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Skin keratinocyte-derived SIRT1 and BDNF modulate mechanical allodynia in mouse models of diabetic neuropathy

O'Brien, Jennifer; Niehaus, Peter; Chang, Koping; Remark, Juliana; Barrett, Joy; Dasgupta, Abhishikta; Adenegan, Morayo; Salimian, Mohammad; Kevas, Yanni; Chandrasekaran, Krish; Kristian, Tibor; Chellappan, Rajeshwari; Rubin, Samuel; Kiemen, Ashley; Lu, Catherine Pei-Ju; Russell, James W; Ho, Cheng-Ying
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. The same phenomenon was also noted in skin-keratinocyte specific BDNF knockout mice. Furthermore, overexpression of SIRT1 in skin induced Meissner corpuscle reinnervation and regeneration, resulting in significant improvement of diabetic mechanical allodynia. Overall, the findings suggested that skin-derived SIRT1 and BDNF function in the same pathway in skin sensory apparatus regeneration and highlighted the potential of developing topical SIRT1-activating compounds as a novel treatment for diabetic mechanical allodynia.
PMID: 38554393
ISSN: 1460-2156
CID: 5645392

Benign Paroxysmal Positional Vertigo in 2 Children: A Case Series [Case Report]

Fay, Jennifer L
PURPOSE:The purpose of this case report is to present the cases of 2 boys with benign paroxysmal positional vertigo (BPPV). KEY POINTS:Patient A (11 years old) and Patient B (9 years old) had complaints of vertigo with position changes. Both exhibited left torsion upbeating nystagmus in the left Dix-Hallpike (DH) test and complaints of vertigo with reproduction of their symptoms, indicating BPPV. Both were treated with a left canalith repositioning maneuver and reported decreased incidence of positional vertigo upon reevaluation. Scores on the Dizziness Handicap Inventory and the Visual Analog Scale for Dizziness decreased after treatment for 1 of the boys. CONCLUSION:Benign paroxysmal positional vertigo is considered rare in children. Migraines may also cause vertigo. Differential diagnosis in these cases was made by performing the DH test. RECOMMENDATIONS FOR CLINICAL PRACTICE:Children with vertigo should be screened for BPPV through use of history taking, and the DH test.
PMID: 26986871
ISSN: 1538-005x
CID: 3503342