Synaptic Numeric Density

As points of communication between neurons, the synapses play different roles and are characterized by various degrees of efficacy at different locations; accordingly, their number represents the amount of neural inputs to the neurons of a CNS region. The size of the postsynaptic potential is influenced by the density of the synapses in a given tissue area or volume (Nv), and this, in turn, may significantly modulate information processing. Overproduction of synapses occurs in early developmental periods; then the synapses are pruned through competitive interactions and activity-based mechanisms in order to set up the best topographical map of synaptic connections adapted to environmental stimulations. In the fully-differentiated adult CNS, the synaptic pattern can still be modified by the growth of novel connections as a consequence of the experiential framework of each individual. In aging, loss of synaptic contacts has been reported to occur, although the extent and the statistical significance of the age-related reduction of Nv depends both on the specific vulnerability to aging of the CNS area taken into account and on the method of counting. Namely, despite the fact that the early investigations on synaptic number in aging were carried out about 25 years ago (Cotman and Scheff, 1979; Bertoni-Freddari and Giuli,

1980), there is still no consensus on the criteria for counting them unbiasedly, and this has yielded a consistent amount of sometimes contradictory data (Genisman et al., 1995). Profile counts, assumption-based methods, serial reconstructions, and stereological methods are the procedures that have been used to estimate the number of synapses in tissue sections, and the criteria for these methods are different, thus resulting in a marked variability of data.

In the early 1980s, the introduction of the disector as a sterological procedure for counting objects in tissue sections (Sterio, 1984) resulted in a complete break from the previous methods of counting; now this procedure is becoming the method of choice in the estimation of synaptic number because it is unbiased and easy to use. The dissector may be defined as a three-dimensional stereological probe composed of pairs of sections: the reference section and a serial section called the look-up section. The volume of the disector is determined by the area of the sections and the distance between them. Objects are considered to be in the disector and counted if they can be identified in the look-up section, but not in the reference one. In order to detect all the objects to be counted, the distance between reference and look-up sections must be less than the shortest dimension of the objects; with specific reference to synaptic counts, adjacent sections can be used, and they must be located randomly within a given neural region (Bertoni-Freddari et al., 2002). It must be considered that several data on synaptic numeric density have been collected according to methods used prior to the introduction and the frequent use of the unbiased stereological technique of the disector. Thus, these results cannot be compared with those obtained by the disector; however, they may be useful to estimate ratios as, for instance, synapse-to-neuron, and the conclusions drawn must be referred to the portion of the structure from which samples were obtained.

On the basis of these concepts, a decrease of synaptic number in aging has been documented by several authors in different CNS zones from different animal species and human beings, thus supporting the fact that this alteration is a ubiquitous feature of the aging brain. Reliable support to this assumption is given by relating the number of neurons to the number of synapses estimated in the same CNS zone. The synapse-to-neuron ratio is a parameter independent from artifacts of tissue processing (e.g., shrinkage) or the physiological decrease of the overall volume of a given CNS zone, thus providing reliable information on the real situation of the analyzed tissue area from a morphofunctional standpoint.

In a study conducted in CNS samples from adult, old, and demented (AD) patients at autopsy, the synapse-to-neuron ratio estimated in the cerebellum (glomerular areas in the granular layer) and hippocampus (dentate gyrus supragranular layer) showed different findings

Figure 40.4 Synapse-to-neuron ratio in the cerebellum and hippocampus of adult, old, and demented (AD) patients. No significant difference can be seen in the cerebellar granular layer. This parameter shows a significant (52%) decrease in the hippo-campal dentate gyrus of demented vs. normal old patients of the same age. This result suggests that synaptic loss perse is a prominent alteration of the demented brain in selected CNS areas.

Figure 40.4 Synapse-to-neuron ratio in the cerebellum and hippocampus of adult, old, and demented (AD) patients. No significant difference can be seen in the cerebellar granular layer. This parameter shows a significant (52%) decrease in the hippo-campal dentate gyrus of demented vs. normal old patients of the same age. This result suggests that synaptic loss perse is a prominent alteration of the demented brain in selected CNS areas.

according to the CNS zone and the health condition of the patients (see Figure 40.4). Namely, in the cerebellum there was no significant difference between adult, old, and demented subjects although a reduction of this parameter was clearly evident between the adult group and the other two groups of patients.

In the hippocampal dentate gyrus, the synapse-to-neuron ratio decreased insignificantly between adult and old patients, whereas between adult and AD patients a significant decrease of more than 50% was found. Since in both the areas investigated the number of neurons was almost unchanged with aging, these results suggest that the loss of synapses per se is a prominent and early alteration in physiological brain aging and may represent a sustainable pathological marker in AD.

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Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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