An NR2B-Dependent Decrease in the Expression of trkB Receptors Precedes the Disappearance of Dopaminergic Cells in Substantia Nigra in a Rat Model of Presymptomatic Parkinson's Disease
Ifenprodil, an antagonist of NR2B containing NMDA receptors, prevents the decrease in trkB-IR and TH-IR cells occurring in SNc 14 days after 6-OHDA intrastriatal injection. Positive cells for trkB and TH immunostaining in SNc were counted in coronal midbrain slices of treated rats as described in Section 2. Four groups of rats in each case (a) and (b) were pretreated with saline solution or Ifenprodil (5 mg/kg, i.p.), 1 day before and 3, 5, and 7 days after unilateral 6-OHDA (black columns) or ascorbic acid (sham, white columns) intrastriatal administration. The IHC studies were performed 14 days after 6-OHDA or ascorbic acid injections. Results were expressed as a percentage of trkB-IR cells (a) or TH-IR cells (b) in the ipsilateral SNc compared with the contralateral side. (a) Number of cells with trkB-IR signals in sample areas per slice from contralateral SNc was equal to , , , and cells/mm2 in sham-saline, 6-OHDA-saline, sham-Ifenprodil, and 6-OHDA-Ifenprodil rats, respectively. (b) Number of TH-IR cells in sample areas per slice from contralateral SNc was equal to , , , and cells/mm2 in sham-saline, 6-OHDA-saline, sham-Ifenprodil, and 6-OHDA-Ifenprodil rats, respectively. The different experimental groups were compared by a Kruskal-Wallis nonparametric ANOVA, followed by a -test. *, when comparing saline-6-OHDA versus saline-sham rats. # when comparing saline-6-OHDA versus Ifenprodil-6OHDA rats. rats under each experimental condition.