5 research outputs found
Chondroitin sulfates restrict axonal growth along the projection path of vestibular nuclear (VN) neurons across the hindbrain of prenatal rats
Poster PresentationIn our study of chondroitin sulfate proteoglycan (CSPG)
deposition in rhombomere boundaries of the developing
hindbrain, we found chondroitin 6-sulfotransferase (C6ST)-
expressing cells within rhombomeres of E8.5 to E10.5
mouse embryos. This is coincident with the growth of axons
from vestibular nuclear (VN) neurons across the hindbrain.
The spatio-temporal concurrence of axonal growth and CS-expressing cells in the hindbrain suggests a role of CSPGs
in determining the axonal trajectory of VN neurons. To perturb
the possible effect of hindbrain CS in axonal development
from the VN neurons, chondroitinase ABC (ChABC)
was injected into the fourth ventricle of Sprague–Dawley rats
at E12.5, comparable to E9.5 in mouse. The embryos were
maintained in vitro for 24 h. Axons from the VN neurons
were then traced with DiI labeling. Successful removal of
CS chains was confirmed when the fixed embryos were immunostained
for CSPG stubs revealed by the enzyme. Controls
were injected instead with PBS vehicle. Results showed
that with the control injection, the axons of the VN neurons
advanced towards the midline and barely crossed the midline
to the contralateral side of the neurotube. In embryos injected
with ChABC, the axons were defasciculated when compared
with the PBS-treated embryos, even though there was no significant
change in the normal trajectories of the axons. These
results suggested that the CS components were important in
confining the axonal path of the VN neurons as they crossed
the midline. Further examination of the axonal projection pattern
of VN neurons as perturbed by ChABC treatment in earlier
stages of embryos is in progress to determine the period in
which CS moieties contribute to the restriction of growing
axons to their projection path.
Acknowledgement: Supported by HK RGC grant HKU
7294/01M.link_to_subscribed_fulltextThe 23rd Scientific Meeting of the Hong Kong Society of Neurosciences. Hong Kong, 2004. In Neuroscience Letters, 2004, v. 370 n. supplement, p. S13-S1
Selective knockdown of gene expression of N-methyl-D-aspartate receptor one ameliorates parkinsonian motor symptom in 6-hydroxydopamine-lesioned rats
The present study reported the efficacy of antisense oligonucleotides specific for N-methyl-D-aspartate receptor one (NR1) in reduction of motor symptom in a rat parkinsonian model, the unilateral 6-hydroxydopamine-lesioned rat. Significant reductions in apomorphine-induced contralateral rotation were only seen in the NR1 antisense-treated lesioned rats (after a single intraparenchymal dose of antisense to the lesioned neostriatum; 15nmol in 3μl of saline) at 1 or 2 days after the treatment. No motor effect was seen in the lesioned animals with control treatments (sham, treatment using NR1 sense oligonucleotides, randomized oligonucleotides or saline, respectively). In contrast, significant increases in expression of NR1 mRNA in the lesioned neostriatum were seen in rats with control treatments but not in rats with NR1 antisense treatment. Importantly, in the lesioned neostriatum that was treated with NR1 antisense, a significant reduction in NR1 protein expression was found and NR1 immunoreactivity was seen to reduce in perikarya of presumed striatal medium spiny neurons. The present data indicate that a single dose of NR1 antisense ameliorates motor symptom in the rat model. The efficacy of NR1 antisense is likely to be mediated by a selective knockdown in expression of NR1 mRNA and proteins in the presumed medium spiny neurons. © 2003 Elsevier Ltd. All rights reserved.link_to_subscribed_fulltex