Research ReportVisual evoked potentials and MBP gene expression imply endogenous myelin repair in adult rat optic nerve and chiasm following local lysolecithin induced demyelination
Research highlights
►Lysolecithin injection into the optic chiasm causes alterations in VEP records. ►VEP records confirmed endogenous myelin repair. Changes in ►VEP records are correlated with the expression of myelin basic protein. ►VEP records provide useful evaluating tool for the efficacy of myelin repair strategies.
Introduction
Axonal myelination in vertebrate central nervous system is fundamental for conductance of electrical pulses, whereas, demyelination can develop serious diseases such as multiple sclerosis (MS) (Noseworthy et al., 2000). MS is the most common demyelinating disease among young adults with mean age of onset about 30 years (Shivane and Chakrabarty, 2007). This disease commonly affects the optic pathway, particularly optic nerves and chiasm in more than 70% of patients (Guazzo, 2005). Optic nerve and chiasm neuritis is one of the first clinical signs that have been reported in patients suffering from MS (Beck et al., 1983, Feinstein, 1999). Demyelination may be followed by an incomplete spontaneous remyelination (Scolding et al., 1998, Scolding, 2001). Actually, it is reported that some CNS lesions of multiple sclerosis in humans are remyelinated by oligodendrocytes (Prineas and Connell, 1979, Rodriguez and Sheithauer, 1994) or Schwann cells (Ghatak et al., 1973), although most parts of lesions show extensive demyelination and gliosis without myelin repair (Pavelko et al., 1998).
MS as an autoimmune, inflammatory, demyelinating and neurodegenerative disease needs numerous investigations on its multi-aspect nature by different approaches (Zamvil and Steinman, 2003). The endogenous mechanisms responsible for triggering the disease development have not yet been entirely determined. Matute and colleagues proposed that oligodendroglial damage as a result of the toxic substances may be a primary and/or secondary etiological component of MS (Matute et al., 2001). Lysolecithin (LPC) is an analog of lysophosphatidilcholine and has detergent effect with a particular influence on myelinating cells (Low et al., 1983, Allt et al., 1988, Dousset et al., 1995). In comparison with other toxins such as ethidium bromide, LPC with more effect on myelinating cells has generally the slightest toxicity to other cells like astrocytes and can then provide demyelination and subsequent repair in a shorter period of time (Woodruff and Franklin, 1999a). Therefore, it can be an appropriate toxin for producing local and acute demyelination in CNS.
A common symptom observed in MS is altered sensory perception. It is reported that there are blurred vision or scotoma, and almost all of them are produced by involvements of both optic nerves and chiasm in patients (Prineas et al., 2002). Study of latencies and amplitudes of VEPs elicited by light stimuli has proven to be a very useful means of MS clinical evaluation, since it can reveal the presence of demyelination and remyelination anywhere in the optic paths (Halliday, 1993, Brusa et al., 1999).
Myelin basic proteins (MBPs) are a family of positively charged proteins that contribute to formation and compaction of myelin sheath (Baumann and Pham-Dine, 2001). During myelination, these proteins are expressed in a highly coordinated sequence (Woodruff and Franklin, 1999b). Expression of mRNA for myelin basic protein is coordinately reduced during the demyelinating phase and then up-regulated during the remyelinating phase (Toews et al., 1990).
In the present study, we report functional alterations in the visual pathway caused by direct injection of LPC into the optic nerves and chiasm by monitoring VEPs. We have also measured changes in the expression of MBP as a molecular index of demyelination and remyelination.
Section snippets
Electrophysiological evaluation of lysolecithin-induced demyelination
Stereotaxic atlas of rat brain showed the level of bregma (bregma: 0 μm) in equal with bi-fractioning site of optic nerves from chiasm in coronal sections. Dye distribution studies proved a confined injection into chiasm without extra distribution within surrounding cerebrospinal fluid or other brain structures (data not shown). Acquired results from myelin staining of serial sections (data not shown) demonstrated that LPC was able to diffuse in an area with length of 800–1500 μm. It was also
Discussion
The optic pathway of the rat provides an excellent model for combined structural, functional and biochemical studies of gliogenesis and myelinogenesis (Skof et al., 1976, Uzman, 1964). The optic nerve is free of neuronal cell bodies, and glial cell types can be readily identified (Uzman, 1964), thus permitting studies on proliferation and differentiation of oligodendroglia (Skof et al., 1976). Here, we have studied the LPC-induced demyelination and remyelination processes using VEPs recording.
Acknowledgments
This research was supported by grants from Tarbiat Modares University and Iran National Sciences Foundation (grant #87020491).
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S. M. and M.A. S. have made same contribution in this report.