Abstract
Trimethyltin (TMT) is an organotin compound which is considered a useful tool to obtain an animal model of neurodegeneration associated with cognitive impairment (Pompili et al., 2011; Geloso et al., 2011). In the present work, this model was used in order to investigate the animal behaviour in association with the immunohistochemical expression of dopaminergic system (D1- and D2-like receptors and dopamine transporters DAT, VMAT-1 and -2) and cells viability (NEU-N) in the rat hippocampus and facial nucleus regions. TMT-treated group showed impaired spatial reference memory in a Morris water maze task compared to control group whereas the memory consolidation tested 24h after was preserved. In the open field, TMT-treated rats showed a decreased in time spent in rearing episodes reflecting a lower interest to explore a novel environment. In the hippocampal area of TMT-treated group, cell viability was significantly reduced by 45.9% whereas the D1, D2, DAT and VMAT- 2 receptor proteins immunoreactivity was significantly decreased by 57.5, 72.8, 64.1, 72.1%. In the facial nucleus, immunoreactivity reduction was observed only for dopamine transporters (average: 60% about) while the NEU-N reduction was 40%. These data were confirmed by real time RT-PCR analysis. These results suggest a differential involvement of the D1-type and D2-type receptors in the regulation of learning and memory. Besides, alterations on the functional ratio of DAT to VMAT-2 could predispose the cells to injury even at very low doses of TMT. The data obtained in facial nucleus demonstrate a different sensibility to xenobiotic of dopamine receptors and transporters. The TMT model could contribute to elucidate the role of dopaminergic system on two different CNS regions. Supported by PRIN 2008 - prot. 20089MANHH_002 and prot. 20089MANHH_003.
