Investigation of the Effect of Dual Deletion andPharmacological Inhibition of RhoGTPases Rac1 and Rac3on Dendritic Spine Dysgenesis in a Diabetic PeripheralNeuropathy Model: Preliminary Data

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Çalış G., Kantarcı M. A., Çelik A., Diril M. K., Esmen K., Ural Özkan C., ...Daha Fazla

Turkish Society of Physiological Sciences, 50th Turkish Physiology Congress, Antalya, Türkiye, 12 - 16 Kasım 2025, cilt.242, sa.70212, ss.66, (Özet Bildiri)

  • Yayın Türü: Bildiri / Özet Bildiri
  • Cilt numarası: 242
  • Doi Numarası: 10.1111/apha.70212
  • Basıldığı Şehir: Antalya
  • Basıldığı Ülke: Türkiye
  • Sayfa Sayıları: ss.66
  • Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
  • Dokuz Eylül Üniversitesi Adresli: Evet

Özet

AIM: Diabetic Peripheral Neuropathy (DPN) is a commoncomplication of diabetes, causing a decrease in quality oflife. Neuropathic pain is associated with structural changesin dendritic spines. Rac1 and Rac3, which are small GTPases,and PAK1, their effector molecule, are critical proteins thatregulate the morphology of dendritic spines. This studyinvestigates the roles of Rac1, Rac3, and PAK1 in DPNpathogenesis to determine potential treatment objectives.METHODS: To induce the DPN model, leptin knock-out (KO)C57BL/6 obese (ob/ob) male mice were used. Animals arerandomly assigned to 6 groups (n=10/group): 1) wt/wtcontrol, 2) ob/ob control, 3) ob/ob + Romidepsin (PAK1inhibitor) 1 mg/kg, 4) ob/ob + romidepsin 5 mg/kg, 5) ob/ob+ AAV6-GFP, 6) ob/ob + AAV6-CRE. Dynamic PlantarAesthesiometer (DPA), Hot Plate, Rotarod, Grip Strengthand Open Field tests were used at the beginning (6-7thweeks) and at the end of the study (11- 12th weeks) toassess neuropathy. Dendritic and cellular changes will beevaluated by histological and molecular analyses in thesciatic nerve, dorsal root ganglia and dorsal horn neurontissues.RESULTS: Behavioural tests of wt/wt and ob/ob controlgroups have been completed, and tissue samples have beentaken. It was shown that sensory neuropathy and anxiety-like behaviours were developed in ob/ob mice (p <0.05). Inob/ob mice, mechanical allodynia was demonstrated byDPA, and thermal hypoalgesia was demonstrated by theHot Plate test. In the Open Field test, ob/ob mice spent lesstime in the centre zone and showed diminished locomotoractivity (p<0.0001).CONCLUSIONS: Ob/ob mice have developed mechanicalallodynia, thermal hypoalgesia, and anxiety-like behavioursassociated with DPN. These findings support the successfulimplementation of the DPN model. Samples taken forhistological and molecular analyses will be studied after allgroups are completed.This study is supported by TÜSEB (Project No: 40758).