Changes in the immunoreactivity of protein gene product (PGP) 9.5 in the cochlea of spontaneously diabetic WBN/Kob rats

Abstract

In our previous study, hearing impairment of spontaneously diabetic WBN/Kob rats was first detected as an elevation of the hearing threshold in the auditory brainstem response in animals expressing glucose intolerance, then as a decrease in the number of spiral ganglion cells in the cochlea, and finally as oedematous changes in the stria vascularis [1]. Atrophy of the spiral ganglion was also reported as the most common pathological change in the cochlea of diabetic patients [2]. On the other hand, functional changes in the spiral ganglion cells caused by diabetes mellitus remain to be examined.Protein gene product (PGP) 9.5 is a ubiquitin carboxyl-terminal hydrolase [3] prevalent in cells of neural origin [4][5][6]. Although the functional significance of PGP 9.5 is still unclear, this protein may play an essential role in the ubiquitin-related metabolism in nervous tissues. Recently, PGP 9.5 has been increasingly used as a convenient neural marker in neurophysiological studies [7][8][9][10][11][12]. In the present study, therefore, we examined the immunoreactivity for PGP 9.5 in the spiral ganglion cells of the cochlea in prediabetic and diabetic WBN/Kob rats by an immunohistochemical method with computer-assisted image analysis and compared the results with those obtained from normal age-matched Wistar rats in order to reveal the functional changes in the spiral ganglion cells from a quantitative point of view. Diabetologia (1997) 40: 173-178 Changes in the immunoreactivity of protein gene product (PGP) 9.5 in the cochlea of spontaneously diabetic WBN/Kob rats Summary The mechanism of hearing impairment due to diabetes mellitus was examined in relation to changes in the level of the immunoreaction for the protein gene product 9.5 in the cochlea of spontaneously diabetic WBN/Kob rats. At 7 months (33 weeks) of age, when half of the males of this strain manifest diabetes, male WBN/Kob rats were divided into two groups as follows: one group consisted of prediabetic animals showing slightly decreased tolerance to glucose with a normal plasma concentration of glucose, normal urinary excretion of glucose, and functional hearing impairment (assessed in terms of elevation of hearing threshold). The second group consisted of diabetic animals with glucose intolerance, high plasma glucose level, polyuria, urinary glucose excretion, and more apparent elevation of hearing threshold. According to morphometric analysis of the spiral ganglion, the number of ganglion cells was significantly smaller in both the prediabetic and the diabetic animals than in the age-matched control Wistar rats. The staining intensity for protein gene product 9.5 was increased in some spiral ganglion cells of diabetic animals, but decreased in others according to quantitative immunohistochemical analysis. On the other hand, the immunoreactivity for protein gene product 9.5 was similar in the prediabetic animals to that in the control Wistar rats. These results suggest that numerical and immunohistochemical changes in the spiral ganglion cells r...

Diabetes and cardiovascular autonomic dysfunction: Application of animal models

“…There is no information on the status of cardiovascular autonomic reflexes; however, there is data which shows sensory and motor neuropathies in the WBN/Kob model. Hearing impairment occurs with aging and is associated with sensory nerve degeneration, indication of somatic neuropathy (Ishikawa et al , 1995;Ishikawa et al , 1997). Diabetic motor neuropathy was characterized by medullary sheath degeneration and demyelination, similar to changes observed in diabetic patients, but not seen in STZ diabetes (Ozaki et al , 1996).…”

Sub-clinical auditory neural deficits in patients with type 1 Diabetes Mellitus

“…Histopathological examination found a decrease in the number of spiral ganglion cells and oedematous change in the SV. Using the same methods, Ishikawa et al (1997) reported similar results with higher hearing thresholds and a reduced number of spiral ganglion cells. Additionally, immune-histochemical examination showed that immunoreactivity for protein gene product (PGP) 9.5, a protein that may play a role in ubiquitin-related metabolism in nervous tissues, was negative in 30% of the spiral ganglion neurons.…”

“…Significant OHC loss was noted in the DM obese animals compared to the control obese. Ishikawa et al (1995Ishikawa et al ( , 1997 used WBN/Kob rats derived from Wistar rats (Kobori et al, 1977) which spontaneously develop diabetes due to endocrine-exocrine pancreatic insufficiency (Nakama et al, 1985;Ohashi et al, 1990). In Ishikawa et al (1995) 20 WBN/Kob rats had ABR recordings at three, six-seven, and 12-13 months, then a few days later the temporal bones including the inner ear were dissected and examined.…”

“…PGP 9.5 is a neuron-specific protein found in the nerves of mammals (Doran et al, 1983;Lundberg et al, 1988;Properzi et al, 1993) and is uniformly distributed in the cytosol and nucleoplasm as a soluble protein in the spiral ganglion cells of the cochlea (Yamashita et al, 1991;Baxter et al, 1993). Ishikawa et al (1997) have suggested that this decreased immunoreactivity for anti-PGP 9.5 serum may reflect structural and functional changes of these cells. McQueen et al (1999) examined the basement membrane of the SV of 48 spontaneously hypertensive-corpulent non-insulin-dependent rats.…”

Pentoxifylline response in alloxan-induced diabetic rats

“…Neural damage consists of loss of ganglion cells and demyelination of the VIIIth nerve sheath [12,13]. These changes cause a delay in central transmission time [5].…”