TITLE:
A mutation in protein kinase C-gamma alters SNC neuron morphology and decreases synaptic vesicles in dopaminergic striatal terminals in the AS/AGU rat
AUTHORS:
Abdullah Glil Al-Kushi, David Russell, Anthony Philip Payne
KEYWORDS:
PKC-Gamma; Nigral DA Neurons and Terminals; PKC-Gamma; SNC Neurons; Dopaminergic Terminals
JOURNAL NAME:
Journal of Biomedical Science and Engineering,
Vol.6 No.12,
December
20,
2013
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.