Affiliations: Department of General Pathology and Pathophysiology, Institute of Experimental Medicine of the Northwest Branch of the Russian Academy of Medical Sciences, Saint Petersburg, Russia | Department of Neuroimmunology, Max-Plank-Institute of Neurobiology, Munich, Germany and Institute of Clinical Neuroimmunology, Ludwig-Maximilians University Munich, Munich, Germany | Department of Neuroimmunology, Max-Plank-Institute of Neurobiology, Munich, Germany | Department of General Pathology and Pathophysiology, Institute of Experimental Medicine of the Northwest Branch of the Russian Academy of Medical Sciences, Saint Petersburg, Russia
Note:  Correspondence to: Sofia V. Perekrest, 194376 Acad. Pavlov str., 12. St. Petersburg, Russia. Tel.: +7 812 2340764/+7 921 5841013; Fax: +7 812 2349493; E-mail: [email protected] Authors contributed equally to this study.
Note:  Authors contributed equally to this study.
Abstract: Background/Aim: There is growing interest in the possible role of orexin in pathophysiological processes of multiple sclerosis (MS) for these patients frequently complain of fatigue and sleep disturbances and orexin is a neuropeptide known to play the crucial role in sleep/wakefulness regulation as well as in many other physiological functions. The present study was aimed to investigate morpho-functional characteristics of hypothalamic orexin system during adoptive transfer experimental autoimmune encephalomyelitis (atEAE). Method: Immunohistochemical detection of orexin-containing neurons was carried out on frontal brain sections of intact and atEAE Lewis rats. Quantity and relative transmission density (RTD) of orexin-positive neurons were assessed in definite hypothalamic structures on different brain levels (Swanson's atlas). Preproorexin gene expression in hypothalamic cells was assessed by qPCR. Results: Though the total quantity of orexin-positive cells was decreased in atEAE animals, differential quantification of these neurons revealed discreteness of hypothalamic zones response. Three possible variants can be distinguished: reduction of orexin-positive neurons quantity without any changes in their RTD (DMHa, LHAd, LHAvm); increase of RTD with no alterations in the quantity (more medial hypothalamic structures); both quantity reduction and RTD increment (more lateral hypothalamic structures). The preproorexin gene expression in hypothalamic cells of atEAE animals was slightly increased, that evidence the possible raise of orexin synthesis. Conclusion: atEAE induction causes alterations in balance between processes of orexin synthesis and utilization with the predomination of the latter. Hypothalamic orexinergic system participates in central mechanisms of CNS response to atEAE induction that could be important for understanding the pathogenetic processes during multiple sclerosis.