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Interleukin-6 (IL-6) in addition to its role in the immune system has the potential to modulate several brain functions including learning and memory processes. In the present study we investigated the role of IL-6 in CNS function in male mice not expressing IL-6 (C57BL/6J IL6-/-tm 1 Kopf) and wild type mice (WT) used as controls. The animals were kept in standard conditions with water and food available ad libitum except during experiments. All testing took place between 8.30 AM and 12.30 PM. Each group consisted of 13 animals. In order to evaluate a role of endogenous IL-6 in cognitive functions “object recognition test” for the evaluation of recognition memory was used. In an attempt to evaluate whether observed effect was memory specifi c, the level of anxiety and psychomotor activity of mice was evaluated in an “elevated plus maze” test and in an open fi eld, respectively. Recognition memory, measured by the difference in exploration of the new object and a duplicate of the familiar one, presented 1 h earlier, was impaired in IL-6 defi cient mice. Moreover, lack of IL-6 signifi cantly attenuated locomotor and exploratory activity measured in an open fi eld test and enhanced anxiety evaluated in an “elevated plus maze” test. Results of this study indicate that IL-6 defi ciency impairs recognition memory, attenuates locomotor and exploratory activity and enhances anxiety in mice. The study was supported by the Polish Ministry of Science grant Nr 2P05B01826.
HTLV-1 infection is linked with a neurodegenerative disorder HTLV1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). Expression of the singly or doubly spliced ORF-I cDNA of HTLV-1 results in the production of the 12 kD and 8 kD protein isoforms. The uncleaved 12 kD form resides in the ER and affects MHC-I and IL-2R. The cleaved 8 kD form traffi cs to the cell surface, is recruited to the immunological synapse upon T-Cell Receptor (TCR) stimulation decreasing TCR signaling and viral replication. Genetic analysis of ORF-I from ex vivo samples of HTLV-1 infected individuals reveals amino acid substitutions that affect its proteolytic cleavage, suggesting that ER or membrane associated functions of ORF-I may contribute to the persistence of HTLV-1 infected T-cells in the host. To investigate a putative relationship between ORF-I forms and provirus level, the best predictor of disease development, we measured the provirus level in the blood and linked it with the presence of ORF-I isoforms. The provirus levels ranged from 0.2 to 165 copies of proviral DNA per 106 PBMCs. DNA sequencing and reverse genetics revealed mutations at/in the vicinity of both cleavage sites within ORF-I. A rare mutation found at position 26 in ORF-I resulted mainly in the presence of the 8 kD isoform. Importantly, patients with this mutation had signifi cantly lower virus that those that carried either 12 kD isoform or both forms, and with one exception they belonged to a healthy carrier group.
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