Hypocretin (orexin) cell transplantation as a new therapeutic approach in narcolepsy

Abstract

Narcolepsy is a neurodegenerative disorder which main includes symptoms such as daytime sleepiness, sleep paralysis, hypnagogic hallucinations, disturbed nocturnal sleep as well as cataplexy. It is known that this disease is caused by deficiency of the neurotransmission system of the peptide named hypocretin (HCRT), also cited as orexin (OX). The ablation of HCRT/OX or HCRT/OX receptors in animal models has supported the understanding of the human narcolepsy. The current chapter describe the experimental model of narcolepsy in rats by pharmacological means. Targeting HCRT/OX neurons by the HCRT-2-saporin (HCRT2/SAP) toxin destroys the HCRT neurons. This experimental procedure promotes a significant diminution in number of HCRT/OX neurons as well as the endogenous levels of the peptide in the cerebrospinal fluid. We also discuss that HCRT2/SAP induces narcoleptic-like behaviour in rats as assessed by EEG/EMG means. Under this paradigm, here we present current evidence regarding the potential use of grafting HCRT neurons into lateral hypothalamus of lesioned rats to revert the sleep abnormalities observed in HCRT2/SAP animals.