| First Author | Gramage E | Year | 2010 |
| Journal | Neuroscience | Volume | 170 |
| Issue | 1 | Pages | 308-16 |
| PubMed ID | 20620199 | Mgi Jnum | J:165207 |
| Mgi Id | MGI:4836444 | Doi | 10.1016/j.neuroscience.2010.06.078 |
| Citation | Gramage E, et al. (2010) Genetic inactivation of pleiotrophin triggers amphetamine-induced cell loss in the substantia nigra and enhances amphetamine neurotoxicity in the striatum. Neuroscience 170(1):308-16 |
| abstractText | Pleiotrophin (PTN) is a neurotrophic factor with important effects in survival and differentiation of dopaminergic neurons that has been suggested to play important roles in drug of abuse-induced neurotoxicity. To test this hypothesis, we have studied the effects of amphetamine (10 mg/kg, four times, every 2 h) on the nigrostriatal pathway of PTN genetically deficient (PTN-/-) mice. We found that amphetamine causes a significantly enhanced loss of dopaminergic terminals in the striatum of PTN-/- mice compared to wild type (WT+/+) mice. In addition, we found a significant decrease ( approximately 20%) of tyrosine hydroxylase (TH)-positive neurons only in the substantia nigra of amphetamine-treated PTN-/- mice, whereas this area of WT+/+ animals remained unaffected after amphetamine treatment. This effect was accompanied by enhanced amphetamine-induced astrocytosis in the substantia nigra of PTN-/- mice. Interestingly, we found a significant decrease in the phosphorylation levels of p42 extracellular-signal regulated kinase (ERK2) in both saline- and amphetamine-treated PTN-/- mice, whereas phosphorylation of p44 ERK (ERK1) was almost abolished in the striatum of PTN-/- mice compared to WT+/+ mice, suggesting that basal deficiencies in the phosphorylation levels of ERK1/2 could underlie the higher vulnerability of PTN-/- mice to amphetamine-induced neurotoxic effects. The data suggest an important role of PTN in the protection of nigrostriatal pathways against amphetamine insult. |
