title: Neurochemical and behavioral characteristics of toxic milk mice: an animal model of Wilson's disease.
abstract: Toxic milk mice have an inherited defect of copper metabolism. Hepatic phenotype of the toxic milk mice is similar to clinical findings in humans suffering from Wilson's disease (WND). In the present study, neurotransmitter system and locomotor performance in toxic milk mice was examined to verify the feasibility of this animal model for studying neuropathology of WND. Mice aged 2 and 12 months were used in the experiment. The mice were tested according to rotarod and footprint protocols. Monoamine content in brain structures was measured by high performance liquid chromatography. In order to detect neuronal loss, expression of enzymes specific for dopaminergic [tyrosine hydroxylase (TH)], noradrenergic (dopamine beta-hydroxylase) and serotoninergic [tryptophan hydroxylase (TPH)] neurons was analyzed by Western blot. The 12-month-old toxic milk mice demonstrated impaired locomotor performance in behavioral tests. Motor deficits were accompanied by increased copper and serotonin content in different brain regions and slight decrease in dopamine concentration in the striatum. The expression of TH, dopamine beta-hydroxylase and TPH in the various brain structures did not differ between toxic milk mice and control animals. Despite differences in brain pathology between humans and rodents, further exploration of neuronal injury in toxic milk mice is warranted to broaden the understanding of neuropathology in WND.
authors.affiliation: Department of Clinical and Experimental Pharmacology, Medical University of Warsaw, ul. Krakowskie Przedmiescie 26/28, 00-927, Warsaw, Poland, aprzybylkowski@wum.edu.pl.
authors.forename: Adam
authors.initials: A
authors.lastname: Przybyłkowski
authors.forename: Grażyna
authors.initials: G
authors.lastname: Gromadzka
authors.forename: Adriana
authors.initials: A
authors.lastname: Wawer
authors.forename: Ewa
authors.initials: E
authors.lastname: Bulska
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Jabłonka-Salach
authors.forename: Tomasz
authors.initials: T
authors.lastname: Grygorowicz
authors.forename: Anna
authors.initials: A
authors.lastname: Schnejder-Pachołek
authors.forename: Andrzej
authors.initials: A
authors.lastname: Członkowski
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D000818:Animals; D001923:Brain Chemistry; D027682:Cation Transport Proteins / Q000235:genetics; D000073840:Copper-Transporting ATPases; D004195:Disease Models, Animal; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D005260:Female; D006527:Hepatolenticular Degeneration / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008892:Milk / Q000633:toxicity*; D009043:Motor Activity / Q000502:physiology; D045442:Rotarod Performance Test; D014365:Tryptophan Hydroxylase / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: C486201:Atp7a protein, mouse; D027682:Cation Transport Proteins; D014446:Tyrosine 3-Monooxygenase; D014365:Tryptophan Hydroxylase; D004299:Dopamine beta-Hydroxylase; D000251:Adenosine Triphosphatases; D000073840:Copper-Transporting ATPases