MICROGLIAL AND ASTROCYTIC INVOLVEMENT IN A MURINE MODEL OF PARKINSONS-DISEASE INDUCED BY 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE (MPTP)

We have studied the reaction of glial cells in mice treated with an in traperitoneal administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropy ridine (MPTP), a selective neurotoxin of dopaminergic nigrostriatal ne urons. Signs of injury to the dopaminergic neurons started on the Ist day after MPTP administration and progressed up to the end of the obse rvation time (21st day). A transient microglial reaction was demonstra ted from the Ist until the 14th day in the substantia nigra (SN) and s triatum. The cells showed an increase in number and changes in morphol ogy. At the ultrastructural level, signs of phagocytosis and features indicating the secretion of biologically active substances were observ ed. Astrocytosis followed the microglial reaction by one day and was n oticed until the end of the observation time. Interleukin-6 immunoreac tivity was observed within microglia and astrocytes in the SN on days 2 and 3. There were no signs of depletion of dopaminergic cells or gli al activation after the administration of MPTP simultaneously with par gyline, an inhibitor of monoamine oxidase-B that prevents MPTP neuroto xicity. Our study indicates that microglia and astrocytes are involved in the pathological process in the nigrostriatal system following MPT P administration. MPTP alone is not responsible for glial cell activat ion but its metabolite MPP+ and/or agents released by injured neurons may participate in this process. (C) 1998 Elsevier Science B.V. All ri ghts reserved.