In vivo skin leptin modulation after 14 MeV neutron irradiation: a molecular and FT-IR spectroscopic study

Abstract

This paper discusses gene expression changes in the skin of mice treated by monoenergetic 14 MeV neutron irradiation and the possibility of monitoring the resultant lipid depletion (cross-validated by functional genomic analysis) as a marker of radiation exposure by high-resolution FT-IR (Fourier transform infrared) imaging spectroscopy. The irradiation was performed at the ENEA Frascati Neutron Generator (FNG), which is specifically dedicated to biological samples. FNG is a linear electrostatic accelerator that produces up to 1.0 × 10(11) 14-MeV neutrons per second via the D-T nuclear reaction. The functional genomic approach was applied to four animals for each experimental condition (unirradiated, 0.2 Gy irradiation, or 1 Gy irradiation) 6 hours or 24 hours after exposure. Coregulation of a subclass of keratin and keratin-associated protein genes that are physically clustered in the mouse genome and functionally related to skin and hair follicle proliferation and differentiation was observed. Most of these genes are transiently upregulated at 6 h after the delivery of the lower dose delivered, and drastically downregulated at 24 h after the delivery of the dose of 1 Gy. In contrast, the gene coding for the leptin protein was consistently upregulated upon irradiation with both doses. Leptin is a key protein that regulates lipid accumulation in tissues, and its absence provokes obesity. The tissue analysis was performed by monitoring the accumulation and the distribution of skin lipids using FT-IR imaging spectroscopy. The overall picture indicates the differential modulation of key genes during epidermis homeostasis that leads to the activation of a self-renewal process at low doses of irradiation.