin cell transplant reduces behavioral arrest severity in narcoleptic mice
Por:
Clementina Equihua-Benitez, Ana, Equihua-Benitez, Julian A., Guzman-Vasquez, Khalil, Prospero-Garcia, Oscar, Drucker-Colin, Rene
Publicada:
15 oct 2020
Resumen:
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.
Filiaciones:
Clementina Equihua-Benitez, Ana:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Dept Neuropatol Mol, Circuito Exterior S-N,Ciudad Univ, Ciudad De Mexico 04510, Mexico
Equihua-Benitez, Julian A.:
Consejo Nacl Conocimiento & Uso Biodiversidad, Direcc Gen Proyectos Interinst, Insurgentes Sur 4903,Parques Pedregal, Ciudad De Mexico 14010, Mexico
Guzman-Vasquez, Khalil:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Dept Neuropatol Mol, Circuito Exterior S-N,Ciudad Univ, Ciudad De Mexico 04510, Mexico
Prospero-Garcia, Oscar:
Univ Nacl Autonoma Mexico, Fac Med, Dept Fisiol, Lab Cannabinoides, Ciudad Univ, Ciudad De Mexico 04510, Mexico
Drucker-Colin, Rene:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Dept Neuropatol Mol, Circuito Exterior S-N,Ciudad Univ, Ciudad De Mexico 04510, Mexico
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