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Tyrosine hydroxylase and Lewy body molecules immunoreactivity in the SNC neurons of an AS/AGU mutantrat

World Journal of Neuroscience 2012年第3期2卷 150-155页

作者： A. G. Al-Kushi D. Russell A. P. Payne College of Medicine Umm Alqura University Makkah KSA School of Life Sciences Glasgow University Glasgow UK

The AS/AGU rat has a recessive single point mutation in the gene coding for the gamma isoform of protein kinase C (pkc-γ) resulting in a failure to release dopamine in the striatum and impaired movement including a staggering gait, difficulty in initiating movement and a slight whole body tremor. This study examined the levels tyrosine hydroxylase, ubiquitin and parkin in individual SNC cell bodies, there was no evidence of a reduction in tyrosine hydroxylase levels although levels of ubiquitin and parkin were elevated in the cytoplasm. The findings support the hypothesis that the initial bar to dopamine availability in the striatum is reduced release, with substantia nigra cell death being a later phenomenon.

关键词： pkc-gamma Tyrosine Hydroxylase Ubiquitin Parkin

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A mutation in protein kinase C-gamma alters SNC neuron morphology and decreases synaptic vesicles in dopaminergic striatal terminals in the AS/AGU rat

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Journal of Biomedical Science and Engineering 2013年第12期6卷 1129-1136页

作者： Abdullah Glil Al-Kushi David Russell Anthony Philip Payne College of Medicine Umm Alqura University Makkah Kingdom of Saudi Arabia School of Life Sciences Glasgow University UK

A spontaneous mutation in the Albino Swiss (AS) rat has been shown to be a single point mutation (agu) in the gene coding for the gamma isoform of protein kinase C (pkc-γ). The characteristics of the mutant include movement disorders, a failure to release dopamine in the striatum and elevations of molecules such as parkin and ubiquitin in the substantia nigra pars compacta (SNC). This present study examined SNC cell bodies and dopaminergic synaptic terminals within the caudate-putamen. Cell volume and nuclear volume were reduced in the AS/AGU mutant compared to the AS control, but the volume fractions of mitochondria and rough endoplasmic reticulum were significantly higher. No Lewy bodies were present in the mutant, although microglia were found adjacent to some SNC cells. Dopaminergic terminals were identified in the caudate-putamen by electron microscopy with low-glutaraldehyde fixation and immunohistochemistry for tyrosine hydroxylase using immuno-gold visualisation. AS/AGU mutant rats had less than half of the synaptic vesicles of AS controls;this was not only true of “readily-releasable” zones adjacent to the synaptic cleft but also “storage pool” zones. The findings support the hypothesis that the initial bar to dopamine availability in the striatum is the reduced release, with nigral cell death being a later phenomenon.

关键词： pkc-gamma Nigral DA Neurons and Terminals SNC Neurons Dopaminergic Terminals

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