Activity of 2′, 3′-Cyclic Nucleotide 3′-Phosphodiesterase (CNPase) in Spinal Cord with Spongy Change Induced by a Single Oral Dose of Aniline in Rats

Abstract

A spongy change in the spinal cord white matter was observed in four-week-old rats treated with aniline. Although this change was found to be a result of the myelin sheath splitting at the ultrastructural level, the mechanism is unknown. This study was conducted to identify the mechanism of the spongy change in aniline-treated rats. The spongy change in the spinal cord white matter was first detected on day 5 in the histopathologic examination. The incidence and severity of the lesions, especially in the lateral and ventral funiculi of the thoracic spinal cord white matter, increased prominently from day 8 to day 10. In all rats, immunohistochemical staining by anti-2 0 , 3 0 -cyclic nucleotide 3 0 -phosphodiesterase (CNPase) occurred along the cytoplasmic boundaries of the normal oligodendroglia. However, mild to moderate anti-CNPase staining extended to the swollen cytoplasm of the oligodendroglia in the aniline-treated rats from day 2 to day 4. In the electron microscopic examination, free ribosomes and rough endoplasmic reticula in the cytoplasm of the oligodendroglia increased on days 3 and 4. These changes were considered to be related to CNPase expression. However, CNPase expression decreased, whereas the spongy changes were detected from day 5. The reduction in CNPase expression may contribute to the changes in the myelin morphology observed in aniline intoxication.

Hexachlorophene and Cuprizone Induce the Spongy Change of the Developing Rat Brain by Different Mechanisms: The Role of 2’, 3’-Cyclic Nucleotide 3’-Phosphodiesterase (CNPase)

“…Strong CNPase positive reaction was not observed in the white matter, where degeneration of oligodendroglia and the spongy change were present in both HCP-and CPZ-treated rats. We previously reported that aniline induces the spongy change in the white matter of the spinal cord, which is accompanied by strong CNPase immunoreaction in the gray matter but not the white matter [11]. The reason for this is unknown why CNPase immunoreaction of oligodendroglia only in the gray matter.…”

“…The severity of the spongy change and the degree of antiCNPase immunostaining were designated at grades 4 and 3 [11], respectively, and temporally evaluated as follows: A. The spongy change: score=0, not detectable (−); score=1, small vacuoles scattered in the white matter (+); score=2, small or middle vacuoles diffusely present in the white matter (++); score=3, large vacuoles massively present in the white matter (+++).…”

“…Furthermore, CNPase provides a marker of oligodendroglia differentiation because it localizes to the periaxonal region of the myelin sheath and oligodendroglial cell membranes [24]. We have been able to demonstrate a single dose of aniline induces the spongy change, which can be detected by light microscopy, and that CNPase activity peaks before its onset [11]. However, the role of CNPase during cytotoxic insults to oligodendroglia or the myelin sheath is still unknown.…”

Closantel; a veterinary drug with potential severe morbidity in humans

“…Myelin splitting as a result of some exogenous or endogenous substances intoxication such as nitrobenzene is a well-described condition in sheep and goats [2, 9, 10]. Nitrobenzene which acts by uncoupling of mitochondrial Phosphorylation results in similar changes in oligodendrocytes [11].…”

Perinatal methylmercury exposure perturbs the expression of Plp1 and Cnp splice variants in cerebellum of rat pups

“…The mRNA or protein levels of oligodendrocyte-enriched genes, such as Mbp (Padhi and Pelletier, 2012), Plp1 and Cnp can be useful biomarkers to assess perturbation of myelination. Perturbation of Plp1 gene expression was observed following exposure to cocaine (Kristiansen et al, 2009), nicotine (Cao et al, 2013), propylthiouracil (Kobayashi et al, 2009), while alteration of Cnp expression was observed after treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (Fernandez et al, 2010), aniline, cuprizone and hexachlorophene (Kanno et al, 2010(Kanno et al, , 2012. By the use of alternative promoters and alternative splicing, a gene can produce multiple transcript variants , which may have different and even antagonistic functional roles (Menon et al, 2011).…”