Pleiotrophin exhibits a trophic effect on survival of dopaminergic neurons in vitro

다국어 초록 (Multilingual Abstract)

To understand what kind of trophic factors are up-regulated in dopamine(DA)-depleted striatum, we first analysed the up-regulation of mRNAs using a DNA microarray in DA-depleted striatum where DAergic inputs were denervated by 6-OHDA. We then investigated whether or not such trophic factors had an effect on cultured dopaminergic neurons. The microarray analysis revealed that pleiotrophin (PTN), glial-derived neurotopic factor(GDNF) and others were up-regulated in DA-depleted striatum. As PTN has been reported to have a wide range of trophic effects on neurons, we focused on the functional role of PTN in the present study. The increase in PTN mRNA was confirmed by Northern blotting at 1-3 weeks after the lesion, reaching a peak at 1 week. In embryonic day 15 mesencephalic neuron culture, PTN increased the number of tyrosine hydroxylase (TH)-positive neurons in a dose-dependent manner (125.2±2.0% of the control at 50ng/mL), while a family protein, midkine(10ng/mL) did not show any trophic effect (99.3±0.7%). In addition, the PTN effect on DAergic neurons was additive to the GDNF effect. As PTN did not increase the number of microtubule-associated protein-2(MAP 2)-positive neurons or promote the proliferation of dopaminergic progenitors in a bromodeoxyuridine(BrdU) labelling study, the effect appeared to enhance the specific survival of dopaminergic neurons. Expression of PTN receptors (syndecan-3, PTP-ζ) was detected on the cultured mesencephalic neurons, and also up-regulated in DA-depleted striatum. The data indicate that PTN is up-regulated in DA-depleted striatum and exhibits a trophic effect specifically on the survival of cultured dopaminergic neurons.