メスに偏ったアストロサイトのプライミングは、Aβオリゴマー環境における早期の青斑核脆弱性を形成する

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Updated: Feb 7, 2026

Localization of the Locus Coeruleus in the Mouse Brain

Localization of the Locus Coeruleus in the Mouse Brain

Published on: March 7, 2019

Srishti Kushwaha^1,2, Rupsa Roy Choudhury^1,2, Priyanka Bhat³

¹Centre for Brain Research, Indian Institute of Science, Bangalore, India.

Alzheimer's & dementia : the journal of the Alzheimer's Association

|February 6, 2026

要旨

Introduction:

The locus coeruleus (LC) is an early site of Alzheimer's disease (AD) pathology, yet the role of brainstem astrocytes in early, sex-dependent vulnerability remains unclear.

Methods:

In 2- to 3-month-old APP/PS1 mice, we combined in vivo proton magnetic resonance spectroscopy (MRS) of the brainstem with region-resolved molecular analyses, including quantitative real-time polymerase chain reaction, amyloid beta 42 (Aβ42) oligomers enzyme-linked immunosorbent assay, lactate assay, immunohistochemistry, immunoblotting, astrocyte isolation, and 3D structural assessment. Environmental enrichment (EE) served as a non-pharmacologic intervention.

Results:

Females exhibited higher brainstem Aβ42 oligomers and an astrocyte-weighted MRS profile. Pontine glial fibrillary acidic protein (GFAP), complement component 3, and nuclear factor kappa-light-chain-enhancer of activated B cells were selectively upregulated without pan-reactive astrocytic and microglial markers. LC-restricted GFAP elevation occurred without changes in astrocyte counts or morphology, indicating a "primed" state. Females also showed higher lactate levels, increased monocarboxylate transporter 2 expression, and elevations in selected oxidative phosphorylation-associated transcripts, and reduced astrocytic alpha 2A-adrenergic receptor expression. EE normalized noradrenergic and pontine astrocytic changes.

Discussion:

Female-biased, LC-centric astrocytic priming emerges early in this amyloid-driven model and is modifiable.

キーワード:

α2Aアドレナリン受容体アミロイドβオリゴマーアストロサイト活性化環境エンリッチメント青斑核ノルアドレナリン作動性シグナル伝達ノルエピネフリントランスポーター前臨床アルツハイマー病プロトン磁気共鳴分光法性差

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Assessing Pupil-linked Changes in Locus Coeruleus-mediated Arousal Elicited by Trigeminal Stimulation

Assessing Pupil-linked Changes in Locus Coeruleus-mediated Arousal Elicited by Trigeminal Stimulation

Published on: November 26, 2019

Analyzing the Size, Shape, and Directionality of Networks of Coupled Astrocytes

Analyzing the Size, Shape, and Directionality of Networks of Coupled Astrocytes

Published on: October 4, 2018

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