Neuroprotection of estradiol in a Parkinson?s disease model in female rats: effect on motor dysfunctions, BDNF expression and striatal dopamine release

GIULIANI FERNANDO; HERRERA MACARENA; VALENTIN JURI THIERRY; CAMPO VERDE ARBOCCO, FIORELLA; CABRERA RICARDO

Ciudad de Mendoza

Workshop; International Workshop in Neuroendocrinology (IWNE 2015); 2015

International Neuroendocrine Federation- Universidad de Mendoza

Parkinson?s disease (PD) is the second most common neurodegenerative disorder, with a prevalence that is higher in men regarding women. This has raised the hypothesis that female hormones could have neuroprotective properties. Their actions might be evidenced as improvements in the motor symptoms as well as changes in the expression of neurotrophic factors or in the neuronal activity of the affected brain areas. OBJECTIVES: To determine in an experimental model of the neuropathology (hemiparkinsonian rats) if estradiol (E) treatment could: 1) improve the motor dysfunctions; 2) induce changes in the striatal mRNA expression of BDNF; and 3) modify the striatal dopamine release. METHODS: We used ovariectomized adult rats that were unilaterally injected in right corpus striatum with either the neurotoxic 6-hydroxydopamine (HP rats), or vehicle (sham rats) as controls. Five days after lesion they were treated with a subcutaneous daily treatment of either 0.1μg/kg estradiol (HP-E group) or vehicle (HP-group and sham-group) for 10 consecutive days. To assess the objective 1, eight weeks after lesion we assayed for each rat stepping, curling and apomorphine-induced turning behavior tests. After that, we killed them by decapitation and dissected out the corpus striata. A subset of each tissue was assigned to mRNA extraction and ulterior RTqPCR of BDNF (objective 2). The other subset was separated to superfusion assays with [3H]-dopamine to study the ex vivo K+-evoked release of this neurotransmitter (objective 3). All data were compared by 1-way ANOVA (p<0.05 considered as statistically significant). RESULTS: 1) The contralateral turning behavior (turns towards the left) was increased in rats of the HP group regarding sham group (p<0.01). This effect was reverted in the HP-E group (p<0.05). In turn, there was a reduction in the number of steps and an increase in the deviation of the corporal axis in rats of the HP group regarding sham group (p<0.01 in both, stepping and curling behavior tests). These effects were reverted in HP-E group (p<0.01 in both tests). 2) There was a reduction in the mRNA expression of BDNF in the right striata of rats belonging to the HP group regarding sham group (p<0.01). The treatment with E induced an increase in the mRNA expression of this factor (p<0.05). 3) The K+-evoked dopamine release was decreased in the right striata of HP rats regarding sham rats (p<0.05). This effect was reverted in HP-E rats (p<0.05). CONCLUSIONS: our results suggest that estradiol could be an important neuroprotective molecule against neurodegeneration. Its effect on BDNF expression and dopamine release could explain in part the improvement in the motor symptoms that we observed in this animal model of PD.