Research reportEffects of soft-diet feeding on synaptic density in the hippocampus and parietal cortex of senescence-accelerated mice
Introduction
Masticatory movements originate through co-ordinated activities of the masticatory muscles. Such movements produce various types of stimulation to mechanoreceptors in the oro-facial regions. Sensory afferents from these mechanoreceptors may exert extensive influences on the development and excitability of the central nervous system. During voluntary teeth clenching, a volley of afferent impulses from the periodontal mechanoreceptors increases the amplitude of the soleus Hoffman’s reflex in proportion to the strength of the clenching [28]. These afferent impulses may also be important during development. In rats fed only a liquid diet after weaning, the contraction timing of the jaw and tongue muscles can not be programmed for chewing, but only for lapping or licking, even at 50 days after birth [19]. This suggests that the amount of sensory input had been insufficient to facilitate development of the central pattern generator in order to masticate. Moreover, sensory inputs from oro-facial regions have been shown to elicit psychosomatic effects. Chewing a marketed gum for 3 min significantly increased the mean frequency of the alpha band of the electroencephalogram recording compared with that in the control recording, reflecting arousal responses by the chewing [25]. Despite these results, little attention has been given in the literature to the influences of masticatory activity on learning and memory functions. It has been reported that the acquisition of the spatial memory in aged rats [14] and mice [31] is impaired by extracting or cutting of their molar teeth at young age, and that neuronal density in the CA1 field of the hippocampal formation is lower in the toothless mice compared with controls [31]. However, the specific morphological changes underlying the behavioral impairment remain to be elucidated.
Morphological quantification of synaptic terminals can present valuable information about the status of brain neural networks. Indeed, synaptic density in the hippocampal formation is responsible for the severity of cognitive impairment in aged animals [4], [7], [27] and in Alzheimer’s disease [1], [24]. Likewise, synaptic density in the parietal cortex correlates with maze performances of rats [41]. For the investigation of the synaptic profile distribution in the brain, synaptophysin immunoreactivity has been widely used as a suitable marker [1], [7], [17], [24], [41] in addition to electron microscopy [9], [10]. Synaptophysin is a calcium-binding glycoprotein specifically located in the membrane of presynaptic vesicles [40]. To determine whether or not working memory is impaired by feeding with a powdered diet, the senescence-accelerated mouse (SAM) model of accelerated aging is useful, because learning and cognitive abilities significantly differ among its substrains [36]. SAMP8, one of the strains prone to accelerated senescence, exhibits age-related learning and memory disturbances in passive-avoidance and open-field tests compared with SAMR1, a senescence-resistant strain. These differences are apparent after 4 months of age [29]. The present study initially examined the respective effects of soft-diet feeding and aging on the synaptophysin content in the cerebral cortex of the SAMR1 and SAMP8 mice by radioimmunoassay. Regional variations of the synaptophysin expression at a typical age were examined in the hippocampus and parietal II region of the neocortex (secondary somatosensory cortex) by immunohistochemistry. Then numerical density of synapses was assessed in these regions by electron microscopy. We also tested the spatial memory of the animals using an eight-arm radial maze.
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Animals
SAMR1 and SAMP8 mice were originally provided as breeding pairs by Dr Masanori Hosokawa (Department of Senescence Biology, Chest Disease Research Institute, Kyoto University, Kyoto, Japan) and bred in the laboratory animal facility of our institution. Male pups of both strains were weaned at 3 weeks after birth and housed in groups of five in standard plastic cages (30×20×14 cm) with wire mesh lids and a bedding of wood shavings. The cages were placed in an air-conditioned room (23±1°C) with a
Synaptophysin content in cerebral cortex
We evaluated the synaptophysin content in the entire cerebral cortex of the R1-H, P8-H, R1-S and P8-S mice by radioimmunoassay (Fig. 1). The level of synaptophysin radioactivity was lower in P8-H than in R1-H mice at all ages investigated. Two-way ANOVA on the radioactivity levels of the R1-H and P8-H groups revealed significant effects of strain (F1,96=455.585, P<0.001) and age (F5,96=21.205, P<0.001), and significant interaction (F5,96=11.877, P<0.001). The amount of R1-H radioactivity
Discussion
To our knowledge, this is the first study on synaptogenesis in the brain of the senescence-accelerated mouse. Radioimmunoassay revealed that the synaptophysin content in the cerebral cortex of R1-H mice peaked at 3 months of age then remained at almost constant levels until 12 months of age (Fig. 1). This result was in agreement with the findings of a study of synaptophysin expression in the mouse cerebrum measured by immunoblotting [17]. Synaptic formation in the mouse cerebral cortex was
Acknowledgements
This work was supported by an Oral Health Science Center Grant from Tokyo Dental College (961D02).
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