Genetic inactivation of Pleiotrophin triggers amphetamine-induced cell loss in the substantia nigra and enhances amphetamine neurotoxicity in the striatum

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.…”

“…In previous studies, it was shown that PTN-/-mice exhibit exacerbated amphetamine-induced dopaminergic damage in the nigrostriatal pathway (Gramage et al, 2010a;2010b). Thus, we hypothesized a possible neuroprotective role of PTN in response to the neurotoxic effects of amphetamine.…”

“…As previously performed (Gramage et al, 2010b), cell counts were made in standardized areas (325 x 435 µm) obtaining the mean from three sections per animal. Striatal TH-positive fiber staining was assessed by optical density (OD) measurements using Image-Pro Plus software (Version 3.0.1; Media Cybernetics, Silver Spring, MD).…”

“…The compartment with white walls was the non-preferred compartment in a similar manner by both genotypes (30 -40% stay of total time in the preconditioning phase). This `biased` apparatus and subject assignment, in which mice are paired with the drug in the non-preferred compartment, was previously used to study genotypic differences in amphetamine-and cocaine-induced CPP (Gramage et al, 2013b;Gramage et al, 2010b).…”

“…Furthermore, a periadolescent amphetamine treatment was found to produce transient cognitive deficits only in PTN-/-mice, not in wild type (WT) mice (Gramage et al, 2013a). Interestingly, amphetamine-induced neurotoxic effects in the nigrostriatal pathway are enhanced in PTN-/-mice compared to WT mice (Gramage et al, 2010b;Soto-Montenegro et al, 2015). Also, it has to be noted that amphetamine-induced increase of GFAP-positive astrocytes, a hallmark of the neuroinflammation induced by this type of psychostimulants, was slightly increased in the striatum of PTN-/-mice (Gramage et al, 2010a).…”