Effects of hypocretin/orexin cell transplantation on narcoleptic-like sleep behavior in rats.

Abstract

The sleep disorder narcolepsy is now considered a neurodegenerative disease because there is a massive loss of neurons containing the neuropeptide hypocretin/orexin (HCRT). In consequence, narcoleptic patients have very low cerebrospinal fluid (CSF) levels of HCRT. Studies in animal models of narcolepsy have shown the neurophysiological role of the HCRT system in the development of this disease. For example, the injection of the neurotoxin named hypocretin-2-saporin (HCRT2/SAP) into the lateral hypothalamus (LH) destroys the HCRT neurons, therefore diminishes the contents of HCRT in the CSF and induces narcoleptic-like behavior in rats. Transplants of various cell types have been used to induce recovery in a variety of neurodegenerative animal models. In models such as Parkinson's disease, cell survival has been shown to be small but satisfactory. Similarly, cell transplantation could be employed to implant grafts of HCRT cells into the LH or even other brain regions to treat narcolepsy. Here, we report for the first time that transplantation of HCRT neurons into the LH of HCRT2/SAP-lesioned rats diminishes narcoleptic-like sleep behavior. Therefore, cell transplantation may provide an effective method to treat narcolepsy.