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.
SourceAvailable from: Joop D LefrandtAtherosclerosis 05/2011; 216(1):249-249. DOI:10.1016/j.atherosclerosis.2011.02.042 · 3.97 Impact Factor
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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 · 2.85 Impact Factor
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ABSTRACT: Caloric restriction (CR) is a reduction of total caloric intake without a decrease in micronutrients or a disproportionate reduction of any one dietary component. While CR attenuates age-related cognitive deficits in tasks of hippocampal-dependent memory, the cellular mechanisms by which CR improves this cognitive decline are poorly understood. Previously, we have reported age-related decreases in key synaptic proteins in the CA3 region of the hippocampus that are stabilized by lifelong CR. In the present study, we examined possible age-related changes in the functional microcircuitry of the synapses in the stratum lacunosum-molecular (SL-M) of the CA3 region of the hippocampus, and whether lifelong CR might prevent these age-related alterations. We used serial electron microscopy to reconstruct and classify SL-M synapses and their postsynaptic spines. We analyzed synapse number and size as well as spine surface area and volume in young (10 months) and old (29 months) ad libitum fed rats and in old rats that were calorically restricted from 4 months of age. We limited our analysis to SL-M because previous work demonstrated age-related decreases in synaptophysin confined to this specific layer and region of the hippocampus. The results revealed an age-related decrease in macular axo-spinous synapses that was not reversed by CR that occurred in the absence of changes in the size of synapses or spines. Thus, the benefits of CR for CA3 function and synaptic plasticity may involve other biological effects including the stabilization of synaptic proteins levels in the face of age-related synapse loss.Neuroscience 12/2010; 171(2):373-82. DOI:10.1016/j.neuroscience.2010.09.022 · 3.33 Impact Factor