Phenotypic Plasticity of Grafted Catecholaminergic Neurons and its Regulatory Mechanisms.

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1. Using model rats of hemi-parkinson's disease, the mechanisms of functional recovery after grafting of dopaminergic cells were investigated. We found : 1) the survival of TH mRNA/TH positive cells, 2) increase of dopamine synthesis/release, 3) synaptic connections, 4) recovery of dopamine transporter and 5) normalization of D_1 and D_2 receptor-bindings.2. Bovine total ganglioside (tGS), sialosyl cholesterol (ganglioside analogue), IL-6 (B cell stimulating cytokine) facilitated the development/growth of grafted dopaminergic cells, and promoted the motor recovery.3.1) grafted chromaffin (adrenergic) cells transmute to dopaminergic neurons in dopamine-depleted striatum, 2) grafted noradrenergic cells transmute to dopaminergic cells in dopa-mine-depleted striatum but not in the lateral ventricle, 3) dopaminergic neurons grow much better in dopamine-depleted striatum than in normal striatum or the cortex, 4) grafted cholinergic neurons grow in a similar fashion in normal and dopamine-depleted striatum, 5) co-cultured midbrain neurons (partly dopaminergic neurons) extend more neurites faster toward the dopamine-depleted than toward the intact striatal tissue. These evidences suggest the increase in synthesis/release of some trophic factors for dopaminergic neurons in dopamine-depleted striatum.4. In soluble fraction of dopamine-depleted striatal tissue a few acidic proteins increased. The purification/identification of these proteins is under way.