Gender-specific differences in diabetic neuropathy in BTBR ob/ob mice

Area of Science:

• Neuroscience
• Genetics
• Endocrinology

Background:

• Diabetic peripheral neuropathy (DPN) affects millions globally, with limited understanding of sex-specific mechanisms.
• The BTBR ob/ob mouse model is utilized to study metabolic disorders and their complications.

Purpose of the Study:

• To establish and characterize a female mouse model for diabetic peripheral neuropathy (DPN).
• To investigate gene expression profiles in the sciatic nerve (SCN) and dorsal root ganglia (DRG) of female BTBR ob/ob mice.
• To identify potential molecular mechanisms underlying DPN in females.

Main Methods:

• Phenotypic assessment included heat stimuli latency, nerve conduction velocities (NCV), and intraepidermal nerve fiber (IENF) density.
• Gene expression profiling was performed on DRG and SCN using microarray analysis.
• Differentially expressed genes and dysregulated pathways were identified.

Main Results:

• Female BTBR ob/ob mice displayed significant motor and sensory NCV deficits, comparable to males.
• Intraepidermal nerve fiber (IENF) density was reduced more in female ob/ob mice than in males.
• Transcriptional profiling revealed dysregulation of inflammation-related pathways in the peripheral nerves of female mice.

Conclusions:

• Female BTBR ob/ob mice serve as a robust model for studying diabetic peripheral neuropathy (DPN).
• Inflammation-associated pathways are significantly altered in the peripheral nervous system of female DPN models.
• These findings contribute to understanding sex differences in DPN pathogenesis.