Comparing axon regeneration in male and female mice after peripheral nerve injury

Abstract

Axons in the adult mammalian central nervous system fail to regenerate after injury. By contrast, spontaneous axon regeneration occurs in the peripheral nervous system (PNS) due to a supportive PNS environment and an increase in the intrinsic growth potential induced by injury via cooperative activation of multifaceted biological pathways. This study compared axon regeneration and injury responses in C57BL/6 male and female mice after sciatic nerve crush (SNC) injury. The extent of axon regeneration in vivo was indistinguishable in male and female mice when observed at 3 days after SNC injury, and primary dorsal root ganglion (DRG) neurons from injured, male and female mice extended axons to a similar length. Moreover, the induction of selected regeneration‐associated genes (RAGs), such as Atf3, Sprr1a, Gap43, Sox11, Jun, Gadd45a, and Smad1 were comparable in male and female DRGs when assessed by quantitative real‐time reverse transcription polymerase chain reaction. Furthermore, the RNA‐seq analysis of male and female DRGs revealed that differentially expressed genes (DEGs) in SNC groups compared to sham‐operated groups included many common genes associated with neurite outgrowth. However, we also found that a large number of genes in the DEGs were sex dependent, implicating the involvement of distinct gene regulatory network in the two sexes following peripheral nerve injury. In conclusion, we found that male and female mice mounted a comparable axon regeneration response and many RAGs were commonly induced in response to SNC. However, given that many DEGs were sex‐dependently expressed, future studies are needed to investigate whether they contribute to peripheral axon regeneration, and if so, to what extent.

Nerve Transfers for Brachial Plexus Reconstruction in Patients over 60 Years

“…In our series, four of five patients were male, which reflects the gender disbalance of brachial plexus injuries, which mainly affect men [15]. Even though the literature suggests a pro-regenerative effect of androgen hormones in nerve regeneration, there is no clear evidence for superior results in males [24][25][26]. For evaluation of a clinical gender difference in peripheral nerve regeneration a bigger cohort with a representative number of female patient would be necessary.…”

Comprehensive cornified envelope protein profile of odontogenic keratocysts clarifies the characteristics of non‐keratinized oral epithelium

“…TG1, TG3, and their substrates are localized in the epidermis or oral mucosal epithelium and contribute to the formation of CE during the differentiation of the epidermis or oral mucosal epithelium 8 . Although some investigators reported mRNA expressions of TG1, SPRR1a, and SPRR3 in large vessels such as the aorta and vena cava, injured peripheral nerve, and atherosclerotic vessels, respectively, the mRNA expressions were described in limited cells and pathological conditions 28–30 . Thus, our method can scarcely interfere with our mRNA expression results.…”

“…8 Although some investigators reported mRNA expressions of TG1, SPRR1a, and SPRR3 in large vessels such as the aorta and vena cava, injured peripheral nerve, and atherosclerotic vessels, respectively, the mRNA expressions were described in limited cells and pathological conditions. [28][29][30] Thus, our method can scarcely interfere with our mRNA expression results.…”

The Dynamics of Nerve Degeneration and Regeneration in a Healthy Milieu and in Diabetes

“…Although most nerve injuries in humans affect males, few studies have concentrated on investigating nerve regeneration mechanisms in male and female rats or mice in clinically relevant injury and repair and reconstruction models [30,[145][146][147][148]. Gender-specific perspectives are relevant in view of reported enhancement of axonal outgrowth in males, and sustained synaptic inputs by exercise are observed in male and female rats, but the requirements of exercise protocols differ between sexes [30,[145][146][147][148].…”

“…Although most nerve injuries in humans affect males, few studies have concentrated on investigating nerve regeneration mechanisms in male and female rats or mice in clinically relevant injury and repair and reconstruction models [30,[145][146][147][148]. Gender-specific perspectives are relevant in view of reported enhancement of axonal outgrowth in males, and sustained synaptic inputs by exercise are observed in male and female rats, but the requirements of exercise protocols differ between sexes [30,[145][146][147][148]. In contrast to studies examining gender effects on nerve regeneration after a nerve crush, axonal outgrowth seems to be better in healthy and diabetic male rats than in corresponding healthy and diabetic female rats after a sciatic nerve injury and direct repair [30].…”