Selective dysfunction of fast-spiking inhibitory interneurons and disruption of perineuronal nets in a tauopathy mouse model

被引：10

作者：

Kudo, Takehiro ^{[1
,2
,4
]}

Takuwa, Hiroyuki ^{[2
,3
]}

Takahashi, Manami ^{[2
,3
]}

Urushihata, Takuya ^{[2
]}

Shimojo, Masafumi ^{[2
]}

Sampei, Kazuaki ^{[1
]}

Yamanaka, Mitsugu ^{[1
]}

Tomita, Yutaka ^{[5
]}

Sahara, Naruhiko ^{[2
]}

Suhara, Tetsuya ^{[2
,3
]}

Higuchi, Makoto ^{[2
]}

机构：

[1] Sumitomo Pharm Co Ltd, Osaka, Japan

[2] Natl Inst Quantum Sci & Technol, Inst Quantum Med Sci, Dept Funct Brain Imaging, Chiba 2638555, Japan

[3] Natl Inst Quantum Sci & Technol, Inst Quantum Life Sci, Dept Neuromapping & Neuromodulat Grp, Chiba 2638555, Japan

[4] Tohoku Univ, Collaborat Chairs Quantum Life Sci and Mol Imaging, Sendai, Japan

[5] Keio Univ, Dept Neurol, Sch Med, Tokyo, Japan

来源：

ISCIENCE | 2023年 / 26卷 / 04期

关键词：

GATED SODIUM-CHANNELS; BETA-SECRETASE; ALZHEIMERS-DISEASE; NEURONAL-ACTIVITY; CATHEPSIN-S; PYRAMIDAL NEURONS; EXPRESSION; IMPAIRMENT; ACTIVATION; NEOCORTEX;

D O I：

10.1016/j.isci.2023.106342

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

In Alzheimer's disease (AD), network hyperexcitability is frequently observed and associated with subsequent cognitive impairment. Dysfunction of inhibitory interneurons (INs) is thought to be one of the key biological mechanisms of hype -excitability. However, it is still unknown how INs are functionally affected in tau pathology, which is a major pathology in AD. To clarify this, we evaluated the neuronal activity of cortical INs in 6-month-old rTg4510 mice, a model of tauop-athy. Calcium imaging with mDlx enhancer-driven labeling revealed that neuronal activity in INs was decreased in rTg4510 mice. In the patch clamp recording, the firing properties of fast-spiking INs were altered so as to reduce their activity in rTg4510 mice. In parallel with microglial activation, perineuronal nets around par-valbumin-positive INs were partially disrupted in rTg4510 mice. Taken together, our data indicate that the excitability of cortical fast-spiking INs is decreased, possibly because of the disruption of perineuronal nets.

引用

页数：23

共 87 条

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