Changes in number of synapses and mitochondria in presynaptic terminals in the dentate gyrus following cerebral ischemia and rehabilitation training

Abstract

Damage to the adult brain can result in adaptive plasticity in regions adjacent to the site of the principal insult and that the plastic changes may be modulated by post-injury rehabilitation training. In this study, we examined the effects of rehabilitation training on synaptic morphology in the dentate gyrus following transient global cerebral ischemia and the metabolic correlates of the ultrastructural changes. Forty adult male Wistar rats were included in the study and assigned to either ischemia or sham group. Following ischemic or sham surgery, rats were randomized to either complex environment housing (EC), exercise (EX), or social condition (SC, paired housing) group. Electron microscopy and unbiased stereological methods were used to evaluate synaptic plasticity and the number and size of mitochondria in synaptic axon terminals. Increased number of granule neurons was seen in all ischemic groups and in the sham EC rats. Changes in the number of synapses per neuron in the outer and inner molecular layers of the dentate gyrus parallel those seen in granule neurons. Similarly, ischemia and behavioral experience in EC independently increased the number of synaptic mitochondria in presynaptic terminals in both the outer and inner molecular layers; however, no significant changes were seen in mitochondrial size. These data suggest a link between behavioral training and synaptic plasticity in the region adjacent to the injury and that the likely metabolic correlate of this synaptic plasticity is increased number of mitochondria at synaptic axon terminals.