Synaptic junctional areas are not immutable structures, on the contrary, they are remodelled throughout the individual’s life-span as a consequence of environmental stimulations. This adaptive capacity of the synapses is discussed from a morphological standpoint with reference to aging. In old subjects, the number of contacts and the total surface area of synaptic appositions per unit volume of tissue decrease significantly, while the average synaptic size increases at a different extent according to the CNS area taken into account. This increase in synaptic average area is due to a higher percent of a subpopulation of enlarged contacts supposed to represent either the degenerating junctional zones or a compensatory phenomenon counteracting the synaptic reduction in number. Recent studies on perforated synapses support that the enlarged junctions are possible intermediates in synaptic physiological restructuring, thus the higher percentage of this type of contacts in the old CNS may witness unaccomplished synaptic turnover cycles. Taking into account the high metabolic rate of nerve cells, an age-related impairment in energy provision at synaptic terminal regions may constitute an early and subtle alteration affecting synaptic dynamic morphology in aging.

Mitochondria are topologically closed bilayered systems where the synthesis of adenosine triphosphate (ATP) from adenosine diphosphate (ADP) and inorganic phosphate occurs via oxidative phosphorylation. The ordered architecture (and its extension) of the mitochondria (i.e. inner membrane, outer membrane and cristae) constitutes a critical topographic arrangement for their energy-providing mechanisms. Thus, quantitative estimations of the ultrastructural features of organelles preferentially stained by means of function-related cytochemical reactions reliably report on their potential to supply adequate amounts of ATP. On the basis of this rationale, we carried out a computer-assisted cytochemical study of cytochrome oxidase (COX) activity on mitochondria of different size in the cerebellar cortex of adult rats. The total intra-mitochondrial area of the cytochemical precipitates (CPA)/mitochondrion, the area (MA) and the longer diameter (F max ) of COX-positive organelles were measured. The ratio (R): CPA/MA was also calculated and referred to as the percentage of mitochondrial inner membrane area involved in COX activity. The regression analysis of R vs MA showed a significant inverse correlation (r=0.905). The fourfold increase in MA from quartiles I to IV was matched by increases in F max and CPA, respectively, but it was also related to a 25% decrease in R. By matching quantitative cytochemical estimations of COX activity within mitochondria with the morphometric assessment of their ultrastructural features, the present study correlates size to the metabolic competence of COX-positive organelles. Quantitative cytochemistry of COX activity is currently regarded as a reliable marker of cellular metabolism; thus our findings support the hypothesis that enlargements in size are inversely correlated with the mitochondrial metabolic competence.

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