Mice given Ex-4 (20 nM, 0.25 μL/h in the lateral ventricle over 7 days) were protected from MPTP-induced damage of the dopaminergic system, quantitatively assessed by TH immunohistochemical analysis of the SN and TH immunoblot analyses of the striatum at 7 days. (A) Representative SN sections from control, and MPTP-treated mice with and without Ex-4. (B) Compared with controls, TH(+) cells in SN were reduced by MPTP (*P < .05). Those from mice given Ex-4 and MPTP were no different from controls (P > .05). (C) Similarly, as assessed by immunoblotting in striatum, TH levels were significantly reduced by MPTP (*P < .05 vs. controls) and no different from controls for mice given Ex-4 and MPTP (P > .05, Dunnett's t-test, n = 10/group). (D) Mice given Ex-4 were protected from MPTP-induced depletion of brain DA and metabolites (DOPAC and HVA). DA, DOPAC, and HVA from striatum were quantified by HPLC at 7 days in mice treated with PBS, MPTP, and MPTP plus Ex-4. Levels of each were reduced by MPTP (P < .05 vs. PBS) and preserved by Ex-4 (P > .05 vs. PBS; P < .05 vs. MPTP) compared with controls (Dunnett's t-test, n = 10). The ratios of DOPAC:DA and HVA:DA were 0.08 and 0.065 in controls, 0.16 and 0.31 in MPTP-treated mice, and 0.095 and 0.08 in MPTP plus Ex-4–treated mice.