caa a22 4500 445377240 CHVBK 20180317143006.0 cr unu---uuuuu 170323e20110801xx s 000 0 eng 10.1007/s00702-010-0568-3 doi (NATIONALLICENCE)springer-10.1007/s00702-010-0568-3 Mice with genetic deletion of the heparin-binding growth factor midkine exhibit early preclinical features of Parkinson's disease [Elektronische Daten] [Rui Prediger, Argelia Rojas-Mayorquin, Aderbal Aguiar Jr, Caroline Chevarin, Raymond Mongeau, Michel Hamon, Laurence Lanfumey, Elaine Del Bel, Hisako Muramatsu, José Courty, Rita Raisman-Vozari] There is considerable evidence showing that the neurodegenerative processes that lead to sporadic Parkinson's disease (PD) begin many years before the appearance of the characteristic motor symptoms and that impairments in olfactory, cognitive and motor functions are associated with time-dependent disruption of dopaminergic neurotransmission in different brain areas. Midkine is a 13-kDa retinoic acid-induced heparin-binding growth factor involved in many biological processes in the central nervous system such as cell migration, neurogenesis and tissue repair. The abnormal midkine expression may be associated with neurochemical dysfunction in the dopaminergic system and cognitive impairments in rodents. Here, we employed adult midkine knockout mice (Mdk−/−) to further investigate the relevance of midkine in dopaminergic neurotransmission and in olfactory, cognitive and motor functions. Mdk/− mice displayed pronounced impairments in their olfactory discrimination ability and short-term social recognition memory with no gross motor alterations. Moreover, the genetic deletion of midkine decreased the expression of the enzyme tyrosine hydroxylase in the substantia nigra reducing partially the levels of dopamine and its metabolites in the olfactory bulb and striatum of mice. These findings indicate that the genetic deletion of midkine causes a partial loss of dopaminergic neurons and depletion of dopamine, resulting in olfactory and memory deficits with no major motor impairments. Therefore, Mdk−/− mice may represent a promising animal model for the study of the early stages of PD and for testing new therapeutic strategies to restore sensorial and cognitive processes in PD. Springer-Verlag, 2011 Parkinson ' s disease nationallicence Midkine nationallicence Olfactory discrimination nationallicence Learning and memory nationallicence Motor nationallicence Animal model nationallicence Knockout mice nationallicence Prediger Rui Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, UFSC, Campus Trindade, 88049-900, Florianópolis, SC, Brazil aut Rojas-Mayorquin Argelia UMR-S 975, INSERM, UPMC, CRICM, Experimental Therapeutics of Neurodegeneration, 75013, Paris, France aut Aguiar Jr Aderbal Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, UFSC, Campus Trindade, 88049-900, Florianópolis, SC, Brazil aut Chevarin Caroline INSERM UMR S677, 75013, Paris, France aut Mongeau Raymond INSERM UMR S677, 75013, Paris, France aut Hamon Michel INSERM UMR S677, 75013, Paris, France aut Lanfumey Laurence INSERM UMR S677, 75013, Paris, France aut Del Bel Elaine Departamento MEF-Fisiologia, Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo, USP, Ribeirão Prêto, SP, Brazil aut Muramatsu Hisako Faculty of Psychological and Physical Sciences, Aichi Gakuin University, 470-0195, Nisshin, Aichi, Japan aut Courty José Laboratoire de Recherche sur la Croissance Cellulaire, la Réparation et la Régénération Tissulaires (CRRET), CNRS UMR 7149, Université Paris XII, Créteil Cedex, France aut Raisman-Vozari Rita UMR-S 975, INSERM, UPMC, CRICM, Experimental Therapeutics of Neurodegeneration, 75013, Paris, France aut Journal of Neural Transmission Springer Vienna 118/8(2011-08-01), 1215-1225 0300-9564 118:8<1215 2011 118 702 https://doi.org/10.1007/s00702-010-0568-3 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00702-010-0568-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Prediger Rui Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, UFSC, Campus Trindade, 88049-900, Florianópolis, SC, Brazil aut NATIONALLICENCE 700 1- Rojas-Mayorquin Argelia UMR-S 975, INSERM, UPMC, CRICM, Experimental Therapeutics of Neurodegeneration, 75013, Paris, France aut NATIONALLICENCE 700 1- Aguiar Jr Aderbal Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, UFSC, Campus Trindade, 88049-900, Florianópolis, SC, Brazil aut NATIONALLICENCE 700 1- Chevarin Caroline INSERM UMR S677, 75013, Paris, France aut NATIONALLICENCE 700 1- Mongeau Raymond INSERM UMR S677, 75013, Paris, France aut NATIONALLICENCE 700 1- Hamon Michel INSERM UMR S677, 75013, Paris, France aut NATIONALLICENCE 700 1- Lanfumey Laurence INSERM UMR S677, 75013, Paris, France aut NATIONALLICENCE 700 1- Del Bel Elaine Departamento MEF-Fisiologia, Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo, USP, Ribeirão Prêto, SP, Brazil aut NATIONALLICENCE 700 1- Muramatsu Hisako Faculty of Psychological and Physical Sciences, Aichi Gakuin University, 470-0195, Nisshin, Aichi, Japan aut NATIONALLICENCE 700 1- Courty José Laboratoire de Recherche sur la Croissance Cellulaire, la Réparation et la Régénération Tissulaires (CRRET), CNRS UMR 7149, Université Paris XII, Créteil Cedex, France aut NATIONALLICENCE 700 1- Raisman-Vozari Rita UMR-S 975, INSERM, UPMC, CRICM, Experimental Therapeutics of Neurodegeneration, 75013, Paris, France aut NATIONALLICENCE 773 0- Journal of Neural Transmission Springer Vienna 118/8(2011-08-01), 1215-1225 0300-9564 118:8<1215 2011 118 702 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer