Summary:
ABSTRACT
In this thesis we are aiming to understand the neuroprotective role of Nurr1, a
transcription factor that is related to Parkinson disease. We used hemizygous
for Nurr1 mice (Nurr1+/-), since the homozygote deletion of Νurr1 is lethal,
and Knock out (nhr-6) worms. We examined these organisms via behavioral and
pharmacological tests using two compounds (BRF-001 in mice and XCT in C.
elegans), which have been shown to be neuroprotective in vitro. We investigated
whether there is dopaminergic sensitivity in Nurr+/- mice using the following
behavioral tests: the pole test, the beam traversal test, and the rearing test.
The results did not demonstrate any significant differences between Nurr1+/-
and wild type mice. Despite the above, we showed that Nurr+/- hets are
hyperactive compared with wild type mice pre- and post- amphetamine injection.
Moreover, we examined the effect of BRF-001 administration in wild type mice,
but we did not observe any significant differences between treated and
untreated animals. On the other hand, we also examined the function of the
orthologous nhr6 gene in C. elegans. Nhr6 is responsible for the formation of
the spermatheca (reproductive organ ) in C. elegans. However, we investigated
the mobility of Knock out (nhr6-) compared with wild type worms and we showed
that the Knock out animals are hypoactive and have motion alterations. At the
same time, we examined the effect of XCT in C.elegans’ fecundity. We
demonstrated that XCT affects the fecundity of wild type mice and apparently
affects protein complexes that include the nhr6. As a conclusion, our data
indicated that increase of Nurr1 function via compounds that activate NURR1/RXR
heterodimers have the capacity to be neuroprotective.
Keywords:
Parkinson, Behavioral tests, Nurr1/nhr6, Mice, locomotor activity