Senescence Associated With Neurodegeneration: Simultaneous Assessment of β-gal Activity And Nissl Stain In...

Cellular senescence is a physiological process characterized by irreversible cell cycle arrest that impairs tissue regeneration and function. This phenomenon has emerged as a key driver of neurodegeneration, fueled by the accumulation of senescent cells within the central nervous system (CNS). Senescent cells acquire a pro-inflammatory senescence-associated secretory phenotype (SASP) that sustains chronic neuroinflammation and disrupts the neuronal microenvironment. Consequently, essential processes such as neurogenesis, synaptic plasticity, and neuronal survival are compromised. An extensive body of literature associates cellular senescence with several neurodegenerative disorders, such as Parkinson's disease, Alzheimer's disease, or multiple sclerosis, and acute neuronal-related damage, such as cerebral ischemia or traumatic brain injury. The combined assessment of senescence-associated β-galactosidase (SA-β-gal) activity and Nissl staining in histological sections provides a comprehensive approach to evaluate cellular senescence and neuronal integrity simultaneously within the same tissue context. This strategy enables precise spatial correlation between the accumulation of senescent cells in specific vulnerable regions (e.g., the hippocampus or cortex) and neuronal loss or tissue damage. By integrating a functional marker of senescence with a classical indicator of neuronal morphology and density, this approach strengthens the interpretative robustness of the analysis. Moreover, it enables a more accurate characterization of the relationship between senescent burden and neurodegenerative changes, maximizing the information yield from limited tissue samples. Moreover, this protocol can determine how senescent cell accumulation occurs in response to interventions (pharmacological, genetic manipulation, etc.) in rodent models of neurodegenerative diseases, thereby providing a powerful tool to analyze this contribution to their pathophysiology.