Multiple sclerosis (MS) is a progressive T cell-mediated autoimmune demyelinating inflammatory disease of the central nervous system (CNS). Although it is recognized that cognitive deficits represent a manifestation of the disease, the underlying pathogenic mechanisms remain unknown. Here we provide evidence of spatial reference memory impairments during the pre-motor phase of experimental autoimmune encephalomyelitis (EAE) in mice. Specifically, these cognitive deficits were accompanied by down-regulation of choline acetyltransferase (ChAT) mRNA expression on day 5 and 11 post-immunization, and up-regulation of inflammatory cytokines in the hippocampus and prefrontal cortex. Moreover, a marked increase in B1R mRNA expression occurred selectively in the hippocampus, whereas protein level was up-regulated in both brain areas. Genetic deletion of kinin B1R attenuated cognitive deficits and cholinergic dysfunction, and blocked mRNA expression of both IL-17 and IFN-γ in the prefrontal cortex, lymph node and spleen of mice subjected to EAE. The discovery of kinin receptors, mainly B1R, as a target for controlling neuroinflammatory response, as well as the cognitive deficits induced by EAE may foster the therapeutic exploitation of the kallikrein-kinin system (KKS), in particular for the treatment of autoimmune disorders, such as MS, mainly during pre-symptomatic phase. © 2013 Elsevier Inc.
R.C., D., E.L.G., M., T.B., A., R., M., R.D., P., & J.B., C. (2013). Spatial reference memory deficits precede motor dysfunction in an experimental autoimmune encephalomyelitis model: The role of kallikrein-kinin system. Brain, Behavior, and Immunity, 33, 90–101. https://doi.org/10.1016/j.bbi.2013.06.002 LK - http://sfx-44gp-h.hosted.exlibrisgroup.com/44gp_h?sid=EMBASE&issn=08891591&id=doi:10.1016%2Fj.bbi.2013.06.002&atitle=Spatial+reference+memory+deficits+precede+motor+dysfunction+in+an+experimental+autoimmune+encephalomyelitis+model%3A+The+role+of+kallikrein-kinin+system&stitle=Brain+Behav.+Immun.&title=Brain%2C+Behavior%2C+and+Immunity&volume=33&issue=&spage=90&epage=101&aulast=Dutra&aufirst=Rafael+C.&auinit=R.C.&aufull=Dutra+R.C.&coden=BBIME&isbn=&pages=90-101&dat