A possitive effect of progesterone on corticostriatal glutamatergic pathway of hemiparkinsonims rats model.

CASAS S.; CREMASCHI F.; NANFARO F.; YUNES R.; CABRERA R.

Londres

Congreso; X Word Congress of International Neuromodulation Society (INMS); 2011

INMS

Parkinson?s disease (PD) is the second most common neurodegenerative disorder. It affects about 1% of the population over 55 years, with a mean age of onset of 60 years. Pharmacological treatments relieve symptoms, but none of them halt or retard dopaminergic neuron degeneration. Progesterone (P) neuroprotection has been reported in experimental brain damage as well as peripheral nerve and spinal cord injuries. We test the effects of progesterone on corticostriatal glutamatergic pathway in an adult rat model of PD generated via a unilateral intrastriatal injection of the neurotoxin 6-hydroxydopamine (6-OHDA). Animals were randomly selected in order to be intrastriataly injected with 6-OHDA or receive instead a saline injection. After seven days the rats were randomly assigned to one of 4 experimental groups: 1) sham group: they were neither lesioned with 6-OHDA nor administered any experimental treatment at all; 2) progesterone control group: same as in group 1, but the subjects in this group were administered progesterone 4 mg/kg s.c. at noon for three consecutive days; 3)hemiparkinsonian group: same as in group 1, but the subjects were lesioned by administration of 6-OHDA in their left striatum during surgery, without any further treatment; and 4) hemiparkinsonian/progesterone group: same as in group 3, but the subjects were administered progesterone 4 mg/kg s.c. at noon for three consecutive days. Eight weeks post-lesion the animals were decapitated and the striatum was dissected out. The glutamatergic activity was measured by the release of [3H]glutamate from the left and right striatum. For the statistical analysis we utilized a Student t test. Data were expressed as the mean ± S.E.M. Differences between means with a p < .05 were considered significant. We observed a significant difference between left (L) and right (R) striatum [3H]glutamatergic activity in the hemiparkinsonian group (L=71.67±7.83;R=46±3.05). On the other hand, no change was observed in the sham group (L=33.33±5.23;R=34.67±5.69) and the hemiparkinsonian/progesterone group (L=36.33±8.19;R=22±2.64). We proposed that possibly neuroactive steroids like P? among others? could have a potential neuroprotective effect regarding different neurotoxins, mediated by modulatory changes on nigrostriatal dopaminergic system.