2021 Fiscal Year Final Research Report
Unraveling the mechanism of anxiety and depression by early-life stress: Analysis of stress information processing circuits
| Project/Area Number |
20K16486
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 51030:Pathophysiologic neuroscience-related
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| Research Institution | University of Toyama |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2022-03-31
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| Keywords | 外側手綱核 / 幼少期ストレス / パルブアルブミン陽性神経細胞 / Zif268/Egr1陽性神経細胞 / グルタミン酸作動性 / GABA作動性 / 不安 / うつ |
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| Outline of Final Research Achievements |
In mice, early-life stress led to late effects in adulthood: hyperactivity and fewer parvalbumin positive neurons (PV neurons) in the lateral habenula (LHb), and anxiety/depression. Specific alterations in the LHb induced by early life stress are likely to be involved in behavioral changes and are thought to be one of the brain mechanisms by which anxiety and depression develop, but their causal relationship is unclear. We revealed that 70% of the PV neurons of LHb is the vesicular glutamate transporter 2 positive. PV neurons in the LHb is thought to be related to the behavioral regulation as an excitatory glutamatergic neuron.
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| Free Research Field |
神経科学
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| Academic Significance and Societal Importance of the Research Achievements |
これまで，「PV陽性神経細胞はGABA作動性で，局所回路を抑制する介在神経細胞である」という大脳皮質における研究結果に基づく定説があったが，それを覆す結果が得られた．LHbのPV陽性神経細胞は大脳皮質とは異なる機能を有している可能性が高い．
LHbのPV陽性神経細胞とZif268/Egr1陽性神経細胞は，グルタミン酸作動性の興奮性神経細胞として，幼少期ストレスによって生じる成長後の不安とうつに関与していると考えられる．本研究により，幼少期ストレスによって生じる不安とうつのメカニズムの一端が明らかになった．
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