Pink1-deficiency in mice impairs gait, olfaction and serotonergic innervation of the olfactory bulb
| Autor: | Ralf Kühn, Ulrich Hafen, Martin Hrabé de Angelis, Andreas Hofmann, Karina Kloos, Daniela M. Vogt Weisenhorn, Julia Zerle, Lisa Glasl, Sabine M. Hölter, Konstanze F. Winklhofer, Florian Giesert, Anne Roethig, Jingzhong Zhang, Wolfgang Wurst, Barbara Di Benedetto |
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| Rok vydání: | 2011 |
| Předmět: |
Adrenergic Neurons
physiology [Gait] PINK1 Cell Count Olfaction Mitochondrion Biology Motor Activity Serotonergic Mice Developmental Neuroscience metabolism [Serotonergic Neurons] medicine Animals ddc:610 metabolism [Protein Kinases] Gait metabolism [Olfactory Bulb] Kinase metabolism [Corpus Striatum] Dopaminergic Neurons metabolism [Dopaminergic Neurons] genetics [Protein Kinases] Neurodegeneration Dopaminergic physiology [Smell] metabolism [Mitochondria] medicine.disease Olfactory Bulb Corpus Striatum metabolism [Adrenergic Neurons] Olfactory bulb Mitochondria Smell Disease Models Animal physiology [Motor Activity] Neurology PTEN-induced putative kinase Neuroscience Protein Kinases Serotonergic Neurons |
| Zdroj: | Experimental neurology 235(1), 214-227 (2012). doi:10.1016/j.expneurol.2012.01.002 |
| ISSN: | 1090-2430 |
| DOI: | 10.1016/j.expneurol.2012.01.002 |
| Popis: | Parkinson's Disease (PD) is the most common neurodegenerative movement disorder. Autosomal-recessive mutations in the mitochondrial protein kinase PINK1 (PTEN-induced kinase 1) account for 1-2% of the hereditary early-onset cases. To study the mechanisms underlying disease development, we generated Pink1-deficient mice. In analogy to other genetic loss-of-function mouse models, Pink1(-/-) mice did not show morphological alterations in the dopaminergic system. As a consequence, no gross motor dysfunctions were observed indicating that these mice do not develop the cardinal symptoms of PD. Nonetheless, symptoms which develop mainly before bradykinesia, rigidity and resting tremor were clearly evident in Pink1-deficient mice. These symptoms were gait alterations and olfactory dysfunctions. Remarkably in the glomerular layer of the olfactory bulb the density of serotonergic fibers was significantly reduced. Concerning mitochondrial morphology, neurons in Pink1(-/-) mice had less fragmented mitochondria. In contrast, upon acute knock-down of Pink1 increased mitochondrial fragmentation was observed in neuronal cultures. This fragmentation was, however, evened out within days. Taken together, we demonstrate that Pink1-deficient mice exhibit behavioral symptoms of early phases of PD and present systematic experimental evidence for compensation of Pink1-deficiency at the cellular level. Thus, Pink1-deficient mice represent a model for the early phases of PD in which compensation may still impede the onset of neurodegeneration. Consequently, these mice are a valuable tool for studying Pink1-related PD development, as well as for searching for reliable PD biomarkers. |
| Databáze: | OpenAIRE |
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