Neuronal involution during ageing. Ultrastructural study in the rat cerebellum.

Abstract

Involutive phenomena have been investigated by electron microscopy in the Purkinje Pk neuron of the cerebellar cortex of the aging rat. The still limited number of specimens available to date, however, suggest an age-related progression of morphological and functional deteriorations involving particularly the intraneuronal "nucleus-ribosome system" (NRS). The impairments are characterized by changes in the nucleolar texture. These alterations are accompanied by modifications in the repartition and relative proportion of RNP components of the nucleolus. In addition, other nuclear elements such as interchromatin and perichromatin granules may vary in importance with age. Recognizable changes in the ribosomal constituents of the NRS are evidenced by modifications in the density and distribution of free ribosomes. An altered structure and organization of GER cisternae are also evident. Furthermore, "light" cytoplasmic areas, an increased evidence of neurotubules and the gradual congestion of the pericaryon by age pigments are other valuable ultrastructural features that may be regarded as part of the sequence of morphologic events occurring during neuonal ageing. The above ultrastructural data will subsequently form the basis of a model of ageing in the nerve cell, which will complete the previously proposed model of neuronal maturation. Therefore, this long-term study essentially purports the investigation of subcellular events taking place in the Pk neuron all along the normal life span in rats. This model will also be used to evaluate the changes in the sequence and the reinforcement of the processes of evolution versus involution as affected by certain xenobiotics, such as abused drugs(alcohol and narcotics). The intraneuronal modifications found in the nuclear and cytoplasmic structures of the NRS could possibly reflect the molecular dysfunction related to the production of various types of RNA and neuronal proteins. This hypothesis is supported by biochemical data obtained from analysis of the brain of aged animals. Ultrastructural and biochemical data appear to be in good agreement with the neurophysiologic interpretation of a slow-down and reduced efficiency of the CNS during the progressive development of senescence in human and animal subjects.