English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Open

Diabetic peripheral neuropathy (DPN) is one of the most common diabeticcomplications. Mechanisms underlying nerve damage and sensory loss followingmetabolic dysfunction remain large unclear. Recently, hyperglycemia-inducedmitochondrial dysfunction and the generation of ROS have gained attention aspossible mechanisms of organ damage in diabetes. Hypoxia-inducible factor1(HIF1a) is a key transcription factor activated by hypoxia, hyperglycemia,nitric oxide as well as ROS, suggesting a fundamental role in DPNsusceptibility. Genetically-modified mutant mice, which conditionally lackHIF1a in peripheral sensory neurons (SNS-HIF1a-/-), were analyzedlongitudinally up to 6 months in the streptozotocin (STZ) model of type1diabetes. Behavioral measurements of sensitivity to thermal and mechanicalstimuli, quantitative morphological analyses of intraepidermal nerve fiberdensity and measurements of reactive oxygen species (ROS) in sensory neurons invivo were undertaken over several months post-STZ injections to delineate therole of HIF1a in DPN. Longitudinal behavioral and morphological analyses at 5,13 and 24 wks post-STZ treatment revealed that SNS-HIF1a-/- developed strongerhyperglycemia-evoked losses of peripheral nociceptive sensory axons associatedwith stronger losses of mechano- and heat sensation with a faster onset thanHIF1afl/fl mice. Mechanistically, these histomorphologic and behavioraldifferences were associated with significantly higher level of STZ-inducedproduction of ROS in sensory neurons of SNS-HIF1a-/- mice as compared withHIF1afl/fl. Our results indicate that HIF1a is as an upstream modulator of ROSin peripheral sensory neurons and exerts a protective function in suppressinghyperglycemia-induced nerve damage by limiting ROS levels. HIF1a stabilizationmay be thus a new strategy target for limiting sensory loss, a debilitatinglate complication of diabetes.

Hypoxia-inducible factor 1a protects peripheral sensory neurons from  diabetic peripheral neuropathy by suppressing accumulation of reactive oxygen  species