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Background Pessimistic thinking about the future is one of the cardinal symptoms of major depressive disorder (MDD) and is an important domain of cognitive functioning associated with hopelessness. Neuroimaging studies have shown that the frontopolar cortex (Brodmann area [BA] 10) is involved in thinking about the future and demonstrated that patients with MDD have dysfunctions in BA10. However, the relationship between pessimistic thinking about the future and brain activity is unclear. Hence, we aimed to compare brain activity during future-thinking between patients with MDD and healthy individuals. Methods We assessed 23 patients with current MDD and 23 healthy individuals. Participants were instructed to imagine the future or to recall the past using the future-thinking paradigm with four distinct temporal conditions (distant future, near future, distant past, and near past) during functional MRI. Resting-state functional MRI was also performed to explore the functional connectivity of BA10. Results Compared with healthy individuals, patients with MDD had greater negative thinking about the distant future and exhibited increased activation in the medial BA10 when imagining the distant future, following small-volume correction focusing on the frontopolar a priori region of interest (family-wise error correction p < 0.05). Increased positive functional correlation between the right BA10 seed region and the posterior cingulate cortex was also observed. Conclusion Patients with MDD who show greater pessimistic thinking about the distant future demonstrate increased activation in the frontopolar cortex. These findings are consistent with the hypothesis that frontopolar cortical dysfunction plays a key role in the hopelessness that manifests in patients with MDD.

Summary:We examined the effect of occlusal disharmony in senescence-accelerated (SAMP8) mice on plasma corticosterone levels, spatial learning in the water maze, fos induction, hippocampal neuron number, expression of glucocorticoid receptors (GR) and glucocorticoid receptor messenger ribonucleic acid (GRmRNA) in hippocampus and inhibitor of glucocorticoid (metyrapone).Bite-raised aged mice had significantly greater plasma corticosterone levels than age-matched control mice as well as impaired spatial memory and decreased Fos induction and a number of neurons in hippocampus. GR and GRmRNA expressions were significantly decreased in aged bite-raised mice compared with age-matched control mice. Pretreatment with metyrapone inhibited not only the bite-raised induced increase in plasma corticosterone levels, but also the reduction in the number of hippocampal neurons and impaired spatial learning.These datas suggest that the bite-raised condition may enhance the aging process in hippocampus, thereby leading to impairment of spatial memory by stress.

We evaluated whether long-term tooth loss induces functional and morphologic changes in the hippocampus in senescence-accelerated mice (SAMP8) maintained until old age after tooth extraction shortly after tooth eruption. First, to examine whether early tooth loss acts as a stressor, plasma concentration was measured as an index of stress. Plasma corticosterone concentration was significantly higher in old or mature mice with tooth extraction than in the age-matched controls. Plasma corticosterone concentration did not differ between the young tooth extraction and their age-matched control groups. Next, hippocampal function was assessed by evaluating spatial memory performance in the Morris water maze. In the Morris water maze learning and memory trials was significantly slower in the mature or old tooth extraction groups compared with the age-matched controls. There was no significant difference, however, between the young tooth extraction and control groups. Finally, hippocampal neuronal morphology was assessed by counting Nisslstained cells. The number of hippocampal neurons was significantly reduced in the CA3 region in the mature and old tooth extraction groups compared with their age-matched controls, but there was no significant difference in the CA1-region or dentate gyrus between the mature or old tooth extraction groups and their age-matched controls. In young mice, there was no significant difference in the number of neurons in CA1, CA3, or dentate gyrus region between the tooth extraction and control groups. The findings indicated that tooth extraction after tooth eruption enhances the effects of aging on the hippocampus in mice. exposed to chronic stress 7) , tooth loss is thought to act as a chronic stressor. Chronic stress impairs spatial memory 8) , and leads to a decrease in neurons 9) , an increase in glial fibrillary acidic protein-positive cells 10) , a decrease in acetylcholine release in the higher centers of the brain 11) , particularly the hippocampus, and a decrease in Fos-positive cells in areas of the hippocampus considered important for learning 12). In all of these studies, however, the teeth were extracted at young, mature, and old ages and soon induces functional and morphologic changes. In the present study, we extracted the teeth soon after eruption, maintained the animals until maturation

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