0428 Taiep Rats Had Normal Levels of Orexin Neurons in the Lateral Hypothalamus But Their Cataplexy Attacks are Sensible to Specific Orexin B Agonist

Abstract

Abstract Introduction Narcolepsy is characterized by sleep fragmentation, sleep paralysis, hypnagogic hallucinations and cataplexy. The cataplexy is a sudden loss of muscle tone triggered by emotions in humans, as well as in animal models. It is stablished that most of the patients had a significant decrease of orexin neurons in the lateral hypothalamus. Taiep rats had a mutation in tubulin TUBB4A and suffer immobility episodes (IE′s) that had a desynchronized activity in the cortex associated with theta rhythm in the hippocampus similar to narcolepsy patients. The aim of this study was to analyze the effects of central administration of an orexin B agonist and determination by immunohistochemistry of the number of orexin neurons on adult male taiep rats. Methods We used 14 male taiep rats of 9 months of age. The subjects (Ss) lived 3-4 in acrylic cages with water and food pellets ad libitum, under a 12:12 light-dark cycle (lights on at 0700), whit-controlled temperature and humidity in the recording room. All Ss were implanted to record EEG, EMG and EOG to characterize immobility episodes (IE′s) in a control 8 h recording and after i.c.v. administration of [Ala 11, D-Leu 15]-orexin B with 1, 3 and 10 nmol/1 μL. We measured the number, mean duration and latency to the first IE′s. Results The administration of [Ala 11, D-Leu 15]-orexin B significantly reduced the number of IE′s (P<0.01), from 4.28 ± 1.5 IE′s to just 0.25 ± 0.17 with 10 nmol/1 μL dose, but did not change the amount of awakening, slow wave or rapid eye movement sleep. Importantly, the number or orexins neurons were similar between taiep and Sprague-Dawley rats. Conclusion The myelin mutant taiep rats is a model of narcolepsy with cataplexy with normal number of orexin neurons in the lateral hypothalamus. Additionally, a specific orexin B agonist reduced IE′s without any effect the sleep pattern. This could be useful for the design of new treatments. Support CONACYT grants 243333 and 243247 to CC and JRE, respectively. Grants from VIEP-BUAP 2019 and CA in Neuroendocrinología BUAP-CA-288.