Pleiotrophin prevents cocaine-induced toxicity in vitro

Pleiotrophin over-expression provides trophic support to dopaminergic neurons in parkinsonian rats

“…Importantly, PTN trophic effects on cultured dopaminergic neurons appear not to be mediated by products released by glial cells, but seem to result from a direct action of PTN on dopaminergic neurons [9]. Finally, antibodies against PTN reduce the viability of cultured PC12 cells, a prototypical catecholaminergic cell line, suggesting that PC12 cells support themselves through PTN release [24]. More studies are needed to determine if adult dopaminergic neurons depend on trophic support through an autocrine/paracrine pathway involving PTN in vivo .…”

Pleiotrophin overexpression regulates amphetamine-induced reward and striatal dopaminergic denervation without changing the expression of dopamine D1 and D2 receptors: Implications for neuroinflammation

“…PTN (3 μM) limits amphetamine-and cocaine-induced decrease in PC12 and NG108-15 cell viability (Gramage et al, 2008;Gramage et al, 2010a;2010b). However, our results show that the net effect produced by PTN seems to differ in vivo, suggesting overall deleterious effects triggered by activation of PTN downstream pathways that could counteract its trophic actions on neurons.…”

Mechanisms of Action and Persistent Neuroplasticity by Drugs of Abuse

“…In cultured fetal mesencephalic DA neurons, a 5-day cocaine treatment (10 25 and 10 24 M) produced no effect on levels of TH-positive cells or high-affinity [ 3 H]DA uptake (Bennett et al, 1993). However, other studies employing PC12 cells found that cocaine treatment produced DNA fragmentation, cytotoxicity, decreases in Bcl-2, and increases in caspase-3 levels (Gramage et al, 2008;Lepsch et al, 2009). Furthermore, the cocaine metabolite benzoylecgonine has been reported to be cytotoxic (Lin and Leskawa, 1994).…”