FIG 8.

SGK1 overexpression protected MPTP-induced dopaminergic neuronal cell death in the substantia nigra in C57BL/6J mice by inhibiting MKK4-mediated JNK activation. (A) TH immunohistochemistry for a representative saline-treated mouse, an MPTP-treated mouse, and an MPTP-treated mouse in which AdV-SGK1 was overexpressed for 21 days prior to MPTP treatment. A total of 1 × 10¹⁰ viral particles of AdV-SGK1 were injected into the striatum 21 days prior to an acute treatment regimen of 18 mg/kg MPTP (1 dose every 2 h for 4 doses). (B) Stereological quantification of TH-positive neurons in different treatment groups (i) and the measured volume of midbrain section used for the TH neuron analysis (ii). ISI, ipsilateral; IP, intraperitoneal. *, P < 0.01 between either saline plus saline or AdV-SGK1 plus saline and saline plus MPTP; **, P < 0.01 between saline plus MPTP and Adv-SGK1 plus MPTP. (C) Western immunoblot analysis of phospho-SGK1, phospho-MKK4 (Ser257/Thr261), phosphor-MKK4 (Ser78), phospho-JNK, and phospho-c-Jun in midbrains treated with saline, saline/MPTP, and MPTP/AdV-SGK1 was performed (i). Expression of these proteins was quantitated and normalized to that of α-tubulin for the respective treatments (ii).