A stable and easily reproducible model of focal white matter demyelination.
J Neurosci Methods
; 307: 230-239, 2018 09 01.
Article
in En
| MEDLINE
| ID: mdl-29859880
ABSTRACT
BACKGROUND:
Demyelination is the end product of numerous pathological processes, and also is one of the main causes of neurological disability in Multiple sclerosis (MS). Research into the pathogenesis of MS is hampered by the conventional rodent models' inability to produce stable demyelination. NEWMETHOD:
Focal demyelinating lesions were stereotactically targeted to the corpus callosum with a two-point injection of lysophosphatidylcholine (LPC-2) in mice. Three groups were analyzed (nâ¯=â¯8, each) and water maze, sensorimotor test, and compound action potential were included in functional tests. Electron microscopy was used for morphological analyses while western blot and immunohistochemistry were included for molecular detection.RESULTS:
Ten days after the LPC-2 injection, the expression of myelin basic protein (MBP) was reduced, while non-phosphorylated neurofilament (SMI-32) was increased. The amplitude of the N1 segment decreased and less well-defined myelin sheaths was found. Behavioral tests showed increased latency to escape and reduced time spent in target quadrant. Four weeks later, MBP expression still reduced, SMI-32 expression was increased, both spatial learning (D24-D27) and spatial memory (D28) were still significantly impaired in LPC-2 injection mice. COMPARISON WITH EXISTING METHOD(S) Compared with the classic single-point LPC-injection model, our studies showed that the two-point LPC-injection not only could induce demyelination in a short-term manner, but also could cause demyelination in a long-term manner with little remyelination in the mouse corpus callosum.CONCLUSIONS:
We established a simple, reliable, and inexpensive model of demyelination in the corpus callosum in mice, with functional and morphological reproducibility, and good validity.Key words
Full text:
1
Database:
MEDLINE
Main subject:
Demyelinating Autoimmune Diseases, CNS
/
Disease Models, Animal
/
Leukoencephalopathies
Limits:
Animals
Language:
En
Year:
2018
Type:
Article