Dataset Information

Hair pyrrole adducts serve as biomarkers for peripheral nerve impairment induced by 2,5-hexanedione and n-hexane in rats.

ABSTRACT: Pyrrole adducts are specific reaction products of 2,5-hexadione (2,5-HD) in vivo and are considered highly relevant to the pathogenesis of peripheral nerve impairments after exposure to n-hexane, though the exact mechanism remains unclear. In this study, 40 male Wistar rats were randomly divided into three experimental groups and one control group, in which all rat's hair were shaved completely at the beginning. The rats in three experimental groups were treated with 2,5-HD by gavage at dosages of 100, 200 and 300 mg/kg per day respectively, six times per week for 8 weeks. Abnormality of gait and changes in the rota-rod latency were surveilled. Pyrrole adducts in hair, urine and serum of all rats were measured at the endpoint. Results showed that the increased pyrrole adducts in hair, urine and serum accumulated in dose-response relationship. Spearman's correlation analysis between pyrrole adducts and gait scores showed that hair pyrrole adducts were highly relevant to the gait scores. Moreover, we treated rats with n-hexane and succeed to verify the results aforesaid. Further, multiply linear regression analysis showed that hair pyrrole adducts have higher partial correlation coefficients than these in serum and urine in both 2,5-HD and n-hexane treated models. Our findings draw the conclusion that the hair pyrrole adducts might serve as a promising biomarker of n-hexane induced peripheral neuropathy.

SUBMITTER: Li X

PROVIDER: S-EPMC6312332 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Hair pyrrole adducts serve as biomarkers for peripheral nerve impairment induced by 2,5-hexanedione and n-hexane in rats.

Li Xianjie X Wang Qiong Q Li Ming M Wang Shuo S Zhang Cuiqin C Xie Keqin K

PloS one 20181231 12

Pyrrole adducts are specific reaction products of 2,5-hexadione (2,5-HD) in vivo and are considered highly relevant to the pathogenesis of peripheral nerve impairments after exposure to n-hexane, though the exact mechanism remains unclear. In this study, 40 male Wistar rats were randomly divided into three experimental groups and one control group, in which all rat's hair were shaved completely at the beginning. The rats in three experimental groups were treated with 2,5-HD by gavage at dosages ...[more]

PMID: 30596762

Similar Datasets

Project description:Dysfunction of the peripheral auditory nerve (AN) contributes to dynamic changes throughout the central auditory system, resulting in abnormal auditory processing, including hypersensitivity. Altered sound sensitivity is frequently observed in autism spectrum disorder (ASD), suggesting that AN deficits and changes in auditory information processing may contribute to ASD-associated symptoms, including social communication deficits and hyperacusis. The MEF2C transcription factor is associated with risk for several neurodevelopmental disorders, and mutations or deletions of MEF2C produce a haploinsufficiency syndrome characterized by ASD, language, and cognitive deficits. A mouse model of this syndromic ASD (Mef2c-Het) recapitulates many of the MEF2C haploinsufficiency syndrome-linked behaviors, including communication deficits. We show here that Mef2c-Het mice of both sexes exhibit functional impairment of the peripheral AN and a modest reduction in hearing sensitivity. We find that MEF2C is expressed during development in multiple AN and cochlear cell types; and in Mef2c-Het mice, we observe multiple cellular and molecular alterations associated with the AN, including abnormal myelination, neuronal degeneration, neuronal mitochondria dysfunction, and increased macrophage activation and cochlear inflammation. These results reveal the importance of MEF2C function in inner ear development and function and the engagement of immune cells and other non-neuronal cells, which suggests that microglia/macrophages and other non-neuronal cells might contribute, directly or indirectly, to AN dysfunction and ASD-related phenotypes. Finally, our study establishes a comprehensive approach for characterizing AN function at the physiological, cellular, and molecular levels in mice, which can be applied to animal models with a wide range of human auditory processing impairments.SIGNIFICANCE STATEMENT This is the first report of peripheral auditory nerve (AN) impairment in a mouse model of human MEF2C haploinsufficiency syndrome that has well-characterized ASD-related behaviors, including communication deficits, hyperactivity, repetitive behavior, and social deficits. We identify multiple underlying cellular, subcellular, and molecular abnormalities that may contribute to peripheral AN impairment. Our findings also highlight the important roles of immune cells (e.g., cochlear macrophages) and other non-neuronal elements (e.g., glial cells and cells in the stria vascularis) in auditory impairment in ASD. The methodological significance of the study is the establishment of a comprehensive approach for evaluating peripheral AN function and impact of peripheral AN deficits with minimal hearing loss.

Dataset Information

Hair pyrrole adducts serve as biomarkers for peripheral nerve impairment induced by 2,5-hexanedione and n-hexane in rats.

Publications

Hair pyrrole adducts serve as biomarkers for peripheral nerve impairment induced by 2,5-hexanedione and n-hexane in rats.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets