دانلود رایگان مقاله اختلال نقص در یادگیری هیجانی در موش ناک اوت neurotrimin

ABSTRACT

Neurotrimin (Ntm) belongs to the IgLON family of cell adhesion molecules with Lsamp, Obcam and kilon that regulate the outgrowth of neurites mostly by forming heterodimers. IgLONs have been associated with psychiatric disorders, intelligence, body weight, heart disease and tumours. This study provides an initial behavioural and pharmacological characterization of the phenotype of Ntm-deficient mice. We expected to see at least some overlap with the phenotype of Lsamp-deficient mice as Ntm and Lsamp are the main interaction partners in the IgLON family and are colocalized in some brain regions. However, Ntm-deficient mice displayed none of the deviations in behaviour that we have previously shown in Lsamp-deficient mice, but differently from Lsamp-deficient mice, had a deficit in emotional learning in the active avoidance task. The only overlap was decreased sensitivity to the locomotor stimulating effect of amphetamine in both knockout models. Thus, despite being interaction partners, on the behavioural level Lsamp seems to play a much more central role than Ntm and the roles of these two proteins seem to be complementary rather than overlapping.

4. Discussion

This study gives an initial characterization of the phenotype of Ntm deficient mice. We found these mice to have normal body weight, no gross vision, hearing or olfaction deficiencies and no alterations in pain sensitivity. Ntm and Lsamp are colocalized in a few brain regions and act as heterophilic dimers, so we expected to find at least some overlap in the phenotypes of Lsamp−/− and Ntm−/− mice as in colocalization regions the deletion of either partner should result in the lack of functional heterodimers. However, Ntm−/− mice had much less differences compared to wild-type mice than Lsamp−/− mice in studies by Innos et al. [10–12]. Unlike Lsamp−/− mice, Ntm−/− mice had no differences in anxiety, social interaction and locomotor activity, displayed normal exploratory activity, barbering behaviour and swimming speed, and showed no altered sensitivity to the sedative effect of ethanol. As for overlapping changes in phenotype, similarly to Lsamp−/− mice, Ntm−/− mice had lower sensitivity to the loco motor stimulating effect of amphetamine, but the magnitude of this difference was much smaller than in Lsamp−/− animals. The results of the three learning experiments indicate that invalidation of the Ntm gene may result in inferior performance only in cognitively challenging emotional learning tasks (active avoidance), but not in simple emotional learning tasks (fear conditioning) or learning paradigms involving mainly hippocampus (spatial navigation in the Morris water maze). Learning deficiency revealed in active avoidance is indirectly in line with studies associating Ntm with cognitive function and intelligence [16,24]. Table 2 gives a comparison ofthe behavioural phenotypes of Ntm−/− and Lsamp−/−mice, underlining the difference of these two knockout mouse models on the behavioural level.