2007 Fiscal Year Final Research Report Summary
The role of adult hippocampal neurogenesis underlying stress vulnerability
| Project/Area Number |
18591269
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | Hokkaido University |
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Principal Investigator |
NAKAGAWA Shin Hokkaido University, Grad. School of Med., Assistant Professor (60360905)
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| Co-Investigator(Kenkyū-buntansha) |
INOUE Takeshi Hokkaido University, Grad. School of Med., Lec. (70250438)
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| Project Period (FY) |
2006 – 2007
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| Keywords | antidepressant / stem cell / hippocampus / cortisol / neuronal cell culture / mood stabilizer / neurotrophic factor / MRI |
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| Research Abstract |
1) The effect of stabilizers, antidepressants and monoamines to neural stem / progenitor cells derived from adult rat dentate gyrus.
To evaluate the direct effect of stabilizers, antidepressants and monoamines to neurogenesis in the adult hippocampus, we established a culture system of neural stem / progenitor cells derived from adult rat dentate gyrus. Glucocorticoid of which serum level is increased under stress condition decreased a proliferation rate of the cells. On the contrary, both lithium and valproic acid recovered this glucocorticoid's effect. The β-catenin / TCF system was shown to play an important role in these stabilizer's action. On the other hand, antidepressants including SSRI and SNRI did not have any effects. Noradrenaline, but not serotonin, increased the cells thorough β 2 receptor with dose dependent manner. These results suggested antidepressants increased a hippocampal neurogenesis in various ways.
2) The relationship between the activity of HPA axis and hippocam
… More
pal volume.
There is compelling evidence for an important role of HPA axis abnormalities in the pathophysiology of mood disorders. Moreover, raised level of cortisol has been shown to produce the neuronal dysfunction of hippocampus with shrunken cell bodies in CA3 and decreased neurogenesis in dentate gyrus. In this study we investigated the relationship between the HPA abnormalities assessed with combined dexamethasone (DEX) / corticotropine-releasing hormone (CRH) test and hippocampal volume measured by manual segmentation on MRI in depressive patients. Significant enhanced pituitary-adrenocortical response to the DEX/CRH test were observed in depressive patients compared with controls. Moreover, hippocampal volume of patients was significantly decreased. The reduction was greater in 'nonsuppressor' who showed 〓 5μg/dl of cortisol concentration on any time points of combined DEX/CRH test compared with 'suppressors'. These results suggest that HPA axis abnormalities might be associated to the reduction of hippocampal volume in subjects suffered from mood disorder. Less
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