動物実験であるが、血液脳関門と脳機能の低下をブリッジするのがPAMPだろうと考えられる。
Article
Published: 03 July 2019
Single-cell analysis reveals T cell infiltration in old neurogenic niches
Ben W. Dulken, Matthew T. Buckley, […]Anne Brunet
Nature volume 571, pages205–210 (2019) | Download Citation
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Abstract
The mammalian brain contains neurogenic niches that comprise neural stem cells and other cell types. Neurogenic niches become less functional with age, but how they change during ageing remains unclear. Here we perform single-cell RNA sequencing of young and old neurogenic niches in mice. The analysis of 14,685 single-cell transcriptomes reveals a decrease in activated neural stem cells, changes in endothelial cells and microglia, and an infiltration of T cells in old neurogenic niches. T cells in old brains are clonally expanded and are generally distinct from those in old blood, which suggests that they may experience specific antigens. T cells in old brains also express interferon-γ, and the subset of neural stem cells that has a high interferon response shows decreased proliferation in vivo. We find that T cells can inhibit the proliferation of neural stem cells in co-cultures and in vivo, in part by secreting interferon-γ. Our study reveals an interaction between T cells and neural stem cells in old brains, opening potential avenues through which to counteract age-related decline in brain function.
脳内炎症は既に慢性披露症候群と関連するという研究成果が出ているが、認知機能の加齢現象と関係付けられるだろう。BBBを開く食品や微生物の産物が認知低下を招いている。脳はエネルギー喰いであり余剰エネルギーなしにホモサピエンスの進化は考えられない。
九州大学大学院農学研究院/五感応用デバイス研究開発センターの松井利郎教授の研究グループは、福岡大学薬学部道具伸也准教授やブルカージャパン（株）等との共同研究により、ペプチドが血液脳関門を透過し、脳組織に蓄積することを、マウスを用いた灌流試験によって世界で初めて明らかにしました。これまで、グルコースやアミノ酸などの栄養成分は血液脳関門を透過するものの、その他の食品成分や異物は厳格にブロックされ、血液脳関門は通過しないとされてきました。それに対して、本研究グループはアミノ酸が２つ結合したジペプチドが血液脳関門を通ることを実証し、さらにマウス脳の海馬、視床下部や小脳周辺に蓄積することを明らかにしました。これらの脳器官は記憶や行動に関わっていることから、ペプチド摂取による脳機能改善作用が大いに期待される成果といえます。なお、本研究は日本学術振興会科学研究費（17K19912）の支援を受けました。
本成果は、2019年4月8日（月）18時（日本時間）に英科学誌「Scientific Reports」誌にオンライン掲載されました。
そして自殺に関係するPAMPとDAMP
Innate immunity in the postmortem brain of depressed and suicide subjects: Role of Toll-like receptors
Author links open overlay panelGhanshyam N.PandeyHooriyah S.RizaviRunaBhaumikXinguoRen
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https://doi.org/10.1016/j.bbi.2018.09.024Get rights and content
Highlights
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The expression of several TLRs is increased in prefrontal cortex of depressed suicide subjects.
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There is a dissociation in gene and protein expression of several TLRs in depressed suicide subjects.
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These findings suggest an abnormality of innate immunity in depression and suicide.
Abstract
Abnormalities of Toll-like receptors (TLRs) have been implicated in the pathophysiology of depression and suicide. Interactions of TLRs with pathogen-associated molecular patterns (PAMP) and damage-associated molecular patterns (DAMP) initiate signaling through myeloid differentiation primary response-88 (MyD88) and produce cytokines through the activation of the transcription factor nuclear factor kappa beta (NF-kB). We have earlier shown an increase in the protein and mRNA expression of TLR3 and TLR4 in the prefrontal cortex (PFC) of depressed suicide (DS) subjects compared with normal control (NC) subjects. To examine if other TLRs are altered in postmortem brain, we have now determined the protein and mRNA expression of other TLRs (TLR1, TLR2, TLR5, TLR6, TLR7, TLR8, TLR9 and TLR10) in the PFC of DS, depressed non-suicide (DNS), non-depressed suicide (NDS) and NC subjects. We determined the protein expression by Western blot and mRNA expression levels by real-time PCR (qPCR) in the PFC of 24 NC, 24 DS, 12 DNS and 11 NDS subjects. Combined with our previous study of TLR3 and TLR4, we found that the protein expression of TLR2, TLR3, TLR4, TLR6 and TLR10, and mRNA expression of TLR2 and TLR3 was significantly increased in the DS group compared with NC group. This study demonstrated that certain specific TLRs are altered in DS subjects, and hence those TLRs may be appropriate targets for the development of therapeutic agents for the treatment of suicidal behavior.
