Exercise-Induced Synaptogenesis in the Hippocampus Is Dependent on UCP2-Regulated Mitochondrial Adaptation

Abstract

Mitochondria are essential organelles in neurons providing appropriate energetic needs to maintain resting and action potentials as well as to modulate synaptic plasticity. Although neuronal events underlie various behavioral events, the behavior itself, such as voluntary exercise, feeds back to affect neuronal morphology and function as well as glial morphology and function. The hippocampal formation is a main site of synaptic plasticity induced by voluntary exercise. Here we show that voluntary exercise induces uncoupling protein 2 (UCP2) mRNA expression and mitochondrial oxygen consumption in coupled as well as uncoupled respiratory states in the hippocampus. These changes in mitochondrial metabolism coincided with an increase in mitochondrial number and dendritic spine synapses in granule cells of the dentate gyrus and the stratum radiatum of the CA1 region and were dependent on UCP2 expression, because in UCP2 knock-out mice such changes were not observed. Together, these observations reveal that a mitochondrial mechanism related to UCP2 function is essential for appropriate bioenergetic adaptation of neurons to increased neuronal activity and synaptic plasticity in response to exercise.

Sigma-1 receptors regulate hippocampal dendritic spine formation via a free radical-sensitive mechanism involving Rac1·GTP pathway

“…ER and mitochondria have been reported to participate in dendritic spine formation (35)(36)(37)(38)(39). Our results provide additional insights on how these two intracellular organelles may participate in dendritic spine formation in a unique fashion.…”

“…Contrary to the notion that ER does so by regulating Ca 2ϩ efflux via ryanodine or IP 3 receptors on the ER membrane (35-37), our results indicate that the ER might regulate dendritic spine formation in hippocampal neurons via a free radical-related mechanism that might not involve Ca 2ϩ signaling. Mitochondria supply energy for cells and are important in neural development (38,39). Our results indicate that mitochondria might participate in dendritic formation via a TIAM1-Rac1⅐GTP signaling pathway.…”

Mechanisms of Retinal Ganglion Cell Injury in Aging and Glaucoma

“…Another means of enhancing mitochondrial function is exercise. Physical activity is a potent stimulator of mitochondrial biogenesis in muscle, heart and brain, which leads to enhanced oxidative phosphorylation activity and a corresponding increase in oxygen consumption and ATP synthesis [57][58][59] . Although the modulating effects of ex ercise on retinal mitochondria are yet to be shown, preliminary evidence suggests that vigorous physical activity may reduce glaucoma risk [60] .…”

Enhanced neuroprotective effects for co-administration of g-csf with simvastatin on intracerebral hemorrhage in rats

“…The results showed that combination therapy group with G-CSF and simvastatin was superior to either one alone in increasing synaptic vesicles density in the boundary zone around the hematoma. It appears that synaptic vesicles play critical role in regulating synaptic reorganization (6). Besides, the combined treatment group had significant neurological improvement from 1 week post-ICH onward.…”