Constant Light Versus Intermittent Constant Light/Recovery Regimen: Differential Effects on Pineal Ultrastructure, Clock Gene Protein Abundance, and Systemic Metabolism in Rats

Disruption of the natural light regimen is considered a key pathogenetic factor in the development of desynchronosis and associated diseases. The pineal gland, as a neuroendocrine organ, is a central component of the circadian system and the primary target of the pathogenic effects of disrupted lighting. However, it remains unclear whether the mechanisms of pineal damage differ between different types of light stress. In this study, 120 male Wistar rats underwent a comprehensive analysis of the morphofunctional state of the pineal gland under two lighting regimens: constant lighting and intermittent constant light. Using light and electron microscopy, immunohistochemistry, ELISA, and cosinor analysis, it was established that the two regimens induce qualitatively different types of light stress. The obtained data indicate that constant lighting induces a degenerative phenotype with loss of rhythmic organization, whereas the shift regimen produces a phenotype of chronic re-adaptation with hyperactivation of the lysosomal system, paradoxical overexpression of clock genes, and pronounced metabolic disturbances. The identified differential markers may serve as a basis for preclinical evaluation of the efficacy of chronobiotic therapy and for the development of prevention strategies for disorders associated with shift work and light pollution.