Automated compartment-based quantification reveals distinct patterns of cutaneous innervation with aging and microbial colonization
Cutaneous innervation is commonly quantified using measures such as intraepidermal nerve fiber density, but these approaches capture only selected anatomical regions or features of nerve structure. We developed an automated image-analysis pipeline to quantify nerve area and nerve-skeleton length across defined epidermal and dermal compartments in whole, stitched mouse plantar skin sections.…
Quantifying the intricate network of nerves in the skin has traditionally relied on measuring a single aspect, such as the density of nerve fibers within the epidermis. However, this approach overlooks the complexities of both the epidermis and dermis layers. To address this limitation, researchers have devised an automated image-analysis pipeline capable of quantifying nerve area and nerve-skeleton length across distinct compartments in both skin layers of mouse plantar skin sections.
The automated pipeline proved to be highly accurate, with its boundary detection of the epidermis-dermis junction aligning well with manual tracing, even within the range of inter-observer variation. This consistency enabled the pipeline to generate comparable downstream measurements.
The researchers then put this pipeline to the test on skin samples from mice subjected to different conditions. When exposed to a microbial environment, the mice exhibited a significantly higher nerve area and length in both the epidermis and dermis compared to germ-free counterparts. This observation was consistent across different ages of mice.
In contrast, the aging cohort revealed an increase in dermal nerve area and length compared to their younger counterparts, while no significant differences were observed in the epidermal measurements. When considering the skin as a whole, the nerve area and length were greater in the conventionalized (microbe-exposed) mice compared to the germ-free mice, but no significant differences were found between the young and aged mice when both skin layers were analyzed together.
These findings underscore the importance of compartment-resolved quantification in unraveling the nuances of cutaneous innervation. By analyzing the epidermis and dermis separately, this approach enables the identification of nerve measurements that may go unnoticed when both layers are examined collectively. Consequently, compartment-resolved quantification offers a valuable complementary method for studying alterations in skin innervation across various biological conditions and behavioral outcomes.
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