Sex-dependent Aβ RA-Low threshold mechanoreceptors alteration in diabetic conditions

Diabetic peripheral neuropathy (DPN) is a major complication of diabetes that profoundly affects quality of life, yet its cellular mechanisms remain poorly defined. Neuropathic pain and sensory loss in DPN are thought to arise from progressive alterations in peripheral nerves usually described as a glove-stocking distribution, but the specific contribution of sensory neuron subtypes has received little attention. Here, we focused on A{beta} rapidly adapting low-threshold mechanoreceptors (A{beta} RA-LTMRs), a large-diameter sensory neuron subtype best known for mediating touch and vibratory sensation. Using an intersectional genetic approach, we generated AdvillinCre; MafAFlpO; Ai65 mice, allowing us to selectively label MafA-expressing sensory neuronal populations, which we identified as A{beta} RA-LTMRs. We provide the first detailed characterization of how diet-induced type 2 diabetes alters A{beta} RA-LTMRs. After 16 weeks of high-fat diet (HFD), we observed striking sex-dependent effects. Male mice developed impaired glucose tolerance, mechanical hypoalgesia, and thermal hyperalgesia, which correlated with a decrease of A{beta} RA-LTMR central projections in the dorsal horn. By contrast, female mice showed no changes in either their glycemic status or their sensory sensitivity. These findings demonstrate that A{beta} RA-LTMRs are vulnerable to early diabetes-induced alterations in a sex-dependent manner and highlight distinct peripheral versus central mechanisms contributing to sensory dysfunction.