Synaptic Structural Dynamics and Aging

Abstract

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.

Increased phosphorylation of the neuronal L-type Ca 2+ channel Ca v 1.2 during aging

“…The number of synaptic contacts is reduced in the aging mammalian brain (85)(86)(87)(88). If increased L-type channel activity impairs neuronal functions by contributing to synaptic loss during aging, up-regulation of L-type channels should occur before a significant reduction in the number of synapses.…”

Lack of serotonin1B receptor expression leads to age-related motor dysfunction, early onset of brain molecular aging and reduced longevity

“…Aging leads to morphological [1][2][3][4][5] and functional [6][7][8][9] changes in the brain and is associated with increased risk for psychiatric and neurological disorders. [10][11][12][13] However, the mechanisms underlying normal aging of the brain likely differ from those associated with neurodegenerative and pathological conditions and are still poorly understood.…”

Dietary restriction modulates synaptic structural dynamics in the aging hippocampus

“…An interpretation of these findings is in order. Despite well differentiated zones of the nerve cell terminal regions, synaptic junctions are widely reported to be very plastic structures capable of relevant structural remodelling processes (15)(16)(17)(18)(19). Quantitative estimations of the dynamic morphology of the synapticjunctional areas are currently carried out by evaluating functional ultrastructural features.…”

“…Considering tenable explanations of these effects of dietary restriction on the synaptic adaptive potential, it must be mentioned that current knowledge of synaptic functional morphology hypothesizes an ordered sequence of steps occurring in the structural rearrangements of the junctional areas (15,16,19,29). As a consequence of stimulation, the sequence is as follows: synaptic contact zones (I) enlarge, (11) perforate and (111) split to yield an increased number of smaller contacts.…”

“…The hippocampi were rapidly excised, sectioned in 500pm thickness slices by a Mac IIIwain tissue chopper and stained for synaptic junctional areas by means of the ethanol phosphotungstic acid preferential technique (E-PTA) (Fig. I) according to our previous papers (15,(20)(21)(22). Morphometry.…”