Cognitive dysfunction is relatively frequent in multiple sclerosis (MS) and it happens from the early stages of the disease. There is increasing evidence that the grey matter may be involved in autoimmune inflammation during relapses of MS. The purpose of this study was to evaluate if a single transfer of encephalitogenic T cells, mimicking a relapse of MS, may cause hippocampal damage and memory disturbances in rats. Lewis rats were injected with anti-MBP CD4+ T cells, that induced one-phase autoimmune encephalomyelitis (EAE) with full recovery from motor impairments at 10-15 days. The spatial learning and memory were tested by the Morris water maze test in control and EAE animals, 30 and 90 days post-induction (dpi). The neural injury and inflammation was investigated in the hippocampus by immunohistochemistry and quantitative analyses. There was a marked decrease in the number of CA1 and CA4 pyramidal neurons 5 dpi. The loss of neurons then aggravated till the 90 dpi. An increase in microglial and astroglial activation and in pro-inflammatory cytokines mRNA expression in the hippocampus, were present 30 and 90 dpi. Nerve growth factor and brain-derived neurotrophic factor mRNA levels were also significantly elevated. The water maze test, however, did not reveal memory deficits. The present data indicate that a single transfer of autoimmune T cells results in preserved inflammation and probable on-going neuronal injury in the hippocampus, long after recovery from motor disturbances. These findings suggest that any relapse of the MS may start the neurodegenerative process in the hippocampus, which is not necessarily connected with memory deficits.
Keywords: BDNF; DIR; DNF; EAE; GAPDH; GFAP; IL; Iba1; MLV; MOG; MRI; Moloney murine leukaemia virus; NGF; NeuN; PBS; TNF; autoimmune encephalomyelitis; brain-derived neurotrophic factor; days post EAE induction; double inversion recovery; dpi; glial fibrillary acidic protein; glyceraldehyde 3-phosphate dehydrogenase; hippocampus; interleukin; ionized calcium-binding adaptor molecule 1; magnetic resonance imaging; memory; multiple sclerosis; myelin oligodendrocyte glycoprotein; nerve growth factor; neurodegeneration; neuroinflammation; nuclear neuron protein; phosphate-buffered saline; tumour necrosis factor.
Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.