The role of cellular senescence in neurodegenerative diseases

Neurodegenerative diseases are central and peripheral nervous system catastrophes with irreversible neuronal and glial losses. Although these diseases share cell destruction as a common denominator, each of them manifests with different clinical findings. One of the important features of neurodegenerative diseases is the silent progression of the pathological changes affecting the cells for decades before the clinical findings appear. Cellular senescence is a cell cycle arrest response that may occur due to physiological, various stress factors and/or aging and prevents the cell from entering proliferative pathways. Since cellular senescence affects the outcome of various physiological and pathological processes, its effect on neurodegeneration is under investigation. We aimed to examine behavioral and immunohistochemical changes caused by l-methioninine in order to examine insidious cellular modifications and cognitive, affective and motor function changes accompanying neurodegenerative diseases. Compared to the controls, we observed hippocampus dependent spatial memory damage, hippocampocortical network dependent learning and memory impairment and motor dysfunctions. In immunohistochemical analysis, we observed changes in senescent astrocyte densities in the dentate gyrus and CA3 which play a role in creating spatial memory and processing/separation of afferent inputs. Parallel to motor dysfunctions observed in the behavior tests of male group; we observed statistically significant differences in senescent neuron densities in layers V. and VI. in the somatosensory and primary motor cortex, respectively. Our results draw attention to the selective vulnerability of different brain areas to l-methionine. This neuroanatomical vulnerability may differ between sexes. Cellular senescence response accompanying memory and motor dysfunctions is also thought to be related to neurodegeneration.