Wednesday, April 18, 2012

Slowing Hearing Loss in Diabetics and Hyperglycemics

Our Neuronal-Glial Markers are used in a variety of applications. Here our P0 or P-Zero antibody is used to show myelination levels in the cochlear ganglion. Demyelination is caused by hyperglycemia and type 2 diabetes and results in hearing loss and eventually deafness. Here's the related publication and highlights: Silvia Murillo-Cuesta, Guadalupe Camarero, Águeda González-Rodríguez, Lourdes Rodríguez-de la Rosa, Deborah J Burks, Carlos Avendaño,Ángela M Valverde and Isabel Varela-Nieto1. Insulin Receptor Substrate 2 (IRS2)-Deficient Mice Show Sensorineural Hearing Loss That Is Delayed by Concomitant Protein Tyrosine Phosphatase 1B (PTP1B) Loss of Function. Online address: doi: 10.2119/molmed.2011.00328
Highlights: The authors objective was to study the hearing function and cochlear morphology of Irs2-null mice and the impact of PTP1B deficiency. They have studied the auditory brainstem responses and the cochlear morphology of systemic Irs2–/–Ptpn1+/+, Irs2+/+Ptpn1–/– and Irs2–/–Ptpn1–/– mice at different postnatal ages. The results indicated that Irs2–/–Ptpn1+/+ mice present a profound congenital sensorineural deafness before the onset of diabetes and altered cochlear morphology with hypoinnervation of the cochlear ganglion and aberrant stria vascularis, compared with wild-type mice. Simultaneous PTP1B deficiency in Irs2–/–Ptpn1–/– mice delays the onset of deafness.

Images:  Cochlear ganglion and nerve fibers. (A–C) Cresyl violet staining of midmodiolar methacrylate sections of the cochlear ganglion at the cochlear basal turn in Irs2+/+Ptpn1+/+ (A), Irs2–/–Ptpn1+/+ (B) and Irs2–/–Ptpn1–/–mice (C) at postnatal wk 11. A slight reduction in the cellular density was more evident in both mutants (B, C) compared with wild-type (A). (D–F) Myelin P0 immunostaining of the cochlear ganglion shows less intense labeling in Irs2–/–Ptpn1+/+ (E) and Irs2–/–Ptpn1–/– (F) mice than in control mice (D). (G–I) Accordingly, myelin P0 immunostaining of nerve fibers projecting from the cochlear ganglion to the sensory cells is less intense in Irs2–/–Ptpn1+/+ and Irs2–/–Ptpn1–/– (arrows in H and I) than in wild-type mice (G). (J–L) Similarly, a weaker neurofilament 200-kDa immunostaining is observed in Irs2+/+Ptpn1–/– (K, white arrow) and Irs2–/–Ptpn1–/– (L, white arrow) mice compared with wild-type mice (J). Scale bars: A–I, 50 μm; J–L, 75 μm.

The results presented in this study demonstrate for the first time a unique tissue-specific role of IRS2 in cochlear development and hearing function; therefore, the Irs2–/– mouse could be a novel model for the in vivo study of hearing loss associated with altered glucose metabolism. The data also suggest that modulation of PTP1B activity could be a pharmacological target of interest for the sensory syndromes associated with diabetes.

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