脳における統合的ストレス反応:健康と神経学的障害における細胞型特異的機能

David Ho-Tieng¹, Vijendra Sharma², Nahum Sonenberg³

¹Department of Anesthesia and Faculty of Dental Medicine and Oral Health Sciences, McGill University, Montreal, QC, Canada.

Trends in neurosciences

|September 3, 2025

まとめ

統合ストレス反応 (ISR) ネットワークはタンパク質の合成と細胞の適応を制御する. 細胞特有のISRの役割を理解することは,慢性的なストレスを伴う脳疾患の治療に不可欠です.

科学分野:

分子生物学
神経科学
細胞生物学

背景:

統合ストレス反応 (ISR) は,細胞ストレス中にタンパク質合成を調節する保存経路である.
ISRの活性化は,神経変性および神経発達障害を含む様々な脳病変に関与しています.
異なる脳細胞のタイプは,ストレスに対する異なる感受性と,異なるISR媒介の生理学的反応を示します.

研究の目的:

ISRの細胞型特異的な機能が脳の健康を維持するかを検討する.
脳疾患の文脈におけるISRの役割を検討する.
治療戦略に対する細胞特異のISR活動の影響について議論する.

主な方法:

脳の統合ストレス反応に関する研究の文献レビュー
ストレスとISR活性化に対する細胞タイプ特有の反応の分析
神経疾患におけるISRの関与に関する現在の知識のまとめ

主要な成果:

ISRは神経細胞と膠質細胞のストレスへの適応において重要な役割を果たします.
慢性的なISR活性化は,様々な脳疾患の病原化に寄与する.
細胞の文脈は,脳生理学に対するISR調節の影響に大きな影響を与えます.

結論:

ISRは,健康な脳と病気の脳において,細胞型特異的な機能を示す.
脳の病理に対するISRの治療的ターゲティングは,特定の細胞の脆弱性と反応を考慮する必要があります.
将来の研究は,効果的な治療法を開発するために,細胞特有のISRメカニズムを明確にすることに焦点を当てるべきです.

キーワード:

アストロサイト脳についてメモリマイクログリアニューロンタンパク質合成シナプス可塑性

さらに関連する動画

10:36

Measurements of Physiological Stress Responses in C. Elegans

Published on: May 21, 2020

14.1K

07:13

The Unpredictable Chronic Mild Stress Protocol for Inducing Anhedonia in Mice

Published on: October 24, 2018

17.7K

関連する概念動画

01:24

Physiological Foundation of Stress

157

Stress triggers a coordinated physiological response involving the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis. This dual activation ensures that the body is prepared for both immediate and prolonged stress management. The process begins with the perception of a stressor. This initial phase activates the SNS, leading to the rapid release of adrenaline (epinephrine) from the adrenal glands.
Role of the Sympathetic Nervous System
Adrenaline triggers the...

157

01:21

Stress Response System

198

The stress response system, also known as the fight-or-flight response, is the body's automatic physiological reaction to perceived threats. Hans Selye introduced the concept of General Adaptation Syndrome (GAS) to describe the predictable pattern of changes that occur in response to stress. GAS consists of three sequential stages: alarm, resistance, and exhaustion. This model helps explain how chronic stress can contribute to health problems.
Alarm stage
In the alarm stage, the body's...

198

01:37

Hypothalamic-Pituitary Axis

61.6K

The response to stress—be it physical or psychological, acute or chronic—involves activation of the Hypothalamic-Pituitary-Adrenal (HPA) axis. The HPA axis is part of the neuroendocrine system because it involves both neuronal and hormonal communication. Its function is to regulate homeostatic systems—metabolic, cardiovascular, and immune—providing the necessary means to respond to a stressor.

61.6K

01:13

Functional Brain Systems: Reticular Formation

2.6K

The reticular formation is a complex network of gray and white matter located within the brainstem extending from the medulla to the midbrain.
Within the reticular formation, there are several distinct nuclei that can be classified into three broad categories. The Raphe nuclei are located along the midline of the brainstem. They are primarily known for their role in synthesizing and releasing serotonin, a neurotransmitter involved in regulating mood, appetite, sleep, and circadian rhythms. The...

2.6K

01:25

What is a Nervous System?

Integration of Synaptic Events

2.1K

Synaptic integration mainly includes the summation of graded potentials. Graded potentials, regardless of their type, cause subtle alterations in membrane voltage, resulting in either depolarization or hyperpolarization. These incremental changes, when combined or summed, can propel the neuron toward its threshold. Consider, for example, a membrane experiencing a +15 mV shift, causing it to depolarize from -70 mV to -55 mV. In this scenario, graded potentials govern the membrane's ability to...