肌酸可以通过PI3K/AKT/mTOR通路调节GSK-3β来预防ouabain诱导的躁狂行为
Adson Souza-Pereira1, Jozyê Milena da Silva Guerra1, Bruno Henrique Nieswald1
1Biochemistry Graduate Program, Federal University of Pampa, Uruguaiana, RS, Brazil.
Pharmacology, biochemistry, and behavior
|October 12, 2025
概括
肌酸补充剂通过减少大鼠模型中的躁狂行为,显示出对双相情感障碍的承诺. 它通过保持关键酶活性和激活关键细胞通路来起作用,表明作为辅助疗法的潜力.
科学领域:
- 神经科学是一个神经科学.
- 生物化学 生物化学
- 精神病学是一个精神病学.
背景情况:
- 双极性障碍是一种慢性情绪障碍,治疗疗效有限.
- 肌酸具有神经保护性和潜在的情绪稳定性.
- 肌酸对情绪障碍的影响的确切机制尚未完全理解.
研究的目的:
- 在疯狂的小鼠模型中研究肌酸的行为和分子效应.
- 为了阐明神经生物学途径涉及到肌酸的潜在情绪稳定作用.
主要方法:
- 通过使用大脑内室内 (Na+/K+-ATPase抑制剂) 诱导了一种疯狂的小鼠模型.
- 评估了急性口服肌酸 (300 mg/kg) 对行为 (开放场测试) 和海马体分子变化的影响.
- 分析包括Na+/K+-ATPase活性,蛋白质酸化和关键信号通路激活 (PI3K/AKT/mTOR/GSK-3β).
主要成果:
- 在躁狂模型中,肌酸显著降低过度活跃和延迟症状发作.
- 肌酸保留了Na+/K+-ATPase的活性,并降低了它的α-亚单元酸化.
- 肌酸增强了PI3K/AKT/mTOR/p70S6K通路,并抑制了GSK-3β的激活.
- 拉帕米辛 (mTOR抑制剂) 逆转了肌酸的行为效应,证实了途径的参与.
结论:
- 在躁狂模型中,急性摄取肌酸可提供行为和神经化学保护.
- 肌酸的作用通过PI3K/AKT/mTOR通路和Na+/K+-ATPase和GSK-3β的调节进行调节.
- 肌酸显示出作为双相情感障碍辅助治疗策略的潜力.
相关概念视频
cAMP-dependent Protein Kinase Pathways
8.3K
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
8.3K
PI3K/mTOR/AKT Signaling Pathway
5.3K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
5.3K
Mania and Antimanic Drugs: Overview
549
Mania, a psychological condition characterized by elevated mood, increased energy, and reduced sleep need, is part of the bipolar disorder cycle. The exact cause of mania isn't entirely known, but it is thought to be a combination of genetic, environmental, and neurological factors. Bipolar disorder involves alternating manic and depressive episodes. Mood stabilizers like lithium, antipsychotics, and anticonvulsants help manage these episodes. Lithium carbonate is particularly effective as...
549
GPCRs Regulate Adenylyl Cylase Activity
7.3K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
7.3K
Indirect-Acting Cholinergic Agonists: Mechanism of Action
2.5K
Indirect-acting cholinergic agonists work by interacting with an enzyme called acetylcholinesterase (AChE) in the synaptic cleft. They can be reversible or irreversible inhibitors and have different effects on the enzyme.
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex,...
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex,...
2.5K
G-Protein Gated Ion Channels
5.6K
GPCRs are primarily responsible for our sense of smell, taste, and vision. The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory...
Sensory...
5.6K


