Caloric restricted male rats demonstrate fewer synapses in layer 2 of sensorimotor cortex
ABSTRACT 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). "
ABSTRACT: Spiral ganglion neurons (SGNs) are the relay station for auditory information between hair cells and central nervous system. Age-related decline of auditory function due to SGN loss can not be ameliorated by hearing aids or cochlear implants. Recent findings clearly indicate that survival of SGNs during aging depends on genetic and environmental interactions, which can be demonstrated at the systemic, tissue, cellular, and molecular levels. At the systemic level, both insulin/insulin-like growth factor-1 and lipophilic/steroid hormone pathways influence SGN survival during aging. At the level of organ of the Corti, it is difficult to determine whether age-related SGN loss is primary or secondary degeneration. However, a late stage of SGN degeneration may be independent of age-related loss of hair cells. At the cellular and molecular level, several pathways, particularly free radical and calcium signaling pathways, can influence age-related SGN loss, and further studies should determine how these pathways contribute to SGN loss, such as whether they directly or indirectly act on SGNs. With the advancement of recent genetic and pharmacologic tools, we should not only understand how SGNs die during aging, but also find ways to delay this loss.Hearing research 10/2009; 264(1-2):93-7. DOI:10.1016/j.heares.2009.10.009 · 2.97 Impact Factor
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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. "
ABSTRACT: Caloric restriction (CR) is a daily reduction of total caloric intake without a decrease in micronutrients or disproportionate reduction of any one dietary component. CR can increase lifespan reliably in a wide range of species and appears to counteract some aspects of the aging process throughout the body. The effects on the brain are less clear, but moderate CR seems to attenuate age-related cognitive decline. Thus, we determined the effects of age and CR on key synaptic proteins in the CA3 region of the hippocampus and whether these changes were correlated with differences in behavior on a hippocampal-dependent learning and memory task. We observed an overall, age-related decline in the NR1, N2A and N2B subunits of the N-methyl-d-aspartate (NMDA)-type and the GluR1 and GluR2 subunits of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA)-type ionotropic glutamate receptors. Interestingly, we found that CR initially lowers the glutamate receptor subunit levels as compared to young AL animals, and then stabilizes the levels across lifespan. Synaptophysin, a presynaptic vesicle protein, showed a similar pattern. We also found that both CR and ad libitum (AL) fed animals exhibited age-related cognitive decline on the Morris water maze task. However, AL animals declined between young and middle age, and between middle age and old, whereas CR rats only declined between young and middle age. Thus, the decrease in key synaptic proteins in CA3 and cognitive decline occurring across lifespan are stabilized by CR. This age-related decrease and CR-induced stabilization are likely to affect CA3 synaptic plasticity and, as a result, hippocampal function.Experimental Neurology 06/2008; 211(1):141-9. DOI:10.1016/j.expneurol.2008.01.016 · 4.70 Impact Factor
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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. "
ABSTRACT: Aging-related impairments of learning and memory can be ameliorated by 28 days of intracerebroventricular (icv) infusion of insulin-like growth factor-1 (IGF-1) in old rats. The present study investigated whether there is an aging-related synaptic decline in the stratum radiatum of hippocampal CA1 and whether IGF-1 can ameliorate that decline. Five young (4 months), five middle-aged (18 months) and five old (29 months) Fischer 344xBrown Norway rats received saline infusion; five old (29 months) rats received IGF-1 infusion for 28 days preceding sacrifice. Pyramidal neurons, total synaptic profiles as well as synaptic profiles in multiple spine bouton (MSB) complexes in CA1 were quantified stereologically with the physical disector technique and the postsynaptic density (PSD) length was determined as well. The results indicated a decrease of total synapses between middle and old age but a maintenance of PSD length and MSB synapses throughout life. IGF-1 infusion in old rats did not reverse the aging-related decline in total synapses but did increase PSD length and the number of MSB synapses. These changes in synaptic configurations are morphological correlates of enhanced synaptic efficacy. Thus, aging and IGF-1 affect different, but complementary, aspects of synapses in hippocampal CA1.Cerebral Cortex 06/2005; 15(5):571-7. DOI:10.1093/cercor/bhh158 · 8.67 Impact Factor