Jennifer O'Brien, Peter Niehaus, Koping Chang, Juliana Remark, Joy Barrett, Abhishikta Dasgupta, Morayo Adenegan, Mohammad Salimian, Yanni Kevas, Krish Chandrasekaran, Tibor Kristian, Rajeshwari Chellappan, Samuel Rubin, Ashley Kiemen, Catherine Pei-Ju Lu, James W Russell, Cheng-Ying Ho
Diabetic neuropathy is a debilitating disorder characterized by spontaneous and mechanical allodynia. The role of skin mechanoreceptors in the development of mechanical allodynia is unclear. We discovered that mice with diabetic neuropathy had decreased sirtuin 1 (SIRT1) deacetylase activity in foot skin, leading to reduced expression of brain-derived neurotrophic factor (BDNF) and subsequent loss of innervation in Meissner corpuscles, a mechanoreceptor expressing the BDNF receptor TrkB. When SIRT1 was depleted from skin, the mechanical allodynia worsened in diabetic neuropathy mice, likely due to retrograde degeneration of the Meissner-corpuscle innervating Aβ axons and aberrant formation of Meissner corpuscles which may have increased the mechanosensitivity...
March 30, 2024: Brain