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Non‐motor behavioural impairments in parkin‐deficient mice
Author(s) -
Zhu XinRan,
Maskri Lyutha,
Herold Christina,
Bader Verian,
Stichel Christine C.,
Güntürkün Onur,
Lübbert Hermann
Publication year - 2007
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2007.05812.x
Subject(s) - parkin , dopaminergic , dopamine , endocrinology , mptp , striatum , rotarod performance test , homovanillic acid , medicine , tyrosine hydroxylase , 3,4 dihydroxyphenylacetic acid , parkinson's disease , psychology , neuroscience , morris water navigation task , biology , hippocampus , serotonin , disease , motor activity , receptor
Mutations in the parkin gene are the major cause of early‐onset familial Parkinson's disease (PD). We previously reported the generation and analysis of a knockout mouse carrying a deletion of exon 3 in the parkin gene. F1 hybrid pa +/– mice were backcrossed to wild‐type C57Bl/6 for three more generations to establish a pa –/–(F4) mouse line. The appearance of tyrosine hydroxylase‐positive neurons was normal in young and aged pa –/– (F4) animals. Loss of parkin function in mice did not enhance vulnerability of dopaminergic neurons to 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) toxicity. However, the pa –/– (F4) mice displayed impaired exploration and habituation to a new environment and exhibited thigmotaxis behaviour in the open field and Morris water maze. Abnormal anxiety‐related behaviour of pa –/– (F4) mice was also observed in the light/dark exploration test paradigm. Dopamine metabolism was enhanced in the striatum of pa –/– (F4) mice, as revealed by increased homovanillic acid (HVA) content and a reduced ratio of dihydroxyphenylacetic acid (DOPAC)/HVA. The alterations found in the dopaminergic system could be responsible for the behavioural impairments of pa –/– (F4) mice. Consistent with a recent observation of cognitive dysfunction in parkin‐linked patients with PD, our findings provide evidence of a physiological role of parkin in non‐motor behaviour, possibly representing a disease stage that precedes dopaminergic neuron loss.