Abstract
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.
Highlights
IntroductionThere has been increased interest in the links between neurodegenerative conditions, protein kinases and kinase signaling pathways [1,2] including the protein kinase C (PKC) family [3]
There has been increased interest in the links between neurodegenerative conditions, protein kinases and kinase signaling pathways [1,2] including the protein kinase C (PKC) family [3].The AS/AGU rat is an Albino Swiss-derived mutant which carries a recessive mutation in the gene coding for the gamma isoform of protein kinase C [4]
All rats were killed with carbon dioxide euthanasia and perfused via the left ventricle with mammalian Ringer solution [200 ml] containing the vasodilator Lignocaine followed by 500 ml 3% glutaraldehyde [Agar-Aldrich Inc, P6148] in 0.1 M phosphate buffer (PB), blood and excess fluid being drained via an incision through the right atrium
Summary
There has been increased interest in the links between neurodegenerative conditions, protein kinases and kinase signaling pathways [1,2] including the protein kinase C (PKC) family [3]. The AS/AGU rat is an Albino Swiss-derived mutant which carries a recessive mutation (agu) in the gene coding for the gamma isoform of protein kinase C [4]. The rats are characterized by movement impairments including rigidity of the hind limbs, a staggering gait, a tendency to fall over every few step, a slight whole body tremor and difficulty in initiating movements [5,6] and by progressive dysfunction of the nigro-striatal dopaminergic [DA] and raphe-striatal serotonergic (5-HT) systems. The chief defect in both systems is a failure to release transmitter within the striatum under normal physiological conditions. There are no cellular inclusions such as Lewy bodies, though some molecules associated with Lewy bodies, such as ubiquitin and parkin, are elevated [10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
