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Publication : Increase in presynaptic territory of C-terminals on lumbar motoneurons of G93A SOD1 mice during disease progression.

First Author  Pullen AH Year  2009
Journal  Eur J Neurosci Volume  29
Issue  3 Pages  551-61
PubMed ID  19187267 Mgi Jnum  J:146652
Mgi Id  MGI:3838090 Doi  10.1111/j.1460-9568.2008.06602.x
Citation  Pullen AH, et al. (2009) Increase in presynaptic territory of C-terminals on lumbar motoneurons of G93A SOD1 mice during disease progression. Eur J Neurosci 29(3):551-61
abstractText  Compensatory synaptic plasticity is reported in muscle and the central nervous system of motor neuron disease patients, and transgenic SOD1 mice, but direct ultrastructural evidence for spinal motoneurons is lacking. Prompted by our observation in spinal cords from autopsied patients suggesting selective enlargement of the ultrastructurally distinctive C-type terminal synapsing with spinal motoneurons, we examined the ultrastructural synaptology of lumbar motoneurons during disease progression in age- and sex-matched wild-type mice, transgenic G93A SOD1 mice, and mice overexpressing normal human SOD1 (Wt(SOD1)). Prescribed criteria classified presynaptic terminals of motoneurons into five ultrastructural classes (S, F, T, M, and C). Computerized morphometry on electronmicrographs was used to measure their appositional lengths, coverage of the motoneuron membrane, and sizes of postsynaptic structures. No terminal degeneration occurred in wild-type or Wt(SOD1) mice. In transgenic mice, degeneration of motoneurons and S-terminals and F-terminals commenced presymptomatically (10 weeks), and continued into the symptomatic stage (18 weeks). However, C-terminals were preserved. Morphometry confirmed significant reductions in frequency and membrane coverage for S-terminals and F-terminals between 10 and 18 weeks, but a maintained frequency of C-terminals coupled with increased appositional length and coverage of the motoneuron membrane. Increased C-terminal size was matched by growth of its characterizing postsynaptic cistern and Nissl body. The results reveal selective preservation and increased presynaptic territory of the C-type terminal. As C-terminals derive from cholinergic intrasegmental propriospinal interneurons and may modulate motoneuron excitability, their increased presynaptic territory on surviving motoneurons of transgenic SOD1 mice may represent a means of maintaining excitability, compensating for the loss of overall presynaptic input.
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