Morphological and functional characteristics of LPS-stimulated microglial cells under the action of orexin A

Abstract

Interest to the orexin-containing neurons is caused by their recent discovery and perspectives of their usage for treatment of different diseases. The studies in this area were launched recently and are of special interest since the opportunity of modulating functional activity of the brain immune system is of pivotal significance for therapy of various central nervous system (CNS) disorders providing novel ways of search and promising data on therapeutic effects of orexins in inflammatory, autoimmune diseases as well as malignant tumors.
 Some data from literature show that orexins may exert therapeutic effects in different disorders caused by altered neuroimmune interactions. Participation of this neuromediator system is shown in pathogenesis of narcolepsia, obesity, multiple sclerosis, Alzheimer disease, intestinal disorders, septic shock and cancer, due to involvement of orexins in functional regulation of various components of immune syste, e.g., microglial cell populations. Despite only scarce data on these effects, some experimental results obtained over last years, add to our understanding of orexin effects upon functional activity of the brain immune system.
 A number of previous studies allowed to assess the orexin effects on morpho-functional features of microglial cells activated by lipopolysaccharide (LPS), thus presenting a prospective for development of novel approaches to therapy of infectious, inflammatory, neurodegenerative and autoimmune disorders affecting CNS. In the present study, we aimed for detecting the effects of neuromediator orexin A upon functional traits of of microglial cells activated by LPS (M1 phenotype) as evaluated by changes of their size and length of their processes, as well as density of cell distribution.
 We have studied the changes of microglia cell numbers following intraperitoneal LPS injection. It was shown that, the LPS causes higher activation degree of these cells, i.e., the contents of microglial cells becomes increased in somatosensory area of the brain cortex. A series of these studies allowed us to demonstrate that intracerebroventricular injection of orexin A in animals following LPS injection does not cause detectable changes of the processes initiated by LPS. The comparative analysis did not detect any changes in length of microglial processes localized in somatosensory or motor cortical areas, and corpus striatum. Other parameters of the microglial cell activation will be studied in future.