MPP+ injection into rat substantia nigra causes secondary glial activationbut not cell death in the ipsilateral striatum

Injection of MPP+ into the substantia nigra causes extensive necrosis and a nterograde degeneration of pars compacta dopaminergic neurons. We studied s econdary effects in the ipsilateral striatum by examining dopaminergic term inals, signs of neuronal damage, and glial reactivity at 1, 2, 3, and 7 day s after injection of MPP+ into the substantia nigra. Dopaminergic terminals and uptake sites were evaluated with [H-3]GBR-12935 binding and tyrosine h ydroxylase immunoreactivity. Glial reaction was examined with markers of as trocytes and microglia. Stereology was used to evaluate any changes in neur onal density. Tyrosine hydroxylase immunoreactivity and [H-3]GBR-12935 bind ing markedly decreased (74%) from days 2 to 7. Loss of dopaminergic termina ls in the ipsilateral striatum was accompanied by an intense astroglial and , to a lesser extent, microglial reaction. However, no signs of cell damage , neuronal loss, or disruption of the blood-brain barrier were found in the striatum. Resident astroglial and microglial cells showed a morphological shift and notable changes in protein expression typical of glial reactivity , yet the presence of macrophage-like cells was not detected. This study sh ows that injection of MPP+ in the substantia nigra causes a secondary react ion within the ipsilateral striatum involving the transformation of quiesce nt glia to reactive glia. It is suggested that stimuli derived from damaged dopaminergic terminals within the striatum are able to activate resident g lia and that this glial transformation may promote repair and regeneration. (C) 2000 Academic Press.