title: Upregulation and axonal transport of synaptotagmin-IV in the direct-pathway medium spiny neurons in hemi-parkinsonian rats induced by dopamine D1 receptor stimulation.
abstract: Synaptotagmin-IV (Syt-IV) may function as a regulator of Ca(2+) -dependent synaptic transmission. In the hemi-parkinsonian rats with unilateral lesions of dopaminergic nigrostriatal neurons Syt-IV and substance-P (SP) mRNAs could be upregulated within the dopaminergically hypersensitive striatum of the lesioned brain hemisphere via the stimulation of striatal dopamine D1 (D1-R), but not D2 receptors. The hypersensitive D1-R-mediated transmission may be the culprit for the undesired expression of levodopa-induced dyskinesia, implying the involvement of Syt-IV and SP in the process. First, striatal cellular phenotypes expressing Syt-IV were determined. It was found to be expressed in all striatal neurons and a small population of astrocytes. Then it was examined, if the D1-R-mediated upregulation of Syt-IV mRNA may result in the upregulation of the translated protein. It was found that, after acute stimulation with a selective D1 agonist, (±)-6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide (SKF-82958), Syt-IV was elevated within the SP-expressing striatal neurons of the lesioned side. This was followed by the upregulation of Syt-IV, but not of its mRNA, within the ipsilateral target nuclei of the direct-pathway medium spiny neurons, indicating axonal transport of de novo synthesized protein to their SP-positive synaptic terminals. However, despite the striatal upregulation of SP and Syt-IV following a similar time-course, their subcellular co-localization within the axonal terminals was not found. It was therefore suggested that Syt-IV may regulate the hypersensitive striatal synaptic transmission, although via a SP-independent mechanism.
authors.affiliation: Brain Research Laboratory, Medical Faculty, Institute of Pathophysiology, University of Ljubljana, Zaloška 4, 1000, Ljubljana, Slovenia.
authors.forename: Larisa
authors.initials: L
authors.lastname: Tratnjek
authors.affiliation: Department of Biology, Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Gordana
authors.initials: G
authors.lastname: Glavan
authors.affiliation: Institute of Cell Biology, Medical Faculty, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Tanja
authors.initials: T
authors.lastname: Višnjar
authors.affiliation: Brain Research Laboratory, Medical Faculty, Institute of Pathophysiology, University of Ljubljana, Zaloška 4, 1000, Ljubljana, Slovenia.
authors.forename: Marko
authors.initials: M
authors.lastname: Živin
mesh_terms: D000818:Animals; D001370:Axonal Transport; D001552:Benzazepines / Q000494:pharmacology; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D018491:Dopamine Agonists / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000378:metabolism* / Q000502:physiology; D008297:Male; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000209:etiology / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000378:metabolism*; D050857:Synaptotagmins / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D001552:Benzazepines; D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; D050857:Synaptotagmins; C071262:SK&F 82958; D016627:Oxidopamine
keywords: D1 stimulation; dopaminergic hypersensitivity; substance-P