Abstract

Cognition impairment and peripheral neuropathy (DPN) are two major complications of diabetes. The aim of the present study is to investigate the effect of sex differences on cognition and DPN in diabetic mice. Male and female BKS.Cg-m+/+Leprdb/J (db/db) and db/m mice were used. At ages of 20 and 30 weeks, all animals were subjected to learning, memory and neurological function tests. Regional blood flow in footpad and sciatic nerves were measured using laser Doppler flowmetry. Our data showed that male db/db mice aged 20 weeks and 30 weeks spent significantly more time to locate the hidden platform in the correct quadrant and spent significantly less time exploring the cage with a new stranger mouse compared to aged-matched female db/db mice. Electrophysiological recordings showed that male db mice aged 30 weeks had significantly reduced motor and sensory nerve conduction velocity compared with females. Hot plate and tactile allodynia tests revealed that males exhibited significantly higher thermal and mechanical latency than females. Male db mice aged 30 weeks displayed significantly reduced blood perfusion in sciatic nerve and footpad tissues compared with females. In addition, compared with male and female non-diabetic db/m mice, db/db mice exhibited increased time spent on locating the hidden platform, decreased time spent on exploring the novel odor bead and an unfamiliar mouse, as well as showed significantly lower levels of blood flow, lower velocity of MCV and SCV, higher thermal and mechanical latencies. Blood glucose levels and body weight were not significantly different between male and female diabetic animals (age 30 weeks), but male db mice showed a higher serum total cholesterol content. Together, our data suggest that males develop a greater extent of diabetes-induced cognition deficits and peripheral neurovascular dysfunction than females.

Highlights

  • According to the International Diabetes Federation in 2015, diabetes mellitus has become a global burden with an estimated 415 million people suffering with diabetes mellitus worldwide (IDA, 2015)

  • There was no statistical difference in blood glucose, HbA1C levels and body weight between male and female diabetic animals, but male db/db mice showed a higher serum total cholesterol content (Table 1, P < 0.0001)

  • We found that db/db mice at age of 30 weeks showed a significant reduction of blood flow in foot pad (Figure 4A) and sciatic nerve tissues (Figure 4B) measured with laser Doppler flowmetry (LDF) in male compared to female db/db mice (Figure 4)

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Summary

Introduction

According to the International Diabetes Federation in 2015, diabetes mellitus has become a global burden with an estimated 415 million people suffering with diabetes mellitus worldwide (IDA, 2015). Diabetes is associated with accelerated cognitive decline (Said, 2007; Ruis et al, 2009), in older individuals. Sex on Diabetic Cognition and Neuropathy factors, e.g., chronic hyperglycemia, hypertension, insulin resistance, and lipid disorders are pertinent determinants of diabetes driven cognitive dysfunction (Said, 2007; Ruis et al, 2009). Cognition has already been impaired at the early stage of diabetes (Ruis et al, 2009). The vast majority of patients with clinical diabetic neuropathy have a distal symmetrical form of the disorder that progresses with sensory and autonomic manifestations predominating (Said, 2007)

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