title: Aspects of the narcolepsy-cataplexy syndrome in O/E3-null mutant mice.
abstract: Orexins (hypocretins) are peptide neurotransmitters produced by a small group of neurons located exclusively in the lateral hypothalamus (LH). Orexins modulate arousal, and as a result, have profound effects on feeding behavior and the sleep-wake cycle. Loss of orexin producing neurons leads to a narcoleptic phenotype, characterized by sudden transitions from vigilance to rapid eye movement (REM) sleep (direct transition to REM, DREM) observed in electroencephalogram (EEG) and electromyogram (EMG) recordings. In this study, we demonstrate that mice lacking the basic helix-loop-helix transcription factor O/E3 (also known as ebf2) have a decrease in orexin-producing cells in the LH, in addition to a severely impaired orexinergic innervation of the pons. These changes in the orexinergic circuit of O/E3-null animals induce a narcoleptic phenotype, similar to the one arising in orexin-deficient and orexin-ataxin-3 mice. Taken together, our results suggest that O/E3 plays a central role during the establishment of a functional orexinergic circuit by controlling the expression of essential hypothalamic neurotransmitter and the correct development of the nerve fibers arising from the hypothalamus. This is the first report regarding the narcolepsy-cataplexy syndrome in O/E3-null mice, which adds the importance of transcription factors in the regulation of neural subpopulations that control the sleep-wake cycle.
authors: Departamento de Neuropatología Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México Distrito Federal, Mexico.
authors: A K
authors: AK
authors: De La Herrán-Arita
authors: V C
authors: VC
authors: Zomosa-Signoret
authors: D A
authors: DA
authors: Millán-Aldaco
authors: M
authors: M
authors: Palomero-Rivero
authors: M
authors: M
authors: Guerra-Crespo
authors: R
authors: R
authors: Drucker-Colín
authors: R
authors: R
authors: Vidaltamayo
mesh_terms: D000818:Animals; D001143:Arousal / Q000187:drug effects; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency*; D001921:Brain / Q000473:pathology; D002375:Catalepsy; D002452:Cell Count; D002940:Circadian Rhythm / Q000502:physiology; D004195:Disease Models, Animal; D004569:Electroencephalography; D004576:Electromyography; D005786:Gene Expression Regulation / Q000235:genetics; D006168:Guinea Pigs; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009290:Narcolepsy / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism / Q000627:therapeutic use; D018377:Neurotransmitter Agents / Q000627:therapeutic use; D000068797:Orexins; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D000068797:Orexins; D015534:Trans-Activators; C489921:Ebf1 protein, mouse; C489922:Ebf2 protein, mouse