Caloric restricted male rats demonstrate fewer synapses in layer 2 of sensorimotor cortex

Department of Neurobiology and Anatomy, Medical Center Boulevard, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1010, USA.
Brain Research (Impact Factor: 2.84). 04/2002; 931(1):32-40. DOI: 10.1016/S0006-8993(02)02249-7
Source: PubMed


Previous studies have demonstrated an age-related decline in the density of presumptive inhibitory synapses in layer 2 of rat sensorimotor cortex [J. Comp. Neurol. 439(1) (2001) 65]. Caloric restriction has been shown to ameliorate age-related deterioration in a variety of systems and to extend life span. The present study tested the hypothesis that caloric restriction would prevent the previously reported age-related synaptic decline. Accordingly, synaptic density in layer 2 of sensorimotor cortex was compared between 29-month-old male rats fed ad libitum and 29-month-old male rats that were caloric restricted (60% of ad libitum calories) from 4 months of age. In serial electron micrographs, the physical disector was used to determine the numerical density of presumptive excitatory and inhibitory synapses (those containing round or nonround vesicles, respectively) as well as that of neurons. Not only was the previously reported age-related decline in numerical density of presumptive inhibitory synapses not ameliorated by caloric restriction, the numerical density was significantly lower in caloric restricted than in ad libitum fed rats for total as well as for presumptive excitatory and inhibitory synapses. Analysis further revealed no difference in the numerical density of neurons in this region. Relating synapse density to neuron density as the ratio of synapses to neuron also demonstrated significantly fewer synapses per neuron in caloric restricted than in ad libitum fed old rats. Finally, synapse length was significantly less in caloric restricted rats. These results suggest that not only does caloric restriction fail to prevent the age-related decline in presumptive inhibitory synapses, it results in fewer presumptive excitatory synapses as well.

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    • "CR acts via IGF-1 to enhance plasticity of the brain (Mattson et al., 2002), and delays age-related neuronal loss in the enteric nervous system (Cowen et al., 2002; Thrasivoulou et al., 2006). However, a decrease of synaptic connections under CR was also reported (Shi et al., 2002). "
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    • "Sixty-four rats were in the cohort used for biochemical analysis and seventy-two rats in the behavioral cohort. The F344xBN hybrid is a widely-used model for studies of age and CR (Mayhew et al., 1998; Shi et al., 2002; Ramsey et al., 2004; Newton et al., 2005; Shi et al., 2007) and demonstrates CRmediated protection of learning and memory after middle age (Markowska and Savonenko, 2002). Young (10-12 months), middle-aged (18-20 months), and old (29-32 months) rats were obtained from the NIA Caloric Restriction Colony (Harlan Industries) and were maintained in our facility on a 12-hour light/dark cycle for two months prior to sacrifice. "
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    • "Each physical disector consisted of a pair of photomicrographs (38000; Zeiss 10-C transmission electron microscope) from serial thin sections through the stratum radiatum of CA1. Pairs of serial section were chosen in a systemically random fashion as described previously (Shi et al., 2002) and consistent with the requirement for stereological analysis (Geinisman et al., 1996). Thin and semithin sections were from alternating sectors in individual blocks in order to provide sampling of synaptic profiles and neurons through coincident anatomical space. "
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