Elsevier

Brain Research

Volume 1351, 10 September 2010, Pages 50-56
Brain Research

Research Report
Visual evoked potentials and MBP gene expression imply endogenous myelin repair in adult rat optic nerve and chiasm following local lysolecithin induced demyelination

https://doi.org/10.1016/j.brainres.2010.07.026Get rights and content

Abstract

Multiple sclerosis (MS) patients may suffer from optic disturbances. Toxin-induced demyelinations have frequently been developed to investigate the cellular and structural aspects of demyelination and remyelination processes, separately. The present study describes functional consequence of lysolecithin (LPC)-induced lesion in the adult rat optic nerves and chiasm by recording the visual evoked potentials (VEPs) from the visual cortex and its correlation with myelin basic protein (MBP) expression in lesion site. Records of VEP were obtained at 2, 7, 14 and 28 days post-injection. We observed that the VEPs generated by light stimuli progressively changed in both amplitude and latency after the lesion as well as in comparison with those generated in control animals. These observations were confirmed through measurement of mRNA expression level for MBP which is one of the important genes expressed in mature oligodendrocytes and Schwann cells. The level of MBP mRNAs in demyelinated chiasm and optic nerves decreased following lysolecithin injection with its least value on day 7, and then it increased to the control level 14 days post-lesion. However, it continued to increase even after that and reached a maximum level 28 days post lesion. Results of the present paper show that, LPC injection in the chiasm share functional and molecular alterations which are found in demyelinating disorders in both the optic nerves and chiasm and also these alterations were coming back to level of control animal on 28 days post lesion, which is typically seen in myelin repair process. The present paper provides new insights into the experimental toxin-induced models that may be useful for evaluating the functional recovery of demyelinated optic nerves and chiasm following various repairing strategies. It also seems to be useful for studying the protective or remyelinating effects of different therapies in e.g. optic apparatus which is more affected by MS.

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).

References (51)

  • B.G. Uzman

    The Spiral configuration of myelin lamellae

    J. Ultrastruct. Res.

    (1964)
  • S.G. Waxman et al.

    Lysophosphatidyl choline induced focal demyelination in the rabbit corpus callosum

    J. Neurol. Sci.

    (1979)
  • S.S. Zamvil et al.

    Diverse Targets for Intervention during Inflammatory and Neurodegenerative Phases of Multiple Sclerosis

    Neuron

    (2003)
  • G. Allt et al.

    Lysophosphatidyl choline-induced demyelination, a freeze-fracture study

    Acta Neuropathol (Bed)

    (1988)
  • M. Anastasi et al.

    VECPs and optic disc damage in diabetes

    Doc. Ophthalmol.

    (1987)
  • F.M. Ausubel et al.

    Short Protocols in Molecular Biology

    (2002)
  • N. Baumann et al.

    Biology of oligodendrocyte and myelin in the mammalian central nervous system

    Physiol. Rev.

    (2001)
  • R. Beck et al.

    Involvement of the optic chiasm, optic tract and geniculo-calcarine visual system in multiple sclerosis

    Bull. Soc. Belge Ophtalmol.

    (1983)
  • A. Brusa et al.

    Long-term recovery and fellow eye deterioration after optic neuritis, determined by serial visual evoked potentials

    J. Neurol.

    (1999)
  • W.M. Carroll et al.

    Experimental demyelinating optic neuropathy: a model for combined morphological and electrophysiological studies

    Clin. Exp. Neurol.

    (1983)
  • G.G. Celesia

    Evoked potentials techniques in the evaluation of visual function

    J. Clin. Neurophysiol.

    (1984)
  • K. Chiaki et al.

    Effects of narcotics, including morphine, on visual evoked potential in rats

    Eur. J. Pharmacol.

    (2009)
  • K.H. Chiappa et al.

    Evoked potentials in clinical medicine (first of two parts)

    N Engl J. Med.

    (1982)
  • V. Dousset et al.

    Lysolecithin-induced demyelination in primates: preliminary in vivo study with MR and magnetization Transfer

    AJNR Am. J. Neuroradiol.

    (1995)
  • A. Feinstein

    The Clinical Neuropsychiatry of Multiple Sclerosis, first ed

    (1999)
  • Cited by (63)

    • Cis-p-tau plays crucial role in lysolecithin-induced demyelination and subsequent axonopathy in mouse optic chiasm

      2023, Experimental Neurology
      Citation Excerpt :

      P1-wave was the first and the most stable component in VEP recording. During the demyelination phase, this wave appears later but restores to the control level by the time (Mozafari et al., 2010). P1-wave delay was evaluated as an informative index for assessing the visual pathway conductivity.

    • Nano-hesperetin enhances the functional recovery and endogenous remyelination of the optic pathway in focal demyelination model

      2020, Brain Research Bulletin
      Citation Excerpt :

      MS patients frequently experience visual disturbance. Therefore, induction of demyelination in optic tracts has been introduced as promising tool for investigating demyelination and remyelination processes (Mozafari et al., 2010; Otradovec, 1965; Vabanesi et al., 2019). Therapeutics approaches in MS mostly focus on inhibition of inflammation, increasing oligodendrocyte precursor cells (OPCs) population and their recruitment, and differentiation of OPCs toward myelin forming oligodendrocytes (OLs) (Bieber et al., 2003; McMurran et al., 2016).

    • QKI-V5 is downregulated in CNS inflammatory demyelinating diseases

      2020, Multiple Sclerosis and Related Disorders
    View all citing articles on Scopus
    1

    S. M. and M.A. S. have made same contribution in this report.

    View full text