Related Experiment Video
Updated: Feb 6, 2026
Minimally Invasive Endoscopic Intracerebral Hemorrhage Evacuation
Published on: October 15, 2021
Stably maintained microtubules protect dopamine neurons and alleviate depression-like behavior after intracerebral
Yang Yang1, Kaiyuan Zhang1, Jun Zhong1
1Department of Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 29 Gaotanyan Street, 400038, China.
Abstract:
Mesolimbic dopamine (DA) system lesion plays a key role in the pathophysiology of depression, and our previous study demonstrated that reduced microtubule (MT) stability aggravated nigrostriatal pathway impairment after intracerebral hemorrhage (ICH). This study aimed to further investigate the occurrence regularity of depression-like behavior after ICH and determine whether maintaining MT stabilization could protect DA neurons in ventral tegmental area (VTA) and alleviate depression-like behavior after ICH. An intrastriatal injection of 20 μl of autologous blood or MT depolymerization reagent nocodazole (Noco) was used to mimic the pathology of ICH model in mice. The concentration of DA, number of DA neurons and acetylated α-tubulin (a marker for stable MT) in VTA were checked, and depression-related behavior tests were performed after ICH. A MT-stabilizing agent, epothilone B (EpoB), was administered to explore the effects of MT stabilization on DA neurons and depression-like behavior after ICH. The results showed that obvious depression-like behavior occurred at 7, 14, and 28 days (P < 0.01) after ICH. These time-points were related to significant decreases in the concentration of DA (P < 0.01) and number of DA neurons (P < 0.01) in VTA. Moreover, The decrease of acetylated α-tubulin expression after ICH and Noco injection contributed to DA neurons' impairment in VTA, and Noco injecton also aggravate ICH-induced depression-like behaviors and DA neurons' injury. Furthermore, EpoB treatment significantly ameliorated ICH and Noco-induced depression-like behaviors (P < 0.05) and increased the concentration of DA (P < 0.05) and number of DA neurons (P < 0.05) in VTA by increasing the level of acetylated α-tubulin. The results indicate that EpoB can protect DA neurons by enhancing MT stability, and alleviate post-ICH depressive behaviors. This MT-targeted therapeutic strategy shows promise as a bench-to-bedside translational method for treating depression after ICH.
Insights
Intracerebral hemorrhage (ICH) causes depression-like behavior by damaging dopamine (DA) neurons. Maintaining microtubule (MT) stability with epothilone B (EpoB) protects DA neurons and alleviates these behaviors after ICH.
Area of Science:
- Neuroscience
- Pathophysiology
- Pharmacology
Background:
- Mesolimbic dopamine system dysfunction is crucial in depression.
- Reduced microtubule stability exacerbates brain injury, including intracerebral hemorrhage (ICH).
- Microtubule (MT) stability is vital for neuronal function, particularly in dopamine (DA) pathways.
Purpose of the Study:
- To investigate the occurrence of depression-like behavior after ICH.
- To determine if maintaining MT stabilization protects DA neurons in the ventral tegmental area (VTA).
- To assess if MT stabilization alleviates depression-like behavior post-ICH.
Main Methods:
- Mice underwent ICH induction via intrastriatal blood injection or nocodazole (Noco) administration.
- DA concentration, DA neuron count, and acetylated α-tubulin levels in the VTA were measured.
- Depression-related behaviors were assessed, and the MT-stabilizing agent epothilone B (EpoB) was administered.
Main Results:
- Depression-like behaviors manifested at 7, 14, and 28 days post-ICH, correlating with decreased VTA DA concentration and neuron numbers.
- ICH and Noco reduced acetylated α-tubulin, impairing VTA DA neurons and worsening depression-like behaviors.
- EpoB treatment significantly improved depression-like behaviors and increased VTA DA concentration and neuron counts by enhancing MT stability.
Conclusions:
- Microtubule stabilization is a promising therapeutic target for post-ICH depression.
- Epothilone B protects VTA DA neurons and mitigates depression-like behaviors by enhancing MT stability.
- This MT-targeted strategy offers a potential translational approach for treating depression following ICH.
Related Concept Videos
01:35Microtubules
01:18Microtubules
Microtubules have two structurally similar globular protein subunits: α and β tubulins. In the cytosol, the α and β tubulins form a heterodimer....
01:05Long-term Depression
03:12Freezing Point Depression and Boiling Point Elevation
The boiling point of a liquid is the temperature at which its vapor pressure is equal to ambient atmospheric pressure. Since the vapor pressure of a solution is lowered due to the presence of nonvolatile solutes, it stands to reason that the solution’s boiling point will subsequently be increased. Vapor pressure increases with temperature, and so a solution will require a higher temperature than will pure solvent to achieve any given vapor pressure, including one...
01:28Depressants
Alcohol is a common depressant that can induce a sense of relaxation and reduced inhibition at low doses. Contrary to its occasional...
01:18Depression: Overview