Support to an association of the striatal synaptotagmin 7 mRNA up-regulation with dopaminergic hypersensitivity
Robert Pal¹, Marko Živin¹, Aleksandra Milutinovič², Branimir Jernej³, Gordana Glavan¹
¹Brain Research Laboratory, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Slovenia;
²Institute of Histology and Embriology, Faculty of Medicine, University of Ljubljana, Slovenia;
³Laboratory of Neurochemistry and Molecular Neurobiology, Rudjer Bošković Institute, Zagreb, Croatia
Synaptotagmin 7 (Syt 7) is a Ca2+ sensor implicated in the regulation of membrane fusion in vesicular transport. Dopaminergic drugs have been shown to up-regulate its expression in the hypersensitive striatum of 6-hydroxydopamine-treated rats (Glavan and Živin 2005, Neuroscience 135:545-554). In this study we investigate whether dopamine receptor agonist-up-regulation of Syt 7 mRNA is specifically involved in the pathophysiological adaptations of hypersensitive striatum by analyzing other dopaminergic neurons containing brain regions. We treated rats with systemic reserpine injections that rapidly depletes dopamine throughout the brain, but leaves dopaminergic neurons spared from destruction. We analyzed the effects of apomorphine, a D1 and D2 receptor agonist on Syt 7 mRNA expression in caudate putamen, nucleus accumbens, cingulate cortex, substantia nigra compacta, ventral tegmental area and hippocampus using in situ hybridization. The treatment with reserpine resulted in akinesia, catalepsy, rigidity and down-regulation of preprotachykinin (PPT) mRNA in caudate putamen, indicating a severe depletion. We confirmed the development of striatal hypersensitivity by the apomorphine-induced up-regulation of PPT mRNA. Apomorphine increased Syt 7 mRNA levels only in the striatum (caudate putamen and nucleus accumbens) of reserpinized rats, having no effect in other brain regions. We conclude that after reserpine treatment in the dopamine depleted striatum the up-regulation of Syt 7 could play a specific role as part of hypersensitive response to dopaminergic agonists.
Keywords: synaptotagmin VII, dopaminergic hypersensitivity, reserpine, preprotachykinin, in situ hybridization