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Session XII : Cell death <strong>and</strong> neurodegenerative diseases Poster XII, 2<br />

Age-related decline of synaptic turnover as an early event in neurodegeneration<br />

Carlo Bertoni-Freddari, Patrizia Fattoretti, Belinda Giorgetti, Yessica Grossi, Marta<br />

Balietti, Tiziana Casoli, Giuseppina Di Stefano, *Gemma Perretta<br />

Neurobiology of Aging Laboratory, INRCA Research Department, Via Birarelli 8,<br />

60121 Ancona, Italy Email: c.bertoni@inrca.it <strong>and</strong> *Istituto di Neurobiologia e<br />

Medicina Molecolare-CNR, S.p Anguillarese km 1.3, 00060 Roma, Italy<br />

The changes of synaptic ultrastructure in the frontal (FC) <strong>and</strong> temporal (TC) cortex were<br />

investigated in adult <strong>and</strong> aged monkeys (Macaca fascicularis), by means of quantitative<br />

morphometry, in order to assess the potential role of age-related synaptic deterioration in<br />

neurodegeneration. The average synaptic size (S), the synaptic numeric density (Nv: number<br />

of synapses/cubic micron of tissue), the synaptic surface density (Sv: overall area of synaptic<br />

junctional zones/cubic micron of tissue) <strong>and</strong> the number of synapses/neuron (Syn/Neur) were<br />

semiautomatically measured by a computer-assisted image analysis system. The results of FC<br />

evaluation revealed no significant differences of Nv <strong>and</strong> Sv between adult <strong>and</strong> old monkeys,<br />

while S was significantly increased in the aged animals. In TC, Sv did not show changes due<br />

to age, while Nv was significantly decreased <strong>and</strong> S was significantly increased in aged<br />

monkeys. The fraction (%) of perforated junctions was similar in FC <strong>and</strong> TC of the adult<br />

animals, while it was decreased by 22.6% in TC vs. FC in the old monkeys. A percent<br />

distribution of S showed that the fraction of enlarged synapses (>0.20 square micron) was<br />

higher in TC than in FC regardless of the age of the animals (21.3% vs.16.9% in adult <strong>and</strong><br />

33.9% vs. 26.0% in aged monkeys, respectively). The comparison between data from adult<br />

<strong>and</strong> old TC revealed that the increase was markedly higher in aged monkeys (i.e. 33.9% vs.<br />

21.3%). In these animals, Syn/Neur was significantly decreased by 14.1% in TC, whereas it<br />

was not significantly reduced in FC (- 4.4%). Sv, Nv, S <strong>and</strong> Syn/Neur are morphometric<br />

parameters currently adopted to estimate the ongoing rearrangements of synaptic<br />

ultrastructure to react to environmental stimuli. Our findings provide evidence of an agerelated<br />

decline of synaptic plasticity in the brain of aged monkeys that is significant in TC.<br />

According to current literature data on synaptic structural dynamics, this decay might<br />

represent an early <strong>and</strong> subtle alteration able to trigger the development of senile plaques <strong>and</strong><br />

neurodegenerative events.<br />

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